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Sample records for noradrenaline

  1. Dopamine versus noradrenaline in septic shock

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    Bo Xu

    2011-10-01

    Full Text Available BackgroundThe ‘Surviving Sepsis’ Campaign guidelines recommend theuse of dopamine or noradrenaline as the first vasopressor inseptic shock. However, information that guides clinicians inchoosing between dopamine and noradrenaline as the firstvasopressor in patients with septic shock is limited.ObjectiveThis article presents a review of the literature regarding theuse of dopamine versus noradrenaline in patients with septicshock.ResultsTwo randomised controlled trials (RCT and two largeprospective cohort studies were analysed. RCT data showeddopamine was associated with increased arrhythmic events.One cohort study found dopamine was associated with higher30-day mortality. The other cohort study found noradrenalinewas associated with higher 28-day mortality.DiscussionData on the use of dopamine versus noradrenaline in patientswith septic shock is limited. Following the recent SOAP IIstudy, there is now strong evidence that the use of dopaminein septic shock is associated with significantly morecardiovascular adverse events, compared tonoradrenaline.ConclusionNoradrenaline should be used as the initial vasopressor inseptic shock to avoid the arrhythmic events associatedwith dopamine.

  2. The distribution of 3H-(+-)noradrenaline in rabbit aortic strips after inhibition of the noradrenaline-metabolizing enzymes

    International Nuclear Information System (INIS)

    Henseling, M.; Eckert, E.; Trendelenburg, U.

    1976-01-01

    Rabbit aortic strips (nerve-free, reserpine pretreated or normal) whose noradrenaline-metabolizing enzymes were inhibited (by in vitro treatment with 0.5 mM pargyline for 30 min and by the presence of 0.1 mM U-0521) were exposed to 1.18 μM 3 H-(+-)noradrenaline for 30 min (in most experiments). At the end of the incubation some strips were used for anlysis of radioactivity (i.e., of noradrenaline and its metabolites), while for others the efflux of radioactivity was determined during 240 min of wash out with amine-free solution. An estimate of the original distribution of the amine into the various extraneuronal and neuronal compartments of the tissue was obtained by compartmental analysis of the efflux curves. Extracellular amine distributes into 'compartment I + II' (characterized by a half time for efflux of 14 C-sorbitol. The extraneuronal accumulation of noradrenaline is a quickly equilibrating process which involves compartments III and IV (with half times for efflux of 3 and 11 min, respectively). Compartment IV represents not only extraneuronally but also neuronally distributed noradrenaline. The neuronal accumulation of noradrenaline is a slowly equilibrating process which can be subdivided into axoplasmic and vesicular accumulation. The results support the view that the rate of relaxation (of strips initially exposed to noradrenaline and then washed out) is affected by the efflux of unchanged amine form extraneuronal and neuronal stores. (orig./GSE) [de

  3. Distribution of /sup 3/H-(+-)noradrenaline in rabbit aortic strips after inhibition of the noradrenaline-metabolizing enzymes

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    Henseling, M; Eckert, E; Trendelenburg, U [Wuerzburg Univ. (Germany, F.R.). Inst. fuer Pharmakologie und Toxikologie

    1976-01-01

    Rabbit aortic strips (nerve-free, reserpine pretreated or normal) whose noradrenaline-metabolizing enzymes were inhibited (by in vitro treatment with 0.5 mM pargyline for 30 min and by the presence of 0.1 mM U-0521) were exposed to 1.18 ..mu..M /sup 3/H-(+-)noradrenaline for 30 min (in most experiments). At the end of the incubation some strips were used for anlysis of radioactivity (i.e., of noradrenaline and its metabolites), while for others the efflux of radioactivity was determined during 240 min of wash out with amine-free solution. An estimate of the original distribution of the amine into the various extraneuronal and neuronal compartments of the tissue was obtained by compartmental analysis of the efflux curves. Extracellular amine distributes into 'compartment I + II' (characterized by a half time for efflux of < 1 min); compartment size and half time for efflux were similar to those obtained for /sup 14/C-sorbitol. The extraneuronal accumulation of noradrenaline is a quickly equilibrating process which involves compartments III and IV (with half times for efflux of 3 and 11 min, respectively). Compartment IV represents not only extraneuronally but also neuronally distributed noradrenaline. The neuronal accumulation of noradrenaline is a slowly equilibrating process which can be subdivided into axoplasmic and vesicular accumulation. The results support the view that the rate of relaxation (of strips initially exposed to noradrenaline and then washed out) is affected by the efflux of unchanged amine form extraneuronal and neuronal stores.

  4. Stereoselectivity of the distribution of labelled noradrenaline in rabbit aortic strips after inhibition of the noradrenaline-metabolizing enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Eckert, E; Henseling, M; Gescher, A; Trendelenburg, U [Wuerzburg Univ. (Germany, F.R.). Inst. fuer Pharmakologie und Toxikologie

    1976-01-01

    Rabbit aortic strips (nerve-free, reserpinepretreated or normal) whose noradrenaline-metabolizing enzymes were inhibited (by in vitro treatment with 0.5 mM pargyline for 30 min and by the presence of 0.1 mM U-0521) were exposed to 1.18 ..mu..M labelled (-)- or (+)noradrenaline for 30 min. At the end of the incubation period some strips were used for analysis of radioactivity (i.e., of noradrenaline and its metabolites), while for others the efflux of radioactivity was determined during 250 min of washout with amine-free solution. An estimate of the original distribution of the amine into the various extraneuronal and neuronal compartments of the tissue was obtained by compartmental analysis of the efflux curves. The mechanisms responsible for the accumulation of radioactivity in extraneuronal and axoplasmic compartments lack stereoselectivity; the rate constants for the efflux of radioactivity from these compartments are the same for (-)- and (+)noradrenaline. Despite the use of enzyme inhibitors, the 'late neuronal efflux' of radioactivity (i.e., the efflux collected between the 200th and 250th min of wash out) contained a considerable proportion of metabolites of noradrenaline. The metabolism of noradrenaline was stereoselective: while dihydroxyphenylglycol (DOPEG) was the predominant metabolite in the efflux from strips incubated with (-)noradrenaline, a considerable part of the efflux from strips incubated with the (+)isomer consisted of dihydroxymandelic acid and 'O-methylated and deaminated' metabolites (in addition to DOPEG).

  5. Stereoselectivity of the distribution of labelled noradrenaline in rabbit aortic strips after inhibition of the noradrenaline-metabolizing enzymes

    International Nuclear Information System (INIS)

    Eckert, E.; Henseling, M.; Gescher, A.; Trendelenburg, U.

    1976-01-01

    Rabbit aortic strips (nerve-free, reserpinepretreated or normal) whose noradrenaline-metabolizing enzymes were inhibited (by in vitro treatment with 0.5 mM pargyline for 30 min and by the presence of 0.1 mM U-0521) were exposed to 1.18 μM labelled (-)- or (+)noradrenaline for 30 min. At the end of the incubation period some strips were used for analysis of radioactivity (i.e., of noradrenaline and its metabolites), while for others the efflux of radioactivity was determined during 250 min of washout with amine-free solution. An estimate of the original distribution of the amine into the various extraneuronal and neuronal compartments of the tissue was obtained by compartmental analysis of the efflux curves. The mechanisms responsible for the accumulation of radioactivity in extraneuronal and axoplasmic compartments lack stereoselectivity; the rate constants for the efflux of radioactivity from these compartments are the same for (-)- and (+)noradrenaline. Despite the use of enzyme inhibitors, the 'late neuronal efflux' of radioactivity (i.e., the efflux collected between the 200th and 250th min of wash out) contained a considerable proportion of metabolites of noradrenaline. The metabolism of noradrenaline was stereoselective: while dihydroxyphenylglycol (DOPEG) was the predominant metabolite in the efflux from strips incubated with (-)noradrenaline, a considerable part of the efflux from strips incubated with the (+)isomer consisted of dihydroxymandelic acid and 'O-methylated and deaminated' metabolites (in addition to DOPEG). (orig/GSE) [de

  6. Plasma clearance of noradrenaline does not change with age in normal subjects

    DEFF Research Database (Denmark)

    Hilsted, J; Christensen, N J; Larsen, S

    1985-01-01

    Noradrenaline kinetics (plasma concentrations, plasma clearance and appearance rates) were investigated in seven elderly healthy subjects and in six young healthy subjects. Forearm venous plasma noradrenaline concentrations were higher in the elderly subjects compared with the young subjects. Pla....... Plasma clearance of noradrenaline was identical in the two groups. The increase in plasma noradrenaline concentration, with age, probably reflects an increased sympathetic nervous activity.......Noradrenaline kinetics (plasma concentrations, plasma clearance and appearance rates) were investigated in seven elderly healthy subjects and in six young healthy subjects. Forearm venous plasma noradrenaline concentrations were higher in the elderly subjects compared with the young subjects...

  7. Leptin inhibits and ghrelin augments hypothalamic noradrenaline release after stress.

    Science.gov (United States)

    Kawakami, Akio; Okada, Nobukazu; Rokkaku, Kumiko; Honda, Kazufumi; Ishibashi, Shun; Onaka, Tatsushi

    2008-09-01

    Metabolic conditions affect hypothalamo-pituitary-adrenal responses to stressful stimuli. Here we examined effects of food deprivation, leptin and ghrelin upon noradrenaline release in the hypothalamic paraventricular nucleus (PVN) and plasma adrenocorticotropic hormone (ACTH) concentrations after stressful stimuli. Food deprivation augmented both noradrenaline release in the PVN and the increase in plasma ACTH concentration following electrical footshocks (FSs). An intracerebroventricular injection of leptin attenuated the increases in hypothalamic noradrenaline release and plasma ACTH concentrations after FSs, while ghrelin augmented these responses. These data suggest that leptin inhibits and ghrelin facilitates neuroendocrine stress responses via noradrenaline release and indicate that a decrease in leptin and an increase in ghrelin release after food deprivation might contribute to augmentation of stress-induced ACTH release in a fasting state.

  8. Adeprene influence on the turnover rate of brain noradrenaline

    International Nuclear Information System (INIS)

    Tyutyulkova, N.I.; Gorancheva, J.I.; Ankov, V.K.

    1978-01-01

    The influence of Adeprene - Bulgarian antidepressant - on the content and the turnover rate of the rat brain noradrenaline was studied. The animals were injected intraperitoneally during 5 days with 20 mg/kg Adeprene. One hour after the last administration of Adeprene, Tyrosine, labelled with 14 C was injected. The animals were sacrified on the 1st, 2nd and 4th hours after the injection of 14 C-Tyrosine. The tyrosine and noradrenaline concentration were determined spectrofluorimetrically the concentration of the compounds labelled with 14 C by means of a liquid scintillator. The turnover rate constant of noradrenaline was calculated on the basis of the obtained results and the respective formula. It was established that under the influence of Adeprene, the noradrenaline concentration in the brain rises from 0,5 g/g in the control animals to 0,6 in treated mice. The turnover rate constant of noradrenaline, however, drops to 0,9 g/g/hour as compared to 0,15 g/g/hours in the controls. The determination of the turnover rate provides an idea about the intensity of utilization and synthesis of the mediator and is considered consequently as a more radiosensitive index for the neuronal activity then the total amine content. (A.B.)

  9. Attempt to separate the fluorescence spectra of adrenaline and noradrenaline using chemometrics

    DEFF Research Database (Denmark)

    Nikolajsen, Rikke P; Hansen, Åse Marie; Bro, R

    2000-01-01

    An investigation was conducted on whether the fluorescence spectra of the very similar catecholamines adrenaline and noradrenaline could be separated using chemometric methods. The fluorescence landscapes (several excitation and emission spectra were measured) of two data sets with respectively 16...... regression (Unfold-PLSR) on the larger data set and parallel factor analysis (PARAFAC) of the six samples of the smaller set showed that there was no difference between the fluorescence landscapes of adrenaline and noradrenaline. It can be concluded that chemometric separation of adrenaline and noradrenaline...

  10. Muscarinic receptors in separate populations of noradrenaline- and adrenaline-containing chromaffin cells

    International Nuclear Information System (INIS)

    Michelena, P.; Moro, M.A.; Castillo, C.J.; Garcia, A.G.

    1991-01-01

    We have performed binding experiments of (a)[3H]quinuclidinyl benzilate to partially purified membranes from noradrenaline- and adrenaline-containing chromaffin cells and (b) [3H]N-methyl-quinuclidinyl benzilate to acutely isolated, or 48-h cultured, chromaffin cells subpopulations. Using this approach, we obtained enough evidence to conclude (1st) that muscarinic receptors are present in both noradrenaline- and adrenaline containing cells; (2nd) that noradrenaline cells contain in fact 2-3 fold higher density of those receptors; and (3rd) that those receptors undergo plastic changes upon chronic culturing of the cells

  11. Exposure of P. gingivalis to noradrenaline reduces bacterial growth and elevates ArgX protease activity.

    Science.gov (United States)

    Saito, Takayuki; Inagaki, Satoru; Sakurai, Kaoru; Okuda, Katsuji; Ishihara, Kazuyuki

    2011-03-01

    Periodontitis, an infectious disease caused by periodontopathic bacteria, including Porphyromonas gingivalis, is reported to be accelerated by stress, under which noradrenaline levels are increased in the bloodstream. The purpose of this study was to evaluate the effects of noradrenaline on P. gingivalis. P. gingivalis was incubated in the presence of 25μM, 50μM, or 100μM adrenaline or noradrenaline at 37°C for 12, 24 or 36h and growth was evaluated by OD(660). Auto-inducer-2 (AI-2) was measured by luminescence of Vibrio harveyi BB 170. Expression of P. gingivalis genes was evaluated using a microarray and RT-PCR. Rgp activity of arg-gingipainA and B (Rgp) was measured with a synthetic substrate. Growth of P. gingivalis FDC381 was inhibited by noradrenaline at 24 and 36h. Growth inhibition by noradrenaline increased dose-dependently. Inhibition of growth partially recovered with addition of propranolol. AI-2 production from P. gingivalis showed a marked decrease with addition of noradrenaline compared with peak production levels in the control group. Microarray analysis revealed an increase in expression in 18 genes and a decrease in expression in 2 genes. Amongst these genes, expression of the protease arg-gingipainB (RgpB) gene, a major virulence factor of P. gingivalis, was further analysed. Expression of rgpB showed a significant increase with addition of noradrenaline, which was partially reduced by addition of propranolol. Cell-associated Rgp activity also increased with addition of noradrenaline. These results suggest that stressors influence the expression of the virulence factors of P. gingivalis via noradrenaline. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Effect of noradrenaline on production of methoxyindoles by rat pineal gland in organ culture

    International Nuclear Information System (INIS)

    Morton, D.J.

    1987-01-01

    This report examined the effect of noradrenaline on production of methoxyindoles by the pineal gland in organ culture. Pineal glands were incubated in pairs in 95μl culture medium containing 5-hydroxy [2- 14 C]tryptamine creatinine sulphate (0,1 mM) and noradrenaline (NA) (0,5-100 μM). The results indicated that noradrenaline appeared to have a characteristic action on pineal metabolism. An increase in production of both N-acetylserotonin and melatonin by the pineal after noradrenaline treatment was observed. The overall production of methoxyindoles followed a very similar trend to that of N-acetylserotonin and melatonin, which suggests some degree of noradrenergic control over HIOMT levels

  13. Noradrenaline and isoproterenol kinetics in diabetic patients with and without autonomic neuropathy

    DEFF Research Database (Denmark)

    Dejgaard, Anders; Hilsted, J; Christensen, N J

    1986-01-01

    Noradrenaline and isoproterenol kinetics using intravenous infusion of L-3H-NA and of 3H-isoproterenol were investigated in eight Type 1 (insulin-dependent) diabetic patients without neuropathy and in eight Type 1 diabetic patients with autonomic neuropathy matched for age, sex and duration...... with autonomic failure (p less than 0.01). The disappearance of L-3H-noradrenaline from plasma after the infusion of L-3H-noradrenaline had been stopped was not different in patients with and without neuropathy. The metabolic clearance of isoproterenol was not influenced by the presence of autonomic failure...

  14. Rotational Spectra of Adrenaline and Noradrenaline

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    Cortijo, V.; López, J. C.; Alonso, J. L.

    2009-06-01

    The emergence of Laser Ablation Molecular Beam Fourier Transform Microwave (LA-MB-FTMW) spectroscopy has rendered accessible the gas-phase study of solid biomolecules with high melting points. Among the biomolecules to benefit from this technique, neurotransmitters have received special attention due to the lack of experimental information and their biological relevance. As a continuation of the we present the study of adrenaline and noradrenaline. The comparison between the experimental rotational and ^{14}N nuclear quadrupole coupling constants and those calculated ab initio provide a definitive test for molecular structures and confirm unambiguously the identification of four conformers of adrenaline and three conformers of noradrenaline. Their relative population in the jet has been evaluated by relative intensity measurements of selected rotational transitions. The most abundant conformer in both neurotransmitters present an extended AG configuration with a O-H\\cdotsN hydrogen bond in the side chain. J.L. Alonso, M.E. Sanz, J.C. López and V. Cortijo, J. Am. Chem. Soc. (in press), 2009

  15. Serotonin and noradrenaline reuptake inhibitors improve micturition control in mice.

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    Marco Redaelli

    Full Text Available Poor micturition control may cause profound distress, because proper voiding is mandatory for an active social life. Micturition results from the subtle interplay of central and peripheral components. It involves the coordination of autonomic and neuromuscular activity at the brainstem level, under the executive control of the prefrontal cortex. We tested the hypothesis that administration of molecules acting as reuptake inhibitors of serotonin, noradrenaline or both may exert a strong effect on the control of urine release, in a mouse model of overactive bladder. Mice were injected with cyclophosphamide (40 mg/kg, to increase micturition acts. Mice were then given one of four molecules: the serotonin reuptake inhibitor imipramine, its metabolite desipramine that acts on noradrenaline reuptake, the serotonin and noradrenaline reuptake inhibitor duloxetine or its active metabolite 4-hydroxy-duloxetine. Cyclophosphamide increased urine release without inducing overt toxicity or inflammation, except for increase in urothelium thickness. All the antidepressants were able to decrease the cyclophosphamide effects, as apparent from longer latency to the first micturition act, decreased number of urine spots and volume of released urine. These results suggest that serotonin and noradrenaline reuptake inhibitors exert a strong and effective modulatory effect on the control of urine release and prompt to additional studies on their central effects on brain areas involved in the social and behavioral control of micturition.

  16. Correlations between plasma noradrenaline concentrations, antioxidants, and neutrophil counts after submaximal resistance exercise in men

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    Ramel, A; Wagner, K; Elmadfa, I

    2004-01-01

    Objectives: To investigate noradrenaline concentrations, neutrophil counts, plasma antioxidants, and lipid oxidation products before and after acute resistance exercise. Methods: 17 male participants undertook a submaximal resistance exercise circuit (10 exercises; 75% of the one repetition maximum; mean (SD) exercise time, 18.6 (1.1) minutes). Blood samples were taken before and immediately after exercise and analysed for plasma antioxidants, noradrenaline, neutrophils, and lipid oxidation products. Wilcoxon's signed-rank test and Pearson's correlation coefficient were used for calculations. Results: Neutrophils, noradrenaline, fat soluble antioxidants, and lipid oxidation products increased after exercise. Noradrenaline concentrations were associated with higher antioxidant concentrations. Neutrophils were related to higher concentrations of conjugated dienes. Conclusions: Submaximal resistance exercise increases plasma antioxidants. This might reflect enhanced antioxidant defence in response to the oxidative stress of exercise, though this is not efficient for inhibiting lipid oxidation. The correlation between noradrenaline concentrations and plasma antioxidants suggests a modulating role of the stress hormone. Neutrophils are a possible source of oxidative stress after resistance exercise. PMID:15388566

  17. [Features of noradrenaline stimulation of rat liver mitochondria respiration by ADP and calcium ions].

    Science.gov (United States)

    Stefankiv, Iu S; Babskyĭ, A M; Shostakovska, Y V

    1995-01-01

    A single administration of a physiological dose of noradrenaline to animals. in contrast to adrenaline, stimulates the respiration of mitochondria not only under oxidation of FAD-dependent Krebbs cycle substrate of the succinase but also HAD-dependent substrate of alpha-ketoglutarate. In the both cases the phosphorylation rate increases, since the action of noradrenaline, separating the respiration and oxidative phosphorylation, was not found. Noradrenaline increases the capacity of mitochondria to more actively absorb calcium ions under oxidation of succinate than under that of alpha-ketoglutarate.

  18. Reduced plasma noradrenaline during angiotensin II-induced acute hypertension in man

    DEFF Research Database (Denmark)

    Henriksen, J H; Kastrup, J; Christensen, N J

    1985-01-01

    1. Plasma noradrenaline and adrenaline concentrations were measured in ten subjects before, during and after intravenous infusion of angiotensin II (ANG II) in order to determine the sympathoadrenal response of ANG II challenge in man. In five subjects ganglionic blockade was additionally performed...... by intravenous infusion of trimethaphan. 2. During ANG II infusion mean arterial blood pressure increased by 30% (P adrenaline decreased less. 3. During ganglionic blockade plasma noradrenaline decreased significantly (P

  19. Effects of propofol and sevoflurane on isolated human umbilical arteries pre-contracted with dopamine, adrenaline and noradrenaline.

    Science.gov (United States)

    Gunduz, Ergun; Arun, Oguzhan; Bagci, Sengal Taylan; Oc, Bahar; Salman, Alper; Yilmaz, Setenay Arzu; Celik, Cetin; Duman, Ates

    2015-05-01

    To assess the effects of propofol and sevoflurane on the contraction elicited by dopamine, adrenaline and noradrenaline on isolated human umbilical arteries. Umbilical arteries were cut into endothelium-denuded spiral strips and suspended in organ baths containing Krebs-Henseleit solution bubbled with O2 +CO2 mixture. Control contraction to phenylephrine (10(-5)  M) was recorded. Response curves were obtained to 10(-5)  M dopamine, 10(-5)  M adrenaline or 10(-5)  M noradrenaline. Afterwards, either cumulative propofol (10(-6)  M, 10(-5)  M and 10(-4)  M) or cumulative sevoflurane (1.2%, 2.4% and 3.6%) was added to the organ bath, and the responses were recorded. Responses are expressed percentage of phenylephrine-induced contraction (mean ± standard deviation) (P adrenaline and noradrenaline (P adrenaline. High and highest concentrations of sevoflurane caused significantly higher relaxation compared with the high and highest concentrations of propofol on the contraction elicited by noradrenaline. Dopamine, adrenaline and noradrenaline elicit contractions in human umbilical arteries, and noradrenaline causes the highest contraction. Both propofol and sevoflurane inhibit these contractions in a dose-dependent manner. Propofol caused greater relaxation in the contractions elicited by dopamine and adrenaline while sevoflurane caused greater relaxation in the contraction elicited by noradrenaline. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  20. The Dynamic cerebral autoregulatory adaptive response to noradrenaline is attenuated during systemic inflammation in humans

    DEFF Research Database (Denmark)

    Berg, Ronan M. G.; Plovsing, Ronni R.; Bailey, Damian M.

    2015-01-01

    Vasopressor support is used widely for maintaining vital organ perfusion pressure in septic shock, with implications for dynamic cerebral autoregulation (dCA). This study investigated whether a noradrenaline-induced steady state increase in mean arterial blood pressure (MAP) would enhance d......, noradrenaline administration was associated with a decrease in gain (1.18 (1.12-1.35) vs 0.93 (0.87-0.97) cm/mmHg per s; P vs 0.94 (0.81-1.10) radians; P = 0.58). After LPS, noradrenaline administration changed neither gain (0.91 (0.85-1.01) vs 0.87 (0.......81-0.97) cm/mmHg per s; P = 0.46) nor phase (1.10 (1.04-1.30) vs 1.37 (1.23-1.51) radians; P = 0.64). The improvement of dCA to a steady state increase in MAP is attenuated during an LPS-induced systemic inflammatory response. This may suggest that vasopressor treatment with noradrenaline offers no additional...

  1. [3H] glycogen hydrolysis in brain slices: responses to meurotransmitters and modulation of noradrenaline receptors

    International Nuclear Information System (INIS)

    Quach, T.T.; Rose, C.; Schwartz, J.C.

    1978-01-01

    Different agents have been investigated for their effects on [ 3 H] glycogen synthesized in mouse cortical slices. Of these noradrenaline, serotonin and histamine induced clear concentration-dependent glycogenesis. [ 3 H] glycogen hydrolysis induced by noradrenaline appears to be mediated by beta-adrenergic receptors because it is completely prevented by timolol, while phentolamine is ineffective. It seems to involve cyclic AMP because it is potentiated in the presence of isobutylmethylxanthine; in addition dibutyryl cyclic AMP (but not dibutyryl cyclic GMP) promotes glycogenolysis. Lower concentrations of noradrenaline were necessary for [ 3 H] glycogen hydrolysis (ECsub(50) 0.5μM) than for stimulation of cyclic AMP accumulation (ECsub(50) = 8μM). After subchronic reserpine treatment the concentration-response curve to noradrenaline was significantly shifted to the left (ECsub(50) = 0.09 +- 0.02 μM as compared with 0.49 +- 0.08μM in saline-pretreated mice) without modifications of either the basal [ 3 H] glycogen level, maximal glycogenolytic effect, or the dibutyryl cAMP-induced glycogenolytic response. In addition to noradrenaline, clear concentration-dependent [ 3 H] glycogen hydrolysis was observed in the presence of histamine or serotonin. In contrast to the partial [ 3 H] glycogen hydrolysis elicited by these biogenic amines, depolarization of the slices by 50 mM K + provoked a nearly total [ 3 H] glycogen hydrolysis. (author)

  2. The release of noradrenaline in the locus coeruleus and prefrontal cortex studied with dual-probe microdialysis

    NARCIS (Netherlands)

    Pudovkina, O; Kawahara, Y; de Vries, J.B; Westerink, B.H.C.

    2001-01-01

    The present study was undertaken to investigate and compare the properties of noradrenaline release in the locus coeruleus (LC) and prefrontal cortex (PFC). For that aim the dual-probe microdialysis technique was applied for simultaneous detection of noradrenaline levels in the LC and PFC in

  3. Modulation of sibutramine-induced increases in extracellular noradrenaline concentration in rat frontal cortex and hypothalamus by α2-adrenoceptors

    Science.gov (United States)

    Wortley, K E; Heal, D J; Stanford, S C

    1999-01-01

    The effects of sibutramine (0.25–10 mg kg−1 i.p.) on extracellular noradrenaline concentration in the frontal cortex and hypothalamus of freely-moving rats were investigated using microdialysis. The role of presynaptic α2-adrenoceptors in modulating the effects of sibutramine in these brain areas was also determined.Sibutramine induced an increase in extracellular noradrenaline concentration, the magnitude of which paralleled dose, in both brain areas. In the cortex, this increase was gradual and sustained, whereas in the hypothalamus it was more rapid and of shorter duration.In both the cortex and hypothalamus, pretreatment of rats with the α2-adrenoceptor antagonist RX821002 (3 mg kg−1 i.p.) potentiated increases in the accumulation of extracellular noradrenaline induced by sibutramine (10 mg kg−1 i.p.), by 7 and 10 fold respectively. RX821002 also reduced the latency of sibutramine to reach its maximum effect in the cortex, but not in the hypothalamus.Infusion of RX821002 (1 μM) via the probe increased the accumulation of extracellular noradrenaline induced by sibutramine (10 mg kg−1 i.p.) in both brain areas. In the hypothalamus, the effects of RX821002 on the accumulation of noradrenaline induced by sibutramine were 2 fold greater than those in the cortex.These findings support evidence that sibutramine inhibits the reuptake of noradrenaline in vivo, but that the accumulation of extracellular noradrenaline is limited by noradrenergic activation of presynaptic α2-adrenoceptors. Furthermore, the data suggest that terminal α2-adrenoceptors in the hypothalamus exert a greater inhibitory effect over the control of extracellular noradrenaline accumulation than do those in the cortex. PMID:10516646

  4. Response Surface Modelling of Noradrenaline Production in Hairy Root Culture of Purslane (Portulaca oleracea L.

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    Mehdi Ghorbani

    2015-03-01

    Full Text Available Common purslane (Portulaca oleracea L. is an annual plant as one of the natural sources for noradrenaline hormone. In this research, hairy root culture of purslane was established by using Agrobacterium rhizogenes strain ATCC 15834. In the following, Box-Behnken model of response surface methodology (RSM was employed to optimize B5 medium for the growth of P. oleracea L. hairy root line. According to the results, modelling and optimization conditions, including sucrose, CaCl2.H2O, H2PO4 and NO3-/NH4+ concentrations on maximum dry weight (0.155 g and noradrenaline content (0.36 mg.g-1 DW was predicted. These optimal conditions predicted by RSM were confirmed the enhancement of noradrenaline production as an application potential for production by hairy root cultures.

  5. Role of adrenal hormones in the synthesis of noradrenaline in cardiac sympathetic neurones

    Science.gov (United States)

    Bhagat, B.

    1969-01-01

    1. Adrenalectomy or adrenal demedullation affected neither the levels of endogenous catecholamines in the rat heart nor the accumulation of 3H-noradrenaline 1 hr after its intravenous administration. 2. Twenty-four hours after intravenous administration of labelled amine, however, its retention was markedly reduced in the heart of adrenalectomized or demedullated rats. Ganglionic blockade prevented this reduction. 3. Rate calculations from the decline of catecholamine levels after blockade of synthesis with α-methyl-tyrosine showed that cardiac synthesis of noradrenaline increased about four-fold after demedullation and about three-fold after adrenalectomy. This increase in synthesis may compensate for the loss of circulating catecholamines. 4. There was no change in catechol-o-methyl-transferase activity, but monoamine oxidase activity was increased in the homogenates of the heart of adrenalectomized and demedullated rats. The increase in the cardiac monoamine oxidase activity was markedly greater in the adrenalectomized rats than in the demedullated rats. 5. It is suggested that adrenal cortex insufficiency may modulate the rate of synthesis of noradrenaline and monoamine oxidase activity in cardiac sympathetic neurones. PMID:5360339

  6. TERLIPRESSIN VERSUS NORADRENALINE FOR HEPATORENAL SYNDROME. Economic evaluation under the perspective of the Brazilian Public Health System

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    Ângelo Zambam de MATTOS

    Full Text Available ABSTRACT Background - Terlipressin and noradrenaline are the best studied treatments for hepatorenal syndrome, and there is no evidence of superiority of one over the other regarding to efficacy. While the former drug is more costly, the latter requires admission into an intensive care unit. Objective - The aim of this study was to perform an economic evaluation, comparing treatments for hepatorenal syndrome with terlipressin and noradrenaline. Methods - For the economic evaluation, a cost-minimization analysis was performed. Direct medical costs of the two treatment strategies were compared under the perspective of the Brazilian Public Health System as the third-party payer. A probabilistic sensitivity analysis was performed. Results - The costs of treatments with terlipressin or noradrenaline were 287.77 and 2,960.45 International Dollars (Int$ respectively. Treatment using terlipressin would save Int$2,672.68 for the Public Health System for each hospital admission related to hepatorenal syndrome. In the probabilistic sensitivity analysis, it was verified that the cost of the treatment with noradrenaline could vary between Int$2,326.53 and Int$3,644.16, while costs related to the treatment using terlipressin are not variable. Conclusion - The treatment strategy using terlipressin was more economical than that using noradrenaline under the perspective of the Brazilian Public Health System as the third-party payer.

  7. Contrasting Roles of Dopamine and Noradrenaline in the Motivational Properties of Social Play Behavior in Rats.

    Science.gov (United States)

    Achterberg, E J Marijke; van Kerkhof, Linda W M; Servadio, Michela; van Swieten, Maaike M H; Houwing, Danielle J; Aalderink, Mandy; Driel, Nina V; Trezza, Viviana; Vanderschuren, Louk J M J

    2016-02-01

    Social play behavior, abundant in the young of most mammalian species, is thought to be important for social and cognitive development. Social play is highly rewarding, and as such, the expression of social play depends on its pleasurable and motivational properties. Since the motivational properties of social play have only sporadically been investigated, we developed a setup in which rats responded for social play under a progressive ratio schedule of reinforcement. Dopaminergic neurotransmission plays a key role in incentive motivational processes, and both dopamine and noradrenaline have been implicated in the modulation of social play behavior. Therefore, we investigated the role of dopamine and noradrenaline in the motivation for social play. Treatment with the psychostimulant drugs methylphenidate and cocaine increased responding for social play, but suppressed its expression during reinforced play periods. The dopamine reuptake inhibitor GBR-12909 increased responding for social play, but did not affect its expression, whereas the noradrenaline reuptake inhibitor atomoxetine decreased responding for social play as well as its expression. The effects of methylphenidate and cocaine on responding for social play, but not their play-suppressant effects, were blocked by pretreatment with the dopamine receptor antagonist α-flupenthixol. In contrast, pretreatment with the α2-adrenoceptor antagonist RX821002 prevented the play-suppressant effect of methylphenidate, but left its effect on responding for social play unaltered. In sum, the present study introduces a novel method to study the incentive motivational properties of social play behavior in rats. Using this paradigm, we demonstrate dissociable roles for dopamine and noradrenaline in social play behavior: dopamine stimulates the motivation for social play, whereas noradrenaline negatively modulates the motivation for social play behavior and its expression.

  8. Food-dependent exercise-induced anaphylaxis with a high level of plasma noradrenaline.

    Science.gov (United States)

    Kato, Yukihiko; Nagai, Ayako; Saito, Masuyoshi; Ito, Tomonobu; Koga, Michiyuki; Tsuboi, Ryoji

    2007-02-01

    Ingesting certain foods sometimes triggers anaphylaxis when followed by exercise (food-dependent exercise-induced anaphylaxis, FDEIA). Specific food-induced mucocutaneous urticaria may also progress to anaphylaxis (oral allergy syndrome, OAS). A positive skin test and/or radioallergosorbent test (RAST) to the foods suggest involvement of immunoglobulin (Ig)E-anaphylaxis in both disorders. The triggering foods and initial target organs are usually different in each case. In the present study, a 32-year-old male reported dyspnea accompanied by wheals, and symptoms of low blood pressure while walking after eating Chinese noodles and donuts. He also reported uncomfortable sensations in his mouth and throat after ingesting melon. Exercise challenge tests were administered. Serum histamine, plasma adrenaline, noradrenaline and dopamine were measured pre- and post-test. No symptoms were induced by exercise or by the ingestion of any single food item before exercise. However, numerous wheals appeared when exercise followed the combined ingestion of foods. Likewise, the sequence of eating pancakes and then exercising resulted in numerous wheals and anaphylaxis. Olopatadine hydrochloride and ketotifen fumarate completely inhibited this anaphylaxis. The skin prick tests resulted in fruit-induced erythema and wheals. The results of these tests with wheat, butter and sugar were negative, and no symptoms were induced by the exercise test after ingestion of watermelon, melon or apple. The anaphylactoid symptoms were accompanied by a significant increase of plasma noradrenaline. In this case, not only wheat, but sugar and butter may induce the onset of FDEIA. There was no significant correlation between the intensity of the symptoms and the serum histamine levels in the present case. Noradrenaline may be involved in the onset of FDEIA, since noradrenaline may selectively inhibit T-helper (Th)1 functions while favoring Th2 responses. The tests showed no cross-reactivity between the

  9. Adrenaline but not noradrenaline is a determinant of exercise-induced lipid mobilization in human subcutaneous adipose tissue

    DEFF Research Database (Denmark)

    Glisezinski, I. de; Larrouy, D.; Bajzova, M.

    2009-01-01

    The relative contribution of noradrenaline (norepinephrine) and adrenaline (epinephrine) in the control of lipid mobilization in subcutaneous adipose tissue (SCAT) during exercise was evaluated in men treated with a somatostatin analogue, octreotide. Eight lean and eight obese young men matched...... of octreotide suppressed plasma insulin and growth hormone levels at rest and during exercise. It blocked the exercise-induced increase in plasma adrenaline while that of noradrenaline was unchanged. Plasma natriuretic peptides (NPs) level was higher at rest and during exercise under octreotide infusion in lean...... individuals. In conclusion, blockade of beta-adrenergic receptors during exercise performed during infusion of octreotide (blocking the exercise-induced rise in adrenaline but not that of noradrenaline) does not alter the exercise-induced lipolysis. This suggests that adrenaline is the main adrenergic agent...

  10. Comparison of changes in the extracellular concentration of noradrenaline in rat frontal cortex induced by sibutramine or d-amphetamine: modulation by α2-adrenoceptors

    Science.gov (United States)

    Wortley, K E; Hughes, Z A; Heal, D J; Stanford, S C

    1999-01-01

    The effects of sibutramine (0.25–10 mg kg−1, i.p.) on extracellular noradrenaline concentration in the frontal cortex of halothane-anaesthetized rats were compared with those of d-amphetamine (1–3 mg kg−1, i.p.) using in vivo microdialysis. The role of presynaptic α2-adrenoceptors in modulating the effects of these drugs on extracellular noradrenaline concentration were also investigated by pretreating rats with the selective α2-adrenoceptor antagonist, RX821002.Sibutramine induced a gradual and sustained increase in extracellular noradrenaline concentration. The dose-response relationship was described by a bell-shaped curve with a maximum effect at 0.5 mg kg−1. In contrast, d-amphetamine induced a rapid increase in extracellular noradrenaline concentration, the magnitude of which paralleled drug dose.Pretreatment with the α2-adrenoceptor antagonist, RX821002 (dose 3 mg kg−1, i.p.) increased by 5 fold the accumulation of extracellular noradrenaline caused by sibutramine (10 mg kg−1) and reduced the latency of sibutramine to reach its maximum effect from 144–56 min.RX821002-pretreatment increased by only 2.5 fold the increase in extracellular noradrenaline concentration caused by d-amphetamine alone (10 mg kg−1) and had no effect on the latency to reach maximum.These findings support evidence that sibutramine acts as a noradrenaline uptake inhibitor in vivo and that the effects of this drug are blunted by indirect activation of presynaptic α2-adreno-ceptors. In contrast, the rapid increase in extracellular noradrenaline concentration induced by d-amphetamine is consistent with this being mainly due to an increase in Ca2+-independent release of noradrenaline. PMID:10482917

  11. The neuropharmacology of serotonin and noradrenaline in depression.

    Science.gov (United States)

    Nutt, David J

    2002-06-01

    Several classes of antidepressant drug exist, divided into three broad families, the monoamine reuptake inhibitors, the monoamine oxidase inhibitors and the monoamine receptor antagonists. All these drugs have a common pharmacological effect, to raise the synaptic concentrations of noradrenaline and serotonin. Although different drugs have different relative selectivity for noradrenaline and serotonin systems, these two neurotransmitter pathways work in parallel and in a coherent manner to produce the same final antidepressant response. The lag-time in the onset of action of antidepressants can be explained by the activation of inhibitory autoreceptors on serotonergic and noradrenergic neurones which initially attenuate the effects of antidepressants on synaptic transmitter levels. Over time, these autoreceptors desensitize, allowing the emergence of an overt antidepressant response. This theory has led to the proposition that antagonists at these autoreceptors such as pindolol may be useful adjuncts to antidepressant treatment, in order to hasten the appearance of a clinical response. Evidence for the clinical validity of this idea remains equivocal, however. The use of central monoamine depletion studies has demonstrated that it is elevated synaptic monoamine levels themselves, rather than some downstream postsynaptic changes in, for example, receptor sensitivity, that are responsible for the therapeutic effect of antidepressant drugs. Taken together, the data collected over the last 40 years have allowed the emergence of a unified monoamine hypothesis of antidepressant drug action.

  12. Comparative evaluation of two radioenzymatic procedures designed to determine noradrenaline in the plasma (COMT assay and PNMT assay)

    International Nuclear Information System (INIS)

    Barth, A.

    1984-01-01

    A comparative evaluation of two radioenzymatic procedures to determine the concentration of noradrenaline in the plasma - with linearity, sensitivity, specifity and accuracy serving as test criteria - led to the following results: In view of a probability of error in the order of 2% both methods were judged to show a satisfactory sensitivity. The specific of the COMT assay, by contrast with that of the PNMT assay, was found to be wanting, as the noradrenaline measurements in the presence of other biogenic amines were biassed in such a way that the values determined were higher than the actual concentrations. During antihypertensive treatment even minimal changes in the noradrenaline concentration can be ascertained on a quantitative basis. If suitable hardware is available, the COMT assay permits up to 25 single determinations to be carried out per day, while the number of double determinations is restricted to 7 per day. One advantage, however, lies in the fact that several catecholamines in the plasma can be detected simultaneously, if required. In cases where the noradrenaline concentration alone is to be determined for clinical purposes, preference should be given to the PNMT assay, as both tests showed equal linearity and sensitivity. (TRV) [de

  13. [The effect of prolonged treatment of hypertensive rats with antihypertensive drugs of various actions on the arterial tension and noradrenaline level in the myocardium, brain and aortal].

    Science.gov (United States)

    Kiriakov, A; Khlebarova, M; Staneva-stoicheva, D; Panova, I

    1975-01-01

    The authors examined the changes in arterial blood pressure and the content of Noradrenaline in the myocardium, brain and aorta of rats with hypertension due to nephrectomy and treatment with desoxycorticosterone and NaCl, and after a chronic 6-month treatment of hypertension with various antihypertensive means. The most significant reduction of noradrenaline in the three of the examined tissues was found in rats, which received dic. sulfyram (100 mg/kg per os). Clondine (10 mkg/kg, per os) manifested the strongest hypotensive effect and lowered the level of noradrenaline in the myocardium, while it was raised in the aorta. Reserpine (10 mkg/kg, s. c) induced a clear reduction of Noradrenaline content in the brain, but an increase in the other two tissues. Insignificant hypotensive effect was observed in animals, treated with guanetidine (0.5 mg/kg, per os), which did not affect substantially noradrenaline in the examined organs. The increase of noradrenaline level was established in the three of the organs of animals, treated with alpha-methyl-DOFA (25 mg/kg, per os). Furosemide (1 mg/kg, s.c.) induced a statistically significant elevation of noradrenaline in the aorta, but was noneffective to noradrenaline in the myocardium and brain.

  14. Antidepressant drugs specifically inhibiting noradrenaline reuptake enhance recognition memory in rats.

    Science.gov (United States)

    Feltmann, Kristin; Konradsson-Geuken, Åsa; De Bundel, Dimitri; Lindskog, Maria; Schilström, Björn

    2015-12-01

    Patients suffering from major depression often experience memory deficits even after the remission of mood symptoms, and many antidepressant drugs do not affect, or impair, memory in animals and humans. However, some antidepressant drugs, after a single dose, enhance cognition in humans (Harmer et al., 2009). To compare different classes of antidepressant drugs for their potential as memory enhancers, we used a version of the novel object recognition task in which rats spontaneously forget objects 24 hr after their presentation. Antidepressant drugs were injected systemically 30 min before or directly after the training phase (Session 1 [S1]). Post-S1 injections were used to test for specific memory-consolidation effects. The noradrenaline reuptake inhibitors reboxetine and atomoxetine, as well as the serotonin noradrenaline reuptake inhibitor duloxetine, injected prior to S1 significantly enhanced recognition memory. In contrast, the serotonin reuptake inhibitors citalopram and paroxetine and the cyclic antidepressant drugs desipramine and mianserin did not enhance recognition memory. Post-S1 injection of either reboxetine or citalopram significantly enhanced recognition memory, indicating an effect on memory consolidation. The fact that citalopram had an effect only when injected after S1 suggests that it may counteract its own consolidation-enhancing effect by interfering with memory acquisition. However, pretreatment with citalopram did not attenuate reboxetine's memory-enhancing effect. The D1/5-receptor antagonist SCH23390 blunted reboxetine's memory-enhancing effect, indicating a role of dopaminergic transmission in reboxetine-induced recognition memory enhancement. Our results suggest that antidepressant drugs specifically inhibiting noradrenaline reuptake enhance cognition and may be beneficial in the treatment of cognitive symptoms of depression. (c) 2015 APA, all rights reserved).

  15. Magnetic restricted-access microspheres for extraction of adrenaline, dopamine and noradrenaline from biological samples

    International Nuclear Information System (INIS)

    Xiao, Deli; Liu, Shubo; Liang, Liyun; Bi, Yanping

    2016-01-01

    Epoxy propyl bonded magnetic microspheres were prepared by atomic layer deposition using Fe 3 O 4 -SiO 2 microspheres as a core support material. Then, a restricted-access magnetic sorbent was prepared that contains diol groups on the external surface and m-aminophenylboronic acid groups on the internal surface. This kind of microspheres achieved excellent specific adsorption of the ortho-dihydroxy compounds (dopamine, adrenaline and noradrenaline). Following desorption with sorbitol, the ortho-dihydroxy compounds were quantified by HPLC. The limits of detection for dopamine, adrenaline and noradrenaline were 0.074, 0.053 and 0.095 μg mL −1 , respectively. Recoveries from spiked mice serum samples range from 80.2 to 89.1 %. (author)

  16. Protein kinase C and α 2-adrenoceptor-mediated inhibition of noradrenaline release from the rat tail artery

    International Nuclear Information System (INIS)

    Bucher, B.; Neuburger, J.; Illes, P.

    1991-01-01

    In isolated rat tail arteries preincubated with [3H]noradrenaline, electrical field stimulation evoked the overflow of tritium. Phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activating phorbol ester, time-dependently increased the overflow at 1 mumol/L but not at 0.1 mumol/L. In contrast, the overflow was not altered by phorbol 13-acetate (PA, 1 mumol/L), which does not influence the activity of PKC. Polymyxin B (70 mumol/L), an inhibitor of PKC, depressed the overflow when given alone and, in addition, attenuated the effect of PMA, 1 mumol/L. The selective alpha 2-adrenoceptor agonist B-HT 933 depressed the overflow; PMA, 1 mumol/L, did not interfere with the effect of B-HT 933, 10 mumol/L. The results provide evidence for the participation of prejunctionally located PKC in the release of noradrenaline. However, PKC does not seem to be involved in the alpha 2-adrenoceptor-agonist-mediated inhibition of noradrenaline release

  17. Tonic inhibition by orphanin FQ/nociceptin of noradrenaline neurotransmission in the amygdala

    NARCIS (Netherlands)

    Kawahara, Y; Hesselink, M.B.; van Scharrenburg, G; Westerink, B.H.C.

    2004-01-01

    The present microdialysis study investigated whether nociceptin/orphanin FQ exerts a tonic inhibition of the release of noradrenaline in the basolateral nucleus of the amygdala in awake rats. The non-peptide competitive nociceptin/orphanin FQ (N/OFQ) peptide receptor antagonist J-113397 (20 mg/kg

  18. Na+-independent, nifedipine-resistant rat afferent arteriolar Ca2+ responses to noradrenaline

    DEFF Research Database (Denmark)

    Salomonsson, Max; Braunstein, Thomas Hartig; von Holstein-Rathlou, Niels-Henrik

    2010-01-01

    Abstract Aim: In rat afferent arterioles we investigated the role of Na(+) entry in noradrenaline (NA)-induced depolarization and voltage-dependent Ca(2+) entry together with the importance of the transient receptor potential channel (TRPC) subfamily for non-voltage-dependent Ca(2+) entry. Methods...

  19. Noradrenaline, oxymetazoline and phorbol myristate acetate induce distinct functional actions and phosphorylation patterns of α1A-adrenergic receptors.

    Science.gov (United States)

    Alcántara-Hernández, Rocío; Hernández-Méndez, Aurelio; Romero-Ávila, M Teresa; Alfonzo-Méndez, Marco A; Pupo, André S; García-Sáinz, J Adolfo

    2017-12-01

    In LNCaP cells that stably express α 1A -adrenergic receptors, oxymetazoline increased intracellular calcium and receptor phosphorylation, however, this agonist was a weak partial agonist, as compared to noradrenaline, for calcium signaling. Interestingly, oxymetazoline-induced receptor internalization and desensitization displayed greater effects than those induced by noradrenaline. Phorbol myristate acetate induced modest receptor internalization and minimal desensitization. α 1A -Adrenergic receptor interaction with β-arrestins (colocalization/coimmunoprecipitation) was induced by noradrenaline and oxymetazoline and, to a lesser extent, by phorbol myristate acetate. Oxymetazoline was more potent and effective than noradrenaline in inducing ERK 1/2 phosphorylation. Mass spectrometric analysis of immunopurified α 1A -adrenergic receptors from cells treated with adrenergic agonists and the phorbol ester clearly showed that phosphorylated residues were present both at the third intracellular loop and at the carboxyl tail. Distinct phosphorylation patterns were observed under the different conditions. The phosphorylated residues were: a) Baseline and all treatments: T233; b) noradrenaline: S220, S227, S229, S246, S250, S389; c) oxymetazoline: S227, S246, S381, T384, S389; and d) phorbol myristate acetate: S246, S250, S258, S351, S352, S401, S402, S407, T411, S413, T451. Our novel data, describing the α 1A -AR phosphorylation sites, suggest that the observed different phosphorylation patterns may participate in defining adrenoceptor localization and action, under the different conditions examined. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. The modulatory effects of noradrenaline on vagal control of heart rate in the dogfish, Squalus acanthias.

    Science.gov (United States)

    Agnisola, Claudio; Randall, David J; Taylor, Edwin W

    2003-01-01

    The possible interactions between inhibitory vagal control of the heart and circulating levels of catecholamines in dogfish (Squalus acanthias) were studied using an in situ preparation of the heart, which retained intact its innervation from centrally cut vagus nerves. The response to peripheral vagal stimulation typically consisted of an initial cardiac arrest, followed by an escape beat, leading to renewed beating at a mean heart rate lower than the prestimulation rate (partial recovery). Cessation of vagal stimulation led to a transient increase in heart rate, above the prestimulation rate. This whole response was completely abolished by 10(-4) M atropine (a muscarinic cholinergic antagonist). The degree of vagal inhibition was evaluated in terms of both the initial, maximal cardiac interval and the mean heart rate during partial recovery, both expressed as a percentage of the prestimulation heart rate. The mean prestimulation heart rate of this preparation (36+/-4 beats min(-1)) was not affected by noradrenaline but was significantly reduced by 10(-4) M nadolol (a beta-adrenergic receptor antagonist), suggesting the existence of a resting adrenergic tone arising from endogenous catecholamines. The degree of vagal inhibition of heart rate varied with the rate of stimulation and was increased by the presence of 10(-8) M noradrenaline (the normal in vivo level in routinely active fish), while 10(-7) M noradrenaline (the in vivo level measured in disturbed or deeply hypoxic fish) reduced the cardiac response to vagal stimulation. In the presence of 10(-7) M noradrenaline, 10(-4) M nadolol further reduced the vagal response, while 10(-4) M nadolol + 10(-4) M phentolamine had no effect, indicating a complex interaction between adrenoreceptors, possibly involving presynaptic modulation of vagal inhibition.

  1. Stress at birth: plasma noradrenaline concentrations of women in labour and in cord blood.

    Science.gov (United States)

    Messow-Zahn, K; Sarafoff, M; Riegel, K P

    1978-03-15

    Radioenzymatically measured plasma noradrenaline concentrations, present at birth in umbilical veins of 19 healthy, 17 acutely asphyxiated, and 9 chronically distressed newborn infants were found to be elevated above maternal values proportional to the degree of distress and to plasma H ion concentrations.

  2. Noradrenaline concentration and turnover in nuclei of the hypothalamus and the medulla oblongata at two stages in the development of renal hypertension in the rat

    NARCIS (Netherlands)

    Wijnen, H.J.L.M.; Kloet, E.R. de; Versteeg, D.H.G.; Jong, Wybren de

    1980-01-01

    The noradrenaline concentration and the α-methyl-para-tyrosine (α-MPT)-induced disappearance of noradrenaline were determined in several nuclei of the hypothalamus and the medulla oblongata of renal hypertensive rats (two-kidney Goldblatt hypertension). A decreased α-MPT-induced disappearance of

  3. Functional adaptation of the human β-cells after frequent exposure to noradrenaline

    DEFF Research Database (Denmark)

    Dela, Flemming

    2015-01-01

    KEY POINTS: Trained people produce less insulin than untrained; there is an adaptation of the insulin-producing cells to the trained state. The mechanism behind this adaptation is not known, but some sort of memory must be introduced into the insulin-producing cells. Here it is shown that this me......KEY POINTS: Trained people produce less insulin than untrained; there is an adaptation of the insulin-producing cells to the trained state. The mechanism behind this adaptation is not known, but some sort of memory must be introduced into the insulin-producing cells. Here it is shown...... that this memory is introduced by 10 daily intravenous infusions of noradrenaline, mimicking the increases that occur during a 10 day training programme. Thus, after the infusion period, the subjects produced less insulin in response to the same stimulus. It is concluded that exercise-induced increases...... in noradrenaline is most likely the stimulus that introduces a memory in the insulin-producing cells. ABSTRACT: Physical training decreases glucose- and arginine-stimulated insulin secretion. The mechanism by which the pancreatic β-cells adapt to the training status of the individual is not known. We hypothesized...

  4. Lead-Induced Atypical Parkinsonism in Rats: Behavioral, Electrophysiological, and Neurochemical Evidence for a Role of Noradrenaline Depletion

    Directory of Open Access Journals (Sweden)

    Mariam Sabbar

    2018-03-01

    Full Text Available Background: Lead neurotoxicity is a major health problem known as a risk factor for neurodegenerative diseases, including the manifestation of parkinsonism-like disorder. While lead is known to preferentially accumulate in basal ganglia, the mechanisms underlying behavioral disorders remain unknown. Here, we investigated the neurophysiological and biochemical correlates of motor deficits induced by sub-chronic injections of lead.Methods: Sprague Dawely rats were exposed to sub-chronic injections of lead (10 mg/kg, i.p. or to a single i.p. injection of 50 mg/kg N-(2-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4, a drug known to induce selective depletion of noradrenaline. Rats were submitted to a battery of behavioral tests, including the open field for locomotor activity and rotarod for motor coordination. Electrophysiological recordings were carried out in three major basal ganglia nuclei, the subthalamic nucleus (STN, globus pallidus (GP, and substantia nigra pars reticulata (SNr. At the end of experiments, post-mortem tissue level of the three monoamines (dopamine, noradrenaline, and serotonin and their metabolites has been determined using HPLC.Results: Lead intoxication significantly impaired exploratory and locomotor activity as well as motor coordination. It resulted in a significant reduction in the level of noradrenaline in the cortex and dopamine and its metabolites, DOPAC, and HVA, in the striatum. The tissue level of serotonin and its metabolite 5-HIAA was not affected in the two structures. Similarly, DSP-4, which induced a selective depletion of noradrenaline, significantly decreased exploratory, and locomotor activity as well as motor coordination. L-DOPA treatment did not improve motor deficits induced by lead and DSP-4 in the two animal groups. Electrophysiological recordings showed that both lead and DSP-4 did not change the firing rate but resulted in a switch from the regular normal firing to irregular and

  5. [Presence of conjugated noradrenaline in the walls of the nest of Vespula germanica Linné].

    Science.gov (United States)

    Lecomte, J; Bourdon, V; Damas, J; Leclercq, M; Leclercq, J

    1976-01-01

    Conjugated noradrenaline (NA) has been identified as a constituant of the walls of a Vespid wasp: Vespula germanica Linne. Concentrations range between 1,8 mug/g (external wall) and 18 mug/g (internal structure). Probably NA originates from the saliva of the Hymenoptera.

  6. CO-RELEASED ADRENALINE MARKEDLY FACILITATES NORADRENALINE OVERFLOW THROUGH PREJUNCTIONAL BETA(2)-ADRENOCEPTORS DURING SWIMMING EXERCISE

    NARCIS (Netherlands)

    COPPES, RP; SMIT, J; BENTHEM, L; VANDERLEEST, J; ZAAGSMA, J

    1995-01-01

    The effect of intravenously applied (-)adrenaline, taken up by and released from sympathetic nerves, on swimming exercise-induced noradrenaline overflow in permanently cannulated adrenal demedullated rats was studied. Adrenaline (100 ng/min) was infused for 2 h, during which a plasma concentration

  7. Cutaneous noradrenaline measured by microdialysis in complex regional pain syndrome during whole-body cooling and heating

    DEFF Research Database (Denmark)

    Terkelsen, Astrid Juhl; Gierthmühlen, Janne; Petersen, Lars J.

    2013-01-01

    and in healthy volunteers. Seven patients and nine controls completed whole-body cooling (sympathetic activation) and heating (sympathetic inhibition) induced by a whole-body thermal suit with simultaneous measurement of the skin temperature, skin blood flow, and release of dermal noradrenaline. CRPS pain...

  8. Olfactory Perceptual Learning Requires Action of Noradrenaline in the Olfactory Bulb: Comparison with Olfactory Associative Learning

    Science.gov (United States)

    Vinera, Jennifer; Kermen, Florence; Sacquet, Joëlle; Didier, Anne; Mandairon, Nathalie; Richard, Marion

    2015-01-01

    Noradrenaline contributes to olfactory-guided behaviors but its role in olfactory learning during adulthood is poorly documented. We investigated its implication in olfactory associative and perceptual learning using local infusion of mixed a1-ß adrenergic receptor antagonist (labetalol) in the adult mouse olfactory bulb. We reported that…

  9. Hypofunction of prefrontal cortex NMDA receptors does not change stress-induced release of dopamine and noradrenaline in amygdala but disrupts aversive memory.

    Science.gov (United States)

    Del Arco, Alberto; Ronzoni, Giacomo; Mora, Francisco

    2015-07-01

    A dysfunction of prefrontal cortex has been associated with the exacerbated response to stress observed in schizophrenic patients and high-risk individuals to develop psychosis. The hypofunction of NMDA glutamatergic receptors induced by NMDA antagonists produces cortico-limbic hyperactivity, and this is used as an experimental model to resemble behavioural abnormalities observed in schizophrenia. The aim of the present study was to investigate whether injections of NMDA antagonists into the medial prefrontal cortex of the rat change (1) the increases of dopamine, noradrenaline and corticosterone concentrations produced by acute stress in amygdala, and (2) the acquisition of aversive memory related to a stressful event. Male Wistar rats were implanted with guide cannulae to perform microdialysis and bilateral microinjections (0.5 μl/side) of the NMDA antagonist 3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phophonic acid (CPP) (25 and 100 ng). Prefrontal injections were performed 60 min before restraint stress in microdialysis experiments, or training (footshock; 0.6 mA, 2 s) in inhibitory avoidance test. Retention latency was evaluated 24 h after training as an index of aversive memory. Acute stress increased amygdala dialysate concentrations of dopamine (160% of baseline), noradrenaline (145% of baseline) and corticosterone (170% of baseline). Prefrontal injections of CPP did not change the increases of dopamine, noradrenaline or corticosterone produced by stress. In contrast, CPP significantly reduced the retention latency in the inhibitory avoidance test. These results suggest that the hypofunction of prefrontal NMDA receptors does not change the sensitivity to acute stress of dopamine and noradrenaline projections to amygdala but impairs the acquisition of aversive memory.

  10. Noradrenaline and Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Claire eDelaville

    2011-05-01

    Full Text Available Parkinson’s disease (PD is characterized by the degeneration of dopamine (DA neurons in the substantia nigra pars compacta, and motor symptoms including bradykinesia, rigidity and tremor at rest. These symptoms are manifest when around 70% of striatal DA is lost. In addition to motor deficits, PD is also characterized by the manifestation of non-motor symptoms. However, depletion of DA alone in animal models has failed to simultaneously elicit both the motor and non-motor deficits of PD because the disease is a multi-system disorder that features a profound loss of other neurotransmitter systems. There is growing evidence that additional loss of noradrenaline (NA neurons of the locus coeruleus, the principal source of NA in the brain, could be involved in the clinical expression of motor as well as in non-motor deficits. In the present review, we analyzed the latest data obtained from animal models of parkinsonism and from parkinsonian patients providing evidence for the implication of NA in the pathophysiology of PD. Recent studies have shown that NA depletion alone or combined with DA depletion resulted in motor as well as in non-motor dysfunctions. In addition, by using selective agonists and antagonists of alpha receptors we, and others, have shown that α2 receptors are implicated in the control of motor activity and that α2 receptor antagonists can improve PD motor symptoms as well as L-Dopa-induced dyskinesia. Here we provide arguments that the loss of NA neurons in PD has an impact on all PD symptoms and that the association of NAergic agents to dopaminergic medication can be beneficial in the treatment of the disease.

  11. Noradrenaline spillover during exercise in active versus resting skeletal muscle in man

    DEFF Research Database (Denmark)

    Savard, G; Strange, S; Kiens, Bente

    1987-01-01

    Increases in plasma noradrenaline (NA) concentration occur during moderate to heavy exercise in man. This study was undertaken to examine the spillover of NA from both resting and contracting skeletal muscle during exercise. Six male subjects performed one-legged knee-extension so that all...... in the exercising leg than in the resting leg both during 50% and 100% leg exercise. These results suggest that contracting skeletal muscle may contribute to a larger extent than resting skeletal muscle to increasing the level of plasma NA during exercise. Contractile activity may influence the NA spillover from...

  12. Investigation of the mechanisms underlying the hypophagic effects of the 5-HT and noradrenaline reuptake inhibitor, sibutramine, in the rat

    Science.gov (United States)

    Jackson, Helen C; Bearham, M Clair; Hutchins, Lisa J; Mazurkiewicz, Sarah E; Needham, Andrew M; Heal, David J

    1997-01-01

    Sibutramine is a novel 5-hydroxytryptamine (5-HT) and noradrenaline reuptake inhibitor (serotonin- noradrenaline reuptake inhibitor, SNRI) which is currently being developed as a treatment for obesity. Sibutramine has been shown to decrease food intake in the rat. In this study we have used a variety of monoamine receptor antagonists to examine the pharmacological mechanisms underlying sibutramine-induced hypophagia. Individually-housed male Sprague-Dawley rats were maintained on reversed phase lighting with free access to food and water. Drugs were administered at 09 h 00 min and food intake was monitored over the following 8 h dark period. Sibutramine (10 mg kg−1, p.o.) produced a significant decrease in food intake during the 8 h following drug administration. This hypophagic response was fully antagonized by the α1-adrenoceptor antagonist, prazosin (0.3 and 1 mg kg−1, i.p.), and partially antagonized by the β1-adrenoceptor antagonist, metoprolol (3 and 10 mg kg−1, i.p.) and the 5-HT receptor antagonists, metergoline (non-selective; 0.3 mg kg−1, i.p.); ritanserin (5-HT2A/2C; 0.1 and 0.5 mg kg−1, i.p.) and SB200646 (5-HT2B/2C; 20 and 40 mg kg−1, p.o.). By contrast, the α2-adrenoceptor antagonist, RX821002 (0.3 and 1 mg kg−1, i.p.) and the β2-adrenoceptor antagonist, ICI 118,551 (3 and 10 mg kg−1, i.p.) did not reduce the decrease in food intake induced by sibutramine. These results demonstrate that β1-adrenoceptors, 5-HT2A/2C-receptors and particularly α1-adrenoceptors, are involved in the effects of sibutramine on food intake and are consistent with the hypothesis that sibutramine-induced hypophagia is related to its ability to inhibit the reuptake of both noradrenaline and 5-HT, with the subsequent activation of a variety of noradrenaline and 5-HT receptor systems. PMID:9283694

  13. Noradrenaline might enhance assertive human social behaviours: an investigation in a flatmate relationship.

    Science.gov (United States)

    Tse, W S; Bond, A J

    2006-09-01

    The aim of the present study was to explore the role of noradrenaline on the social behaviour of healthy volunteers when they were interacting with a familiar person, their flatmate. Interaction with the flatmate was explored in a cooperative game situation. Ten pairs of same-sex healthy volunteer flatmates aged 18-25 years were recruited for the experiment. All volunteers gave written informed consent and the study was approved by the institutional ethical committee. A randomised, double blind, placebo-controlled crossover trial of reboxetine versus placebo was conducted. In each of the 10 pairs of volunteers, one (subject) volunteered to take the tablets and the other (flatmate) received no treatment. Reboxetine (4 mg/bd) and placebo were administered orally as identical capsules for 2 weeks. The subjects were randomly assigned to receive either reboxetine or placebo first and there was a two-week washout period following the first treatment. At baseline and the end of each treatment, they filled in the Beck Depression Inventory (BDI), Social Adapation Self-Evaluation Scale (SASS), and Aggression Questionnaire (AQ). Then, they were instructed to play the Tangrams game. This task elicits face-valid social behaviours such as cooperation, giving commands and unilateral grasps. Analysis of covariance showed that there was a statistical trend for reboxetine treatment to increase commands (p=0.055). This study presents preliminary evidence that two weeks' enhancement of noradrenaline transmission induced by reboxetine makes healthy volunteers more self-confident and assertive.

  14. Determination of adrenaline, noradrenaline and corticosterone in rodent blood by ion pair reversed phase UHPLC-MS/MS.

    Science.gov (United States)

    Bergh, Marianne Skov-Skov; Bogen, Inger Lise; Andersen, Jannike Mørch; Øiestad, Åse Marit Leere; Berg, Thomas

    2018-01-01

    A novel ion pair reversed phase ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous determination of the stress hormones adrenaline, noradrenaline and corticosterone in rodent blood was developed and fully validated. Separations were performed on an Acquity HSS T3 column (2.1mm i.d.×100mm, 1.8μm) with gradient elution and a runtime of 5.5min. The retention of adrenaline and noradrenaline was substantially increased by employing the ion pair reagent heptafluorobutyric acid (HFBA). Ion pair reagents are usually added to the mobile phase only, but we demonstrate for the first time that including HFBA to the sample reconstitution solvent as well, has a major impact on the chromatography of these compounds. The stability of adrenaline and corticosterone in rodent blood was investigated using the surrogate analytes adrenaline-d 3 and corticosterone-d 8 . The applicability of the described method was demonstrated by measuring the concentration of stress hormones in rodent blood samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Reduced capacity of cardiac efferent sympathetic neurons to release noradrenaline and modify cardiac function in tachycardia-induced canine heart failure.

    Science.gov (United States)

    Cardinal, R; Nadeau, R; Laurent, C; Boudreau, G; Armour, J A

    1996-09-01

    To investigate the capacity of efferent sympathetic neurons to modulate the failing heart, stellate ganglion stimulation was performed in dogs with biventricular heart failure induced by rapid ventricular pacing (240 beats/min) for 4-6 weeks. Less noradrenaline was released from cardiac myoneural junctions into coronary sinus blood in response to left stellate ganglion stimulation in anesthetized failing heart preparations (582 pg/mL, lower and upper 95% confidence intervals of 288 and 1174 pg/mL, n = 19) compared with healthy heart preparations (6391 pg/mL, 95% confidence intervals of 4180 and 9770 pg/mL, n = 14; p < 0.001). There was substantial adrenaline extraction by failing hearts (49 +/- 6%), although it was slightly lower than in healthy heart preparations (65 +/- 9%, p = 0.055). In contrast with healthy heart preparations, no net release of adrenaline occurred during stellate ganglion stimulation in any of the failing heart preparations, and ventricular tissue levels of adrenaline fell below the sensitivity limit of the HPLC technique. In failing heart preparations, maximal electrical stimulation of right or left stellate ganglia resulted in minimal augmentation of left ventricular intramyocardial (17%) and chamber (12%) systolic pressures. These indices were augmented by 145 and 97%, respectively, following exogenous noradrenaline administration. Thus, the cardiac efferent sympathetic neurons' reduced capacity to release noradrenaline and modify cardiac function can contribute to reduction of sympathetic support to the failing heart.

  16. Noradrenaline and dopamine levels in acute cerveau isolé in the cat.

    Science.gov (United States)

    Szikszay, M; Benedek, G; Obál, F; Obál, F

    1980-01-01

    Noradrenaline (NA) and dopamine (DA) levels were studied in the forebrain of acute immobilized cats and in cerveau isolé preparations. A gradual decrease in NA and DA was observed one and two hours after high mesencephalic transection, while the amount of NA increased in acute immobilized cats after the cessation of ether anaesthesia. These changes in NA level are consistent with the observations suggesting an inverse relationship between NA and cortical deactivation. The decrease of DA with an exaggeration of spindle activity and increased synchronizing effect of basal forebrain stimulation indicate that the spindle-increasing effect of DA suggested by several authors requires the contribution of the brain stem.

  17. Blockade of the high-affinity noradrenaline transporter (NET) by the selective 5-HT reuptake inhibitor escitalopram: an in vivo microdialysis study in mice

    Science.gov (United States)

    Nguyen, Hai T; Guiard, Bruno P; Bacq, Alexandre; David, Denis J; David, Indira; Quesseveur, Gaël; Gautron, Sophie; Sanchez, Connie; Gardier, Alain M

    2013-01-01

    BACKGROUND AND PURPOSE Escitalopram, the S(+)-enantiomer of citalopram is the most selective 5-HT reuptake inhibitor approved. Although all 5-HT selective reuptake inhibitors (SSRIs) increase extracellular levels of 5-HT ([5-HT]ext). some also enhance, to a lesser extent, extracellular levels of noradrenaline ([NA]ext). However, the mechanisms by which SSRIs activate noradrenergic transmission in the brain remain to be determined. EXPERIMENTAL APPROACH This study examined the effects of escitalopram, on both [5-HT]ext and [NA]ext in the frontal cortex (FCx) of freely moving wild-type (WT) and mutant mice lacking the 5-HT transporter (SERT−/−) by using intracerebral microdialysis. We explored the possibilities that escitalopram enhances [NA]ext, either by a direct mechanism involving the inhibition of the low- or high-affinity noradrenaline transporters, or by an indirect mechanism promoted by [5-HT]ext elevation. The forced swim test (FST) was used to investigate whether enhancing cortical [5-HT]ext and/or [NA]ext affected the antidepressant-like activity of escitalopram. KEY RESULTS In WT mice, a single systemic administration of escitalopram produced a significant increase in cortical [5-HT]ext and [NA]ext. As expected, escitalopram failed to increase cortical [5-HT]ext in SERT−/− mice, whereas its neurochemical effects on [NA]ext persisted in these mutants. In WT mice subjected to the FST, escitalopram increased swimming parameters without affecting climbing behaviour. Finally, escitalopram, at relevant concentrations, failed to inhibit cortical noradrenaline and 5-HT uptake mediated by low-affinity monoamine transporters. CONCLUSIONS AND IMPLICATIONS These experiments suggest that escitalopram enhances, although moderately, cortical [NA]extin vivo by a direct mechanism involving the inhibition of the high-affinity noradrenaline transporter (NET). PMID:22233336

  18. The wake-promoting hypocretin/orexin neurons change their response to noradrenaline after sleep deprivation.

    Science.gov (United States)

    Grivel, Jeremy; Cvetkovic, Vesna; Bayer, Laurence; Machard, Danièle; Tobler, Irene; Mühlethaler, Michel; Serafin, Mauro

    2005-04-20

    Sleep deprivation is accompanied by the progressive development of an irresistible need to sleep, a phenomenon whose mechanism has remained elusive. Here, we identified for the first time a reflection of that phenomenon in vitro by showing that, after a short 2 h period of total sleep deprivation, the action of noradrenaline on the wake-promoting hypocretin/orexin neurons changes from an excitation to an inhibition. We propose that such a conspicuous modification of responsiveness should contribute to the growing sleepiness that accompanies sleep deprivation.

  19. Neonatal 6-hydroxydopamine treatment: Noradrenaline levels and in vitro 3H-catecholamine synthesis in discrete brain regions of adult rats

    NARCIS (Netherlands)

    Versteeg, D.H.G.; Ree, J.M. van; Provoost, Abraham P.; Jong, Wybren de

    1974-01-01

    Endogenous noradrenaline levels are elevated in medulla oblongata, mesencephalon, pons and thalamus of adult rats which had been treated with 6-hydroxydopamine on days 1, 2, 8 and 15 after birth. Levels in spinal cord, cerebellum, hippocampus/amygdala and cortex are depressed, whereas no significant

  20. CFTR mediates noradrenaline-induced ATP efflux from DRG neurons.

    Science.gov (United States)

    Kanno, Takeshi; Nishizaki, Tomoyuki

    2011-09-24

    In our earlier study, noradrenaline (NA) stimulated ATP release from dorsal root ganglion (DRG) neurons as mediated via β(3) adrenoceptors linked to G(s) protein involving protein kinase A (PKA) activation, to cause allodynia. The present study was conducted to understand how ATP is released from DRG neurons. In an outside-out patch-clamp configuration from acutely dissociated rat DRG neurons, single-channel currents, sensitive to the P2X receptor inhibitor PPADS, were evoked by approaching the patch-electrode tip close to a neuron, indicating that ATP is released from DRG neurons, to activate P2X receptor. NA increased the frequency of the single-channel events, but such NA effect was not found for DRG neurons transfected with the siRNA to silence the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In the immunocytochemical study using acutely dissociated rat DRG cells, CFTR was expressed in neurons alone, but not satellite cells, fibroblasts, or Schwann cells. It is concluded from these results that CFTR mediates NA-induced ATP efflux from DRG neurons as an ATP channel.

  1. Selective noradrenaline depletion impairs working memory and hippocampal neurogenesis.

    Science.gov (United States)

    Coradazzi, Marino; Gulino, Rosario; Fieramosca, Francesco; Falzacappa, Lucia Verga; Riggi, Margherita; Leanza, Giampiero

    2016-12-01

    Noradrenergic neurons in the locus coeruleus play a role in learning and memory, and their loss is an early event in Alzheimer's disease pathogenesis. Moreover, noradrenaline may sustain hippocampal neurogenesis; however, whether are these events related is still unknown. Four to five weeks following the selective immunotoxic ablation of locus coeruleus neurons, young adult rats underwent reference and working memory tests, followed by postmortem quantitative morphological analyses to assess the extent of the lesion, as well as the effects on proliferation and/or survival of neural progenitors in the hippocampus. When tested in the Water Maze task, lesioned animals exhibited no reference memory deficit, whereas working memory abilities were seen significantly impaired, as compared with intact or sham-lesioned controls. Stereological analyses confirmed a dramatic noradrenergic neuron loss associated to reduced proliferation, but not survival or differentiation, of 5-bromo-2'deoxyuridine-positive progenitors in the dentate gyrus. Thus, ascending noradrenergic afferents may be involved in more complex aspects of cognitive performance (i.e., working memory) possibly via newly generated progenitors in the hippocampus. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Surplus dietary tryptophan reduces plasma cortisol and noradrenaline concentrations and enhances recovery after social stress in pigs.

    Science.gov (United States)

    Koopmans, Sietse Jan; Ruis, Marko; Dekker, Ruud; van Diepen, Hans; Korte, Mechiel; Mroz, Zdzislaw

    2005-07-21

    Social stress occurs in intensive pig farming due to aggressive behavior. This stress may be reduced at elevated dietary levels of tryptophan (TRP). In this study, we compared the effects of high (13.2%) vs. normal (3.4%) dietary TRP to large neutral amino acid (LNAA) ratios on behavior and stress hormones in catheterized pigs ( approximately 50 kg BW), which were exposed to social stress by placing them twice into the territory of a dominant pig ( approximately 60 kg) for 15 min. Pre-stress plasma TRP concentrations were 156+/-15 vs. 53+/-6 micromol/l (psocial confrontations, pigs on the high vs. normal TRP diets show a tendency towards reduced active avoidance behavior (3.2+/-1.1 vs. 6.7+/-1.2 min, psocial confrontations, the post-stress plasma cortisol, noradrenaline and adrenaline concentrations and/or curves (from +5 min to 2 h) were lower/steeper (psurplus TRP in diets for pigs (1) does not significantly affect behavior when exposed to social stress, (2) reduces basal plasma cortisol and noradrenaline concentrations, (3) does not affect the immediate hormonal response to stress, and (4) reduces the long-term hormonal response to stress. In general, pigs receiving high dietary TRP were found to be less affected by stress.

  3. GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior

    Directory of Open Access Journals (Sweden)

    Fuka Aizawa

    2016-12-01

    Full Text Available The free fatty acid receptor 1 (GPR40/FFAR1 is a G protein-coupled receptor, which is activated by long chain fatty acids. We have previously demonstrated that activation of brain GPR40/FFAR1 exerts an antinociceptive effect that is mediated by the modulation of the descending pain control system. However, it is unclear whether brain GPR40/FFAR1 contributes to emotional function. In this study, we investigated the involvement of GPR40/FFAR1 in emotional behavior using GPR40/FFAR1 deficient (knockout, KO mice. The emotional behavior in wild and KO male mice was evaluated at 9–10 weeks of age by the elevated plus-maze test, open field test, social interaction test, and sucrose preference test. Brain monoamines levels were measured using LC–MS/MS. The elevated plus-maze test and open field tests revealed that the KO mice reduced anxiety-like behavior. There were no differences in locomotor activity or social behavior between the wild and KO mice. In the sucrose preference test, the KO mice showed reduction in sucrose preference and intake. The level of noradrenaline was higher in the hippocampus, medulla oblongata, hypothalamus and midbrain of KO mice. Therefore, these results suggest that brain GPR40/FFAR1 is associated with anxiety- and depression-related behavior regulated by the increment of noradrenaline in the brain.

  4. Noradrenaline and adrenaline concentrations in various vascular beds in patients with cirrhosis. Relation to haemodynamics

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Christensen, N J; Ring-Larsen, H

    1981-01-01

    indicates that sympathetic nervous activity is enhanced in patients with cirrhosis. Based on the above positive correlation between NA and heart rate and the significant release of NA from the kidney, it may be hypothesized that the increased sympathetic nervous activity especially involves heart and kidney......Plasma noradrenaline (NA) and adrenaline (A) concentrations were related to various haemodynamic parameters in fifteen patients with cirrhosis. In supine position at rest plasma NA and A in peripheral venous blood were significantly higher in patients with cirrhosis than in normal subjects. Mean...

  5. The postirradiation effect of noradrenaline, serotonin and dopamine on Na-K-pump activity in rat brain sections

    International Nuclear Information System (INIS)

    Dvoretskij, A.I.; Kulikova, I.A.

    1993-01-01

    Whole-body X-irradiation with doses of 0.155 and 0.310 C/kg was shown to modify in different ways the activating effects of noradrenaline and serotonin, as well as a biphase effect of dopamine of neuronal membranes. The resulting effect was a function of a combination of radiation doses and neurotransmitter concentrations and thus showed different modes of interaction between neurotransmitter and ion-transport systems of brain cells in radiation sickness

  6. Interrupting prolonged sitting with brief bouts of light walking or simple resistance activities reduces resting blood pressure and plasma noradrenaline in type 2 diabetes.

    Science.gov (United States)

    Dempsey, Paddy C; Sacre, Julian W; Larsen, Robyn N; Straznicky, Nora E; Sethi, Parneet; Cohen, Neale D; Cerin, Ester; Lambert, Gavin W; Owen, Neville; Kingwell, Bronwyn A; Dunstan, David W

    2016-12-01

    Prolonged sitting is increasingly recognized as a ubiquitous cardiometabolic risk factor, possibly distinct from lack of physical exercise. We examined whether interrupting prolonged sitting with brief bouts of light-intensity activity reduced blood pressure (BP) and plasma noradrenaline in type 2 diabetes (T2D). In a randomized crossover trial, 24 inactive overweight/obese adults with T2D (14 men; mean ± SD; 62 ± 6 years) consumed standardized meals during 3 × 8 h conditions: uninterrupted sitting (SIT); sitting + half-hourly bouts of walking (3.2 km/h for 3-min) (light-intensity walking); and sitting + half-hourly bouts of simple resistance activities for 3 min (SRAs), each separated by 6-14 days washout. Resting seated BP was measured hourly (mean of three recordings, ≥20-min postactivity). Plasma noradrenaline was measured at 30-min intervals for the first hour after meals and hourly thereafter. Compared with SIT, mean resting SBP and DBP were significantly reduced (P light-intensity walking (mean ± SEM; -14 ± 1/-8 ± 1 mmHg) and SRA (-16 ± 1/-10 ± 1 mmHg), with a more pronounced effect for SRA (P light-intensity walking). Similarly, mean plasma noradrenaline was significantly reduced for both light-intensity walking (-0.3 ± 0.1 nmol/l) and SRA (-0.6 ± 0.1 nmol/l) versus SIT, with SRA lower than light-intensity walking (P light-intensity walking (-3 ± 1 bpm; P light-intensity walking or SRA reduces resting BP and plasma noradrenaline in adults with T2D, with SRA being more effective. Given the ubiquity of sedentary behaviors and poor adherence to structured exercise, this approach may have important implications for BP management in patients with T2D.

  7. Ca2+ influx insensitive to organic Ca2+ entry blockers contributes to noradrenaline-induced contractions of the isolated guinea pig aorta

    NARCIS (Netherlands)

    Gouw, M. A.; Wilffert, B.; Wermelskirchen, D.; van Zwieten, P. A.

    1990-01-01

    We determined the contribution of intracellular Ca2+ to the noradrenaline (NA, 3 X 10(-5) mmol/l)-induced contraction of the isolated guinea pig aorta. Since only about 55% of the NA-induced contraction could be attributed to intracellular Ca2+ release, we assumed that a Ca2+ influx component

  8. Pressor Response to Noradrenaline in the Setting of Septic Shock: Anything New under the Sun—Dexmedetomidine, Clonidine? A Minireview

    Directory of Open Access Journals (Sweden)

    A. Géloën

    2015-01-01

    Full Text Available Progress over the last 50 years has led to a decline in mortality from ≈70% to ≈20% in the best series of patients with septic shock. Nevertheless, refractory septic shock still carries a mortality close to 100%. In the best series, the mortality appears related to multiple organ failure linked to comorbidities and/or an intense inflammatory response: shortening the period that the subject is exposed to circulatory instability may further lower mortality. Treatment aims at reestablishing circulation within a “central” compartment (i.e., brain, heart, and lung but fails to reestablish a disorganized microcirculation or an adequate response to noradrenaline, the most widely used vasopressor. Indeed, steroids, nitric oxide synthase inhibitors, or donors have not achieved overwhelming acceptance in the setting of septic shock. Counterintuitively, α2-adrenoceptor agonists were shown to reduce noradrenaline requirements in two cases of human septic shock. This has been replicated in rat and sheep models of sepsis. In addition, some data show that α2-adrenoceptor agonists lead to an improvement in the microcirculation. Evidence-based documentation of the effects of alpha-2 agonists is needed in the setting of human septic shock.

  9. GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior.

    Science.gov (United States)

    Aizawa, Fuka; Nishinaka, Takashi; Yamashita, Takuya; Nakamoto, Kazuo; Kurihara, Takashi; Hirasawa, Akira; Kasuya, Fumiyo; Miyata, Atsuro; Tokuyama, Shogo

    2016-12-01

    The free fatty acid receptor 1 (GPR40/FFAR1) is a G protein-coupled receptor, which is activated by long chain fatty acids. We have previously demonstrated that activation of brain GPR40/FFAR1 exerts an antinociceptive effect that is mediated by the modulation of the descending pain control system. However, it is unclear whether brain GPR40/FFAR1 contributes to emotional function. In this study, we investigated the involvement of GPR40/FFAR1 in emotional behavior using GPR40/FFAR1 deficient (knockout, KO) mice. The emotional behavior in wild and KO male mice was evaluated at 9-10 weeks of age by the elevated plus-maze test, open field test, social interaction test, and sucrose preference test. Brain monoamines levels were measured using LC-MS/MS. The elevated plus-maze test and open field tests revealed that the KO mice reduced anxiety-like behavior. There were no differences in locomotor activity or social behavior between the wild and KO mice. In the sucrose preference test, the KO mice showed reduction in sucrose preference and intake. The level of noradrenaline was higher in the hippocampus, medulla oblongata, hypothalamus and midbrain of KO mice. Therefore, these results suggest that brain GPR40/FFAR1 is associated with anxiety- and depression-related behavior regulated by the increment of noradrenaline in the brain. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  10. Ca2+influx insensitive to organic Ca2+entry blockers contributes to noradrenaline-induced contractions of the isolated guinea pig aorta

    NARCIS (Netherlands)

    Gouw, M.A.M.; Wilffert, B.; Wermelskirchen, D.; Van Zwieten, P.A.

    1990-01-01

    We determined the contribution of intracellular Ca2+to the noradrenaline (NA, 3 x 10-5mmol/l)-induced contraction of the isolated guinea pig aorta. Since only about 55% of the NA-induced contraction could be attributed to intracellular Ca2+release, we assumed that a Ca2+influx component contributes

  11. Plasma cortisol and noradrenalin concentrations in pigs: automated sampling of freely moving pigs housed in PigTurn versus manually sampled and restrained pigs

    Science.gov (United States)

    Minimizing the effects of restraint and human interaction on the endocrine physiology of animals is essential for collection of accurate physiological measurements. Our objective was to compare stress-induced cortisol (CORT) and noradrenalin (NorA) responses in automated versus manual blood sampling...

  12. M-octopamine injected into the paraventricular nucleus induces eating in rats: a comparison with noradrenaline-induced eating.

    OpenAIRE

    Fletcher, P. J.; Paterson, I. A.

    1989-01-01

    1. The effects on food intake in rats of injection of m- and p-octopamine into the paraventricular nucleus (PVN) of the hypothalamus were examined, and compared to the effects of noradrenaline (NA). 2. m-Octopamine injected into the PVN induced a dose-dependent increase in food intake, with the maximal effect occurring at a dose of 25 nmol. p-Octopamine did not elicit eating unless it was administered to animals pretreated with the monoamine oxidase inhibitor, pargyline. 3. The effects of pre...

  13. 5-HT has contrasting effects in the frontal cortex, but not the hypothalamus, on changes in noradrenaline efflux induced by the monoamine releasing-agent, d-amphetamine, and the reuptake inhibitor, BTS 54 354.

    Science.gov (United States)

    Géranton, Sandrine M; Heal, David J; Stanford, S Clare

    2004-03-01

    There is extensive evidence for functional interactions between central noradrenergic and serotonergic neurones. Here, dual-probe microdialysis was used in freely-moving rats to compare the effects of 5-HT on noradrenergic transmission in the rat frontal cortex and hypothalamus. We studied the effects of the 5-HT synthesis inhibitor, para-chlorophenylalanine (pCPA; which depleted 5-HT stores in both the frontal cortex and the hypothalamus), on spontaneous efflux of noradrenaline and on the noradrenergic responses to d-amphetamine, and the monoamine reuptake inhibitor, BTS 54 354. pCPA pretreatment alone did not affect spontaneous noradrenaline efflux in either brain region, whether or not alpha2-autoreceptors were inactivated by administration of the alpha2-antagonist, atipamezole (1 mg/kg i.p). However, in the frontal cortex, pCPA pretreatment augmented the amplitude of, and prolonged, the noradrenergic response to local infusion of d-amphetamine (10 microM). In contrast, pCPA abolished the increase in cortical noradrenaline efflux induced by local infusion of BTS 54 354 (50 microM). In the hypothalamus, pCPA did not affect the amplitude of the response to either of these agents but did prolong the effects of d-amphetamine on noradrenaline efflux. These findings suggest that serotonergic transmission has complex effects on the noradrenergic response to drugs that increase noradrenergic transmission in the frontal cortex, but has less influence in the hypothalamus.

  14. Accumulation of radioactivity after repeated infusion of 3H-adrenaline and 3H-noradrenaline in the rat as a model animal.

    Science.gov (United States)

    Lepschy, M; Filip, T; Palme, R G

    2014-10-01

    Besides enzymatic inactivation, catecholamines bind non-enzymatically and irreversible to proteins. The physiological impact of these catecholamine adducts is still unclear. We therefore collected basic data about the distribution of catecholamine adducts in the rat after repeated intravenous administration of (3)H-adrenaline and (3)H-noradrenaline. In all animals radioactivity in blood increased until the last injection on Day 7 and decreased then slowly close to background values (plasma) or remained higher (erythrocytes). In all sampled tissues radioactivity could be found, but only in hair high amounts remained present even after 3 weeks. Half-life of rat serum albumin loaded with (3)H-adrenaline or (3)H-noradrenaline was not altered. This study provides basic knowledge about the distribution of catecholamines or their adducts, but physiological effects could not be demonstrated. However, for the first time deposition and accumulation of catecholamines (adducts) in the hair could be proven, suggesting that hair might be used for evaluating long term stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Role of glycogenolysis in memory and learning: regulation by noradrenaline, serotonin and ATP

    Directory of Open Access Journals (Sweden)

    Marie Elizabeth Gibbs

    2016-01-01

    Full Text Available This paper reviews the role played by glycogen breakdown (glycogenolysis and glycogen re-synthesis in memory processing in two different chick brain regions, (1 the hippocampus and (2 the avian equivalent of the mammalian cortex, the intermediate medial mesopallium (IMM. Memory processing is regulated by the neuromodulators noradrenaline and serotonin soon after training and glycogen breakdown and re-synthesis are involved. In day-old domestic chicks, memory formation is dependent on the breakdown of glycogen (glycogenolysis at three specific times during the first 60 min after learning (around 2.5, 30 and 55 min. The chicks learn to discriminate in a single trial between beads of two colours and tastes. Inhibition of glycogen breakdown by the inhibitor of glycogen phosphorylase 1,4-dideoxy-1,4-imino-D-arabinitol (DAB given at specific times prior to the formation of long-term memory prevents memory forming. Noradrenergic stimulation of cultured chicken astrocytes by a selective β2-adrenergic (AR agonist reduces glycogen levels and we believe that in vivo this triggers memory consolidation at the second stage of glycogenolysis. Serotonin acting at 5-HT2B receptors acts on the first stage, but not on the second. We have shown that noradrenaline, acting via post-synaptic α2-ARs, is also responsible for the synthesis of glycogen and our experiments suggest that there is a readily accessible labile pool of glycogen in astrocytes which is depleted within 10 min if glycogen synthesis is inhibited. Endogenous ATP promotion of memory consolidation at 2.5 and 30 min is also dependent on glycogen breakdown. ATP acts at P2Y1 receptors and the action of thrombin suggests that it causes the release of internal calcium ([Ca2+]i] in astrocytes. Glutamate and GABA, the primary neurotransmitters in the brain, cannot be synthesized in neurons de novo. Neurons rely on astrocytic glutamate synthesis, requiring glycogenolysis.

  16. Suprachiasmatic modulation of noradrenaline release in the ventrolateral preoptic nucleus.

    Science.gov (United States)

    Saint-Mleux, Benoît; Bayer, Laurence; Eggermann, Emmanuel; Jones, Barbara E; Mühlethaler, Michel; Serafin, Mauro

    2007-06-13

    As the major brain circadian pacemaker, the suprachiasmatic nucleus (SCN) is known to influence the timing of sleep and waking. We thus investigated here the effect of SCN stimulation on neurons of the ventrolateral preoptic nucleus (VLPO) thought to be involved in promoting sleep. Using an acute in vitro preparation of the rat anterior hypothalamus/preoptic area, we found that whereas single-pulse stimulations of the SCN evoked standard fast ionotropic IPSPs and EPSPs, train stimulations unexpectedly evoked a long-lasting inhibition (LLI). Such LLIs could also be evoked in VLPO neurons by pressure application of NMDA within the SCN, indicating the specific activation of SCN neurons. This LLI was shown to result from the presynaptic facilitation of noradrenaline release, because it was suppressed in presence of yohimbine, a selective antagonist of alpha2-adrenoreceptors. The LLI depended on the opening of a potassium conductance, because it was annulled at E(K) and could be reversed below E(K). These results show that the SCN can provide an LLI of the sleep-promoting VLPO neurons that could play a role in the circadian organization of the sleep-waking cycle.

  17. Differential Activation in Amygdala and Plasma Noradrenaline during Colorectal Distention by Administration of Corticotropin-Releasing Hormone between Healthy Individuals and Patients with Irritable Bowel Syndrome.

    Directory of Open Access Journals (Sweden)

    Yukari Tanaka

    Full Text Available Irritable bowel syndrome (IBS often comorbids mood and anxiety disorders. Corticotropin-releasing hormone (CRH is a major mediator of the stress response in the brain-gut axis, but it is not clear how CRH agonists change human brain responses to interoceptive stimuli. We tested the hypothesis that brain activation in response to colorectal distention is enhanced after CRH injection in IBS patients compared to healthy controls. Brain H215O- positron emission tomography (PET was performed in 16 male IBS patients and 16 age-matched male controls during baseline, no distention, mild and intense distention of the colorectum using barostat bag inflation. Either CRH (2 μg/kg or saline (1:1 was then injected intravenously and the same distention protocol was repeated. Plasma adrenocorticotropic hormone (ACTH, serum cortisol and plasma noradrenaline levels were measured at each stimulation. At baseline, CRH without colorectal distention induced more activation in the right amygdala in IBS patients than in controls. During intense distention after CRH injection, controls showed significantly greater activation than IBS patients in the right amygdala. Plasma ACTH and serum cortisol secretion showed a significant interaction between drug (CRH, saline and distention. Plasma noradrenaline at baseline significantly increased after CRH injection compared to before injection in IBS. Further, plasma noradrenaline showed a significant group (IBS, controls by drug by distention interaction. Exogenous CRH differentially sensitizes brain regions of the emotional-arousal circuitry within the visceral pain matrix to colorectal distention and synergetic activation of noradrenergic function in IBS patients and healthy individuals.

  18. Chronic cobalt-induced epilepsy: noradrenaline ionophoresis and adrenoceptor binding studies in the rat cerebral cortex

    International Nuclear Information System (INIS)

    Bregman, B.; Le Saux, F.; Maurin, Y.; Trottier, S.; Chauvel, P.

    1985-01-01

    Several studies indicate that brain noradrenaline (NA) depletion facilitates the occurrence of epileptogenic syndromes in various animal models. In cobalt-induced epilepsy in the rat, seizure activity is associated with a cortical NA denervation. In order to search for cortical adrenoceptor modifications, inonophoretic studies and adrenoceptor binding assays were performed. At the period of maximal seizure activity, there was a significant supersensitivity of cortial neurons to the ionophoretic application of NA. An increase in the density of β-adrenoceptor binding sites was observed. No modification in α 1 - and α 2 -adrenoceptor binding sites was found. This suggests that in cobalt-induced epilepsy there is a denervation supersensitivity which rests on a selective involvement of β-adrenoceptors. (Author)

  19. Noradrenaline decreases spike voltage threshold and induces electrographic sharp waves in turtle medial cortex in vitro.

    Science.gov (United States)

    Lorenzo, Daniel; Velluti, Julio C

    2004-01-01

    The noradrenergic modulation of neuronal properties has been described at different levels of the mammalian brain. Although the anatomical characteristics of the noradrenergic system are well known in reptiles, functional data are scarce. In our study the noradrenergic modulation of cortical electrogenesis in the turtle medial cortex was studied in vitro using a combination of field and intracellular recordings. Turtle EEG consists of a low voltage background interspersed by spontaneous large sharp waves (LSWs). Noradrenaline (NA, 5-40 microM) induced (or enhanced) the generation of LSWs in a dose-dependent manner. Pharmacological experiments suggest the participation of alpha and beta receptors in this effect. In medial cortex neurons NA induced a hyperpolarization of the resting potential and a decrease of input resistance. Both effects were observed also after TTX treatment. Noradrenaline increased the response of the cells to depolarizing pulses, resulting in an upward shift of the frequency/current relation. In most cells the excitability change was mediated by a decrease of the spike voltage threshold resulting in the reduction of the amount of depolarization needed to fire the cell (voltage threshold minus resting potential). As opposed to the mechanisms reported in mammalian neurons, no changes in the frequency adaptation or the post-train afterhyperpolarization were observed. The NA effects at the cellular level were not reproduced by noradrenergic agonists. Age- and species-dependent properties in the pharmacology of adrenergic receptors could be involved in this result. Cellular effects of NA in turtle cortex are similar to those described in mammals, although the increase in cellular excitability seems to be mediated by a different mechanism. Copyright 2004 S. Karger AG, Basel

  20. Evidence for a dihydropyridine-sensitive and conotoxin-insensitive release of noradrenaline and uptake of calcium in adrenal chromaffin cells.

    Science.gov (United States)

    Owen, P. J.; Marriott, D. B.; Boarder, M. R.

    1989-01-01

    1. It has been suggested that neuronal voltage-sensitive calcium channels (VSCC) may be divided into dihydropyridine (DHP)-sensitive (L) and DHP-insensitive (N and T), and that both the L and the N type channels are attenuated by the peptide blocker omega-conotoxin. Here the effects of omega-conotoxin on release of noradrenaline and uptake of calcium in bovine adrenal chromaffin cells were investigated. 2. Release of noradrenaline in response to 25 mM K+, 65 mM K+, 10 nM bradykinin or 10 microM prostaglandin E1 was not affected by omega-conotoxin in the range 10 nM-1 microM. 3. 45Ca2+ uptake stimulated by high K+ and prostaglandin was attenuated by 1 microM nitrendipine and enhanced by 1 microM Bay K 8644; these calcium fluxes were not modified by 20 nM omega-conotoxin. 4. With superfused rat brain striatal slices in the same medium as the above cell studies, release of dopamine in response to 25 mM K+ was attenuated by 20 nM omega-conotoxin. 5. These results show that in these neurone-like cells, release may be effected by calcium influx through DHP-sensitive but omega-conotoxin-insensitive VSCC, a result inconsistent with the suggestion that omega-conotoxin blocks both L-type and N-type neuronal calcium channels. PMID:2470457

  1. Chronic sleep restriction induces long-lasting changes in adenosine and noradrenaline receptor density in the rat brain.

    Science.gov (United States)

    Kim, Youngsoo; Elmenhorst, David; Weisshaupt, Angela; Wedekind, Franziska; Kroll, Tina; McCarley, Robert W; Strecker, Robert E; Bauer, Andreas

    2015-10-01

    Although chronic sleep restriction frequently produces long-lasting behavioural and physiological impairments in humans, the underlying neural mechanisms are unknown. Here we used a rat model of chronic sleep restriction to investigate the role of brain adenosine and noradrenaline systems, known to regulate sleep and wakefulness, respectively. The density of adenosine A1 and A2a receptors and β-adrenergic receptors before, during and following 5 days of sleep restriction was assessed with autoradiography. Rats (n = 48) were sleep-deprived for 18 h day(-1) for 5 consecutive days (SR1-SR5), followed by 3 unrestricted recovery sleep days (R1-R3). Brains were collected at the beginning of the light period, which was immediately after the end of sleep deprivation on sleep restriction days. Chronic sleep restriction increased adenosine A1 receptor density significantly in nine of the 13 brain areas analysed with elevations also observed on R3 (+18 to +32%). In contrast, chronic sleep restriction reduced adenosine A2a receptor density significantly in one of the three brain areas analysed (olfactory tubercle which declined 26-31% from SR1 to R1). A decrease in β-adrenergic receptors density was seen in substantia innominata and ventral pallidum which remained reduced on R3, but no changes were found in the anterior cingulate cortex. These data suggest that chronic sleep restriction can induce long-term changes in the brain adenosine and noradrenaline receptors, which may underlie the long-lasting neurocognitive impairments observed in chronic sleep restriction. © 2015 European Sleep Research Society.

  2. Effect of an inhibitor of noradrenaline uptake, desipramine, on cell proliferation in the intestinal crypt epithelium.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1989-01-01

    The intestinal mucosa receives an adrenergic innervation for which there is no commonly accepted function. However, in recent years, cell kinetic studies have raised the possibility that this innervation may be an important regulator of crypt cell proliferation. The effects of noradrenaline released from adrenergic nerves is terminated principally by re-uptake of the amine into the nerve and this process can be inhibited by the antidepressant drug, desipramine. In this report desipramine is shown to accelerate crypt cell proliferation in intact, but not in chemically sympathectomized rats, thus adding support to the notion that regulation of crypt cell division is an important function of the sympathetic nervous system.

  3. Critical investigation of the separation of noradrenaline and adrenaline from urine samples using Al2O3 as adsorbant

    International Nuclear Information System (INIS)

    Neidhart, B.; Kringe, K.-P.; Deutschmann, P.

    1983-01-01

    A critical investigation of the separation of free noradrenaline and adrenaline from urine samples revealed serious errors during sample pretreatment using Al 2 O 3 as adsorbent. An exact and rapid pH adjustment of the sample, using thymol-blue as indicator, proved to be the chief prerequisite for precise and accurate results. Increasing temperature and pH favour the oxidative decomposition of the catecholamines during routine analysis. This was examined, using the radiotracer method and liquid scintillation counting. (author)

  4. Increased Contractile Response to Noradrenaline Induced By Factors Associated with the Metabolic Syndrome in Cultured Small Mesenteric Arteries

    DEFF Research Database (Denmark)

    Blædel, Martin; Sams, Anette; Boonen, Harrie C M

    2016-01-01

    UNLABELLED: This study investigated the effect of the metabolic syndrome associated risk factors hyperglycemia (glucose [Glc]), hyperinsulinemia (insulin [Ins]) and low-grade inflammation (tumor necrosis factor α [TNFα]) on the vasomotor responses of resistance arteries. Isolated small mesenteric...... arteries from 3-month-old Sprague-Dawley rats, were suspended for 21-23 h in tissue cultures containing either elevated Glc (30 mmol/l), Ins (100 nmol/l), TNFα (100 ng/ml) or combinations thereof. After incubation, the vascular response to noradrenaline (NA), phenylephrine, isoprenaline and NA...... in vascular tone....

  5. Noradrenaline represses PPAR (peroxisome-proliferator-activated receptor) gamma2 gene expression in brown adipocytes: intracellular signalling and effects on PPARgamma2 and PPARgamma1 protein levels

    DEFF Research Database (Denmark)

    Lindgren, Eva M; Nielsen, Ronni; Petrovic, Natasa

    2004-01-01

    phases, with the highest mRNA levels being found at the time of transition between the phases. PPARgamma2 mRNA levels were downregulated by noradrenaline treatment (EC50, 0.1 microM) in both proliferative and differentiating cells, with a lagtime of 1 h and lasting up to 4 h, after which expression...... was thus to investigate the influence of noradrenaline on PPARgamma gene expression in brown adipocytes. In primary cultures of brown adipocytes, PPARgamma2 mRNA levels were 20-fold higher than PPARgamma1 mRNA levels. PPARgamma expression occurred during both the proliferation and the differentiation...... gradually recovered. The down-regulation was beta-adrenoceptor-induced and intracellularly mediated via cAMP and protein kinase A; the signalling pathway did not involve phosphoinositide 3-kinase, Src, p38 mitogen-activated protein kinase or extracellular-signal-regulated kinases 1 and 2. Treatment...

  6. Dopamine and noradrenaline efflux in the prefrontal cortex in the light and dark period: Effects of novelty and handling and comparison to the nucleus accumbens

    NARCIS (Netherlands)

    Feenstra, M. G.; Botterblom, M. H.; Mastenbroek, S.

    2000-01-01

    We used on-line microdialysis measurements of dopamine and noradrenaline extracellular concentrations in the medial prefrontal cortex of awake, freely moving rats during the dark and the light period of the day to study whether (i) basal efflux would be higher in the active, dark period than in the

  7. The effects of compound stimulus extinction and inhibition of noradrenaline reuptake on the renewal of alcohol seeking

    Science.gov (United States)

    Furlong, T M; Pan, M J; Corbit, L H

    2015-01-01

    Alcohol-related stimuli can trigger relapse of alcohol-seeking behaviors even after extended periods of abstinence. Extinction of such stimuli can reduce their impact on relapse; however, the expression of extinction can be disrupted when testing occurs outside the context where extinction learning took place, an effect termed renewal. Behavioral and pharmacological methods have recently been shown to augment extinction learning; yet, it is not known whether the improved expression of extinction following these treatments remains context-dependent. Here we examined whether two methods, compound–stimulus extinction and treatment with the noradrenaline reuptake inhibitor atomoxetine, would reduce the vulnerability of extinction to a change in context. Following alcohol self-administration, responding was extinguished in a distinct context. After initial extinction, further extinction was given to a target stimulus presented in compound with another alcohol-predictive stimulus intended to augment prediction error (Experiment 1) or after a systemic injection of atomoxetine (1.0 mg kg−1; Experiment 2). A stimulus extinguished as part of a compound elicited less responding than a stimulus receiving equal extinction alone regardless of whether animals were tested in the training or extinction context; however, reliable renewal was not observed in this paradigm. Importantly, atomoxetine enhanced extinction relative to controls even in the presence of a reliable renewal effect. Thus, extinction of alcohol-seeking behavior can be improved by extinguishing multiple alcohol-predictive stimuli or enhancing noradrenaline neurotransmission during extinction training. Importantly, both methods improve extinction even when the context is changed between extinction training and test, and thus could be utilized to enhance the outcome of extinction-based treatments for alcohol-use disorders. PMID:26327688

  8. Central noradrenaline transporter availability in highly obese, non-depressed individuals

    Energy Technology Data Exchange (ETDEWEB)

    Hesse, Swen; Sabri, Osama [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Leipzig University Medical Centre, Integrated Treatment and Research Centre (IFB) Adiposity Diseases, Leipzig (Germany); Becker, Georg-Alexander; Bresch, Anke; Luthardt, Julia; Patt, Marianne; Meyer, Philipp M. [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Rullmann, Michael [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Leipzig University Medical Centre, Integrated Treatment and Research Centre (IFB) Adiposity Diseases, Leipzig (Germany); Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig (Germany); Hankir, Mohammed K.; Zientek, Franziska; Reissig, Georg; Fenske, Wiebke K. [Leipzig University Medical Centre, Integrated Treatment and Research Centre (IFB) Adiposity Diseases, Leipzig (Germany); Arelin, Katrin [Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig (Germany); University of Leipzig, Day Clinic for Cognitive Neurology, Leipzig (Germany); Lobsien, Donald [University of Leipzig, Department of Neuroradiology, Leipzig (Germany); Mueller, Ulrich [University of Cambridge, Department of Psychiatry and Behavioural and Clinical Neuroscience Institute, Cambridge (United Kingdom); Baldofski, S.; Hilbert, Anja [Leipzig University Medical Centre, Integrated Treatment and Research Centre (IFB) Adiposity Diseases, Leipzig (Germany); University of Leipzig, Department of Medical Psychology and Medical Sociology, Leipzig (Germany); Blueher, Matthias [University of Leipzig, Department of Internal Medicine, Leipzig (Germany); Fasshauer, Mathias; Stumvoll, Michael [Leipzig University Medical Centre, Integrated Treatment and Research Centre (IFB) Adiposity Diseases, Leipzig (Germany); University of Leipzig, Department of Internal Medicine, Leipzig (Germany); Ding, Yu-Shin [New York University School of Medicine, Departments of Radiology and Psychiatry, New York, NY (United States)

    2017-06-15

    The brain noradrenaline (NA) system plays an important role in the central nervous control of energy balance and is thus implicated in the pathogenesis of obesity. The specific processes modulated by this neurotransmitter which lead to obesity and overeating are still a matter of debate. We tested the hypothesis that in vivo NA transporter (NAT) availability is changed in obesity by using positron emission tomography (PET) and S,S-[{sup 11}C]O-methylreboxetine (MRB) in twenty subjects comprising ten highly obese (body mass index BMI > 35 kg/m{sup 2}), metabolically healthy, non-depressed individuals and ten non-obese (BMI < 30 kg/m{sup 2}) healthy controls. Overall, we found no significant differences in binding potential (BP{sub ND}) values between obese and non-obese individuals in the investigated brain regions, including the NAT-rich thalamus (0.40 ± 0.14 vs. 0.41 ± 0.18; p = 0.84) though additional discriminant analysis correctly identified individual group affiliation based on regional BP{sub ND} in all but one (control) case. Furthermore, inter-regional correlation analyses indicated different BP{sub ND} patterns between both groups but this did not survive testing for multiple comparions. Our data do not find an overall involvement of NAT changes in human obesity. However, preliminary secondary findings of distinct regional and associative patterns warrant further investigation. (orig.)

  9. Central noradrenaline transporter availability in highly obese, non-depressed individuals

    International Nuclear Information System (INIS)

    Hesse, Swen; Sabri, Osama; Becker, Georg-Alexander; Bresch, Anke; Luthardt, Julia; Patt, Marianne; Meyer, Philipp M.; Rullmann, Michael; Hankir, Mohammed K.; Zientek, Franziska; Reissig, Georg; Fenske, Wiebke K.; Arelin, Katrin; Lobsien, Donald; Mueller, Ulrich; Baldofski, S.; Hilbert, Anja; Blueher, Matthias; Fasshauer, Mathias; Stumvoll, Michael; Ding, Yu-Shin

    2017-01-01

    The brain noradrenaline (NA) system plays an important role in the central nervous control of energy balance and is thus implicated in the pathogenesis of obesity. The specific processes modulated by this neurotransmitter which lead to obesity and overeating are still a matter of debate. We tested the hypothesis that in vivo NA transporter (NAT) availability is changed in obesity by using positron emission tomography (PET) and S,S-["1"1C]O-methylreboxetine (MRB) in twenty subjects comprising ten highly obese (body mass index BMI > 35 kg/m"2), metabolically healthy, non-depressed individuals and ten non-obese (BMI < 30 kg/m"2) healthy controls. Overall, we found no significant differences in binding potential (BP_N_D) values between obese and non-obese individuals in the investigated brain regions, including the NAT-rich thalamus (0.40 ± 0.14 vs. 0.41 ± 0.18; p = 0.84) though additional discriminant analysis correctly identified individual group affiliation based on regional BP_N_D in all but one (control) case. Furthermore, inter-regional correlation analyses indicated different BP_N_D patterns between both groups but this did not survive testing for multiple comparions. Our data do not find an overall involvement of NAT changes in human obesity. However, preliminary secondary findings of distinct regional and associative patterns warrant further investigation. (orig.)

  10. Lead intoxication induces noradrenaline depletion, motor nonmotor disabilities, and changes in the firing pattern of subthalamic nucleus neurons.

    Science.gov (United States)

    Sabbar, M; Delaville, C; De Deurwaerdère, P; Benazzouz, A; Lakhdar-Ghazal, N

    2012-05-17

    Lead intoxication has been suggested as a high risk factor for the development of Parkinson disease. However, its impact on motor and nonmotor functions and the mechanism by which it can be involved in the disease are still unclear. In the present study, we studied the effects of lead intoxication on the following: (1) locomotor activity using an open field actimeter and motor coordination using the rotarod test, (2) anxiety behavior using the elevated plus maze, (3) "depression-like" behavior using sucrose preference test, and (4) subthalamic nucleus (STN) neuronal activity using extracellular single unit recordings. Male Sprague-Dawley rats were treated once a day with lead acetate or sodium acetate (20 mg/kg/d i.p.) during 3 weeks. The tissue content of monoamines was used to determine alteration of these systems at the end of experiments. Results show that lead significantly reduced exploratory activity, locomotor activity and the time spent on the rotarod bar. Furthermore, lead induced anxiety but not "depressive-like" behavior. The electrophysiological results show that lead altered the discharge pattern of STN neurons with an increase in the number of bursting and irregular cells without affecting the firing rate. Moreover, lead intoxication resulted in a decrease of tissue noradrenaline content without any change in the levels of dopamine and serotonin. Together, these results show for the first time that lead intoxication resulted in motor and nonmotor behavioral changes paralleled by noradrenaline depletion and changes in the firing activity of STN neurons, providing evidence consistent with the induction of atypical parkinsonian-like deficits. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Radioenzymatic assay of plasma adrenaline and noradrenaline: evidence for a catechol-O-methyltransferase (COMT) inhibiting factor associated with essential hypertension

    International Nuclear Information System (INIS)

    Hoffmann, J.J.M.L.; Willemsen, J.J.; Thien, Th.; Benraad, Th.J.

    1982-01-01

    During the evaluation of a modified radioenzymatic determination of plasma adrenaline and noradrenaline, it has been found that there exists a highly significant (p 0 C, but only in plasma from patients with essential hypertension. Plasma from normotensive persons exhibits a complete lack of correlation between these factors. The consequences of the hypertension-associated COMT-inhibiting factor for the assays' specifications are discussed and data are presented for comparison with a recently-described uremia-associated COMT-inhibitor (Demassieux et al, Clin Chim Acta 115, 377-391; 1981). (Auth.)

  12. Relationship between respiratory failure and plasma noradrenaline levels in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Yamashita, A; Koike, Y; Takahashi, A; Hirayama, M; Murakami, N; Sobue, G

    1997-08-01

    We evaluated plasma noradrenaline (NA) levels at test and during head-up tilt test in 20 patients with sporadic amyotrophic lateral sclerosis (ALS). Their fasting plasma NA levels ranged from 195 to 4227 pg/ml. The average plasma NA level was 483 pg/ml in five ambulatory patients, 341 in two wheelchair-bound patients, 1264 in 11 bedridden patients, and 208 in two respirator-dependent patients whose disability grading was the worst among the four groups. Arterial carbon dioxide (PCO2) was evaluated as a measure of respiratory function. The coefficient of correlation between PCO2 and plasma NA was r = 0.654 (p respiratory failure or lower motor neuron dysfunction may relate to the elevation of plasma NA levels. In the two bedridden patients, plasma NA levels and heart rate at rest increased significantly as the disease progressed. Cardiovascular responses to head-up tilting were normal. These data suggest that the elevation of plasma NA levels may be related to progression of respiratory failure and lower motor neuron dysfunction. In conclusion, sympathetic hyperactivity in ALS is considered to be not primary, but secondary to somatic motor disabilities and respiratory failure.

  13. Selective potentiation of noradrenaline in the guinea-pig vas deferens by 2-(4-methylaminobutoxy) diphenylmethane hydrochloride (MCI-2016), a new psychotropic drug.

    OpenAIRE

    Ohizumi, Y.; Takahashi, M.; Tobe, A.

    1982-01-01

    In the isolated vas deferens of the guinea-pig, the effects of 2-(4-methylaminobutoxy) diphenylmethane hydrochloride (MCI-2016), a new psychotropic drug, on the contractile response to various agonists or transmural electrical stimulation and on the release of noradrenaline (NA) from the tissue were examined and compared with cocaine. MCI-2016 (3 X 10(-6)M) and cocaine (3 X 10(-5)M) produced a leftward shift (15 and 20 times, respectively) of the dose-response curves for the contractile effec...

  14. Effect of Leu-enkephalin and delta sleep inducing peptide (DSIP) on endogenous noradrenaline release by rat brain synaptosomes

    International Nuclear Information System (INIS)

    Lozhanets, V.V.; Anosov, A.K.

    1986-01-01

    The nonapeptide delta-sleep inducing peptide (DSIP) causes specific changes in the encephalogram of recipient animals: It prolongs the phase of long-wave or delta sleep. The cellular mechanism of action of DSIP has not yet been explained. To test the hyporhesis that this peptide or its degradation product may be presynaptic regulators of catecholamine release, the action of Leu-enkephaline, DSIP, and amino acids composing DSIP on release of endogenous noradrenalin (NA) from synaptosomes during depolarization was compared. Subcellular fractions from cerebral hemisphere of noninbred male albino rats were isolated. Lactate dehydrogenase activity was determined in the suspension of synaptosomes before and after addition of 0.5% Triton X-100. The results were subjected to statistical analysis, using the Wilcoxon-Mann-Whitney nonparametric test

  15. The radioenzymatic determination of adrenaline and noradrenaline in plasma and its use in the diagnostic of pheochromocytomas

    International Nuclear Information System (INIS)

    Neuhaus, C.P.E.

    1982-01-01

    The radioenzymatic determination of adrenaline and noradrenaline in human plasma for the diagnosis of pheochromocytomas was put to use after improvements were made with respect to extraction and separation steps. The plasma catecholamines at rest were distinctly higher in patients with pheochromocytomas. The plasma catecholamine level showed a significant increase as well with the glucagon test between the second and fifth minute. The method was not well suited for the localisation diagnostic where the plasma catecholamines were determined in selectively taken blood from the lower vena cava. Overall, however, the radioenzymatic determination of catecholamines in plasma proved itself to be a relatively ponderous, but exact and sensitive method for the measuring of basal catecholamine level and its changes. In the clinical area it is used as a valuable supplement to the contemporary diagnostic of pheochromocytomas. (orig./TRV) [de

  16. Simultaneous determination of the content of serotonin, dopamine, noradrenaline and adrenaline in pancreatic islets isolated from fed and starved mice

    International Nuclear Information System (INIS)

    Hansen, S.E.; Hedeskov, C.J.

    1977-01-01

    A highly sensitive double isotope method for the simultaneous determination of serotonin, dopamine, noradrenaline and adrenaline has been developed. Advantages and limitations of the method are discussed. The mentioned biogenic amines are all present in isolated pancreatic islet tissue from albino mice in concentrations ranging from approximately 5-30 μmol per kg wet weight (0.8-5 x 10 -3 pmol/ng DNA). A somewhat higher content of these amines, especially dopamine, was found in pancreatic acinar tissue. The hypothesis that the impaired glucose-induced insulin secretion during starvation partly is caused by an increased content of biogenic amines in the pancreatic islets was not supported by our experiments which showed an unchanged islet content of these amines after 48 h starvation. (author)

  17. Simultaneous determination of the content of serotonin, dopamine, noradrenaline and adrenaline in pancreatic islets isolated from fed and starved mice

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, S E; Hedeskov, C J [Copenhagen Univ. (Denmark)

    1977-01-01

    A highly sensitive double isotope method for the simultaneous determination of serotonin, dopamine, noradrenaline and adrenaline has been developed. Advantages and limitations of the method are discussed. The mentioned biogenic amines are all present in isolated pancreatic islet tissue from albino mice in concentrations ranging from approximately 5-30 ..mu..mol per kg wet weight (0.8-5 x 10/sup -3/ pmol/ng DNA). A somewhat higher content of these amines, especially dopamine, was found in pancreatic acinar tissue. The hypothesis that the impaired glucose-induced insulin secretion during starvation partly is caused by an increased content of biogenic amines in the pancreatic islets was not supported by our experiments which showed an unchanged islet content of these amines after 48 h starvation.

  18. Noradrenaline and dopamine neurons in the reward/effort trade-off: a direct electrophysiological comparison in behaving monkeys.

    Science.gov (United States)

    Varazzani, Chiara; San-Galli, Aurore; Gilardeau, Sophie; Bouret, Sebastien

    2015-05-20

    Motivation determines multiple aspects of behavior, including action selection and energization of behavior. Several components of the underlying neural systems have been examined closely, but the specific role of the different neuromodulatory systems in motivation remains unclear. Here, we compare directly the activity of dopaminergic neurons from the substantia nigra pars compacta and noradrenergic neurons from the locus coeruleus in monkeys performing a task manipulating the reward/effort trade-off. Consistent with previous reports, dopaminergic neurons encoded the expected reward, but we found that they also anticipated the upcoming effort cost in connection with its negative influence on action selection. Conversely, the firing of noradrenergic neurons increased with both pupil dilation and effort production in relation to the energization of behavior. Therefore, this work underlines the contribution of dopamine to effort-based decision making and uncovers a specific role of noradrenaline in energizing behavior to face challenges. Copyright © 2015 the authors 0270-6474/15/357866-12$15.00/0.

  19. Fluxes of lactate into, from, and among gap junction-coupled astrocytes and their interaction with noradrenaline

    Directory of Open Access Journals (Sweden)

    Leif eHertz

    2014-09-01

    Full Text Available Lactate is a versatile metabolite with important roles in modulation of brain glucose utilization rate (CMRglc, diagnosis of brain-injured patients, redox- and receptor-mediated signaling, memory, and alteration of gene transcription. Neurons and astrocytes release and accumulate lactate using equilibrative monocarboxylate transporters that carry out net transmembrane transport of lactate only until intra- and extracellular levels reach equilibrium. Astrocytes have much faster lactate uptake than neurons and shuttle more lactate among gap junction-coupled astrocytes than to nearby neurons. Lactate diffusion within syncytia can provide precursors for oxidative metabolism and glutamate synthesis and facilitate its release from endfeet to perivascular space to stimulate blood flow. Lactate efflux from brain during activation underlies the large underestimation of CMRglc with labeled glucose and fall in CMRO2/CMRglc ratio. Receptor-mediated effects of lactate on locus coeruleus neurons include noradrenaline release in cerebral cortex and c-AMP-mediated stimulation of astrocytic gap junctional coupling, thereby enhancing its dispersal and release from brain. Lactate transport is essential for its multifunctional roles.

  20. Genesis and Maintenance of Attentional Biases: The Role of the Locus Coeruleus-Noradrenaline System

    Directory of Open Access Journals (Sweden)

    Mana R. Ehlers

    2017-01-01

    Full Text Available Emotionally arousing events are typically better remembered than mundane ones, in part because emotionally relevant aspects of our environment are prioritized in attention. Such biased attentional tuning is itself the result of associative processes through which we learn affective and motivational relevance of cues. We propose that the locus coeruleus-noradrenaline (LC-NA system plays an important role in the genesis of attentional biases through associative learning processes as well as their maintenance. We further propose that individual differences in and disruptions of the LC-NA system underlie the development of maladaptive biases linked to psychopathology. We provide support for the proposed role of the LC-NA system by first reviewing work on attentional biases in development and its link to psychopathology in relation to alterations and individual differences in NA availability. We focus on pharmacological manipulations to demonstrate the effect of a disrupted system as well as the ADRA2b polymorphism as a tool to investigate naturally occurring differences in NA availability. We next review associative learning processes that—modulated by the LC-NA system—result in such implicit attentional biases. Further, we demonstrate how NA may influence aversive and appetitive conditioning linked to anxiety disorders as well as addiction and depression.

  1. Copper Induces Vasorelaxation and Antagonizes Noradrenaline -Induced Vasoconstriction in Rat Mesenteric Artery

    Directory of Open Access Journals (Sweden)

    Yu-Chun Wang

    2013-11-01

    Full Text Available Background/Aims: Copper is an essential trace element for normal cellular function and contributes to critical physiological or pathological processes. The aim of the study was to investigate the effects of copper on vascular tone of rat mesenteric artery and compare the effects of copper on noradrenaline (NA and high K+ induced vasoconstriction. Methods: The rat mesenteric arteries were isolated and the vessel tone was measured by using multi wire myograph system in vitro. Blood pressure of carotid artery in rabbits was measured by using physiological data acquisition and analysis system in vivo. Results: Copper dose-dependently blunted NA-induced vasoconstriction of rat mesenteric artery. Copper-induced vasorelaxation was inhibited when the vessels were pretreated with NG-nitro-L-arginine methyl ester (L-NAME. Copper did not blunt high K+-induced vasoconstriction. Copper preincubation inhibited NA-evoked vasoconstriction and the inhibition was not affected by the presence of L-NAME. Copper preincubation showed no effect on high K+-evoked vasoconstriction. Copper chelator diethyldithiocarbamate trihydrate (DTC antagonized the vasoactivity induced by copper in rat mesenteric artery. In vivo experiments showed that copper injection (iv significantly decreased blood pressure of rabbits and NA or DTC injection (iv did not rescue the copper-induced hypotension and animal death. Conclusion: Copper blunted NA but not high K+-induced vasoconstriction of rat mesenteric artery. The acute effect of copper on NA-induced vasoconstriction was depended on nitric oxide (NO, but the effect of copper pretreatment on NA-induced vasoconstriction was independed on NO, suggesting that copper affected NA-induced vasoconstriction by two distinct mechanisms.

  2. Volume Transmission in Central Dopamine and Noradrenaline Neurons and Its Astroglial Targets.

    Science.gov (United States)

    Fuxe, Kjell; Agnati, Luigi F; Marcoli, Manuela; Borroto-Escuela, Dasiel O

    2015-12-01

    Already in the 1960s the architecture and pharmacology of the brainstem dopamine (DA) and noradrenaline (NA) neurons with formation of vast numbers of DA and NA terminal plexa of the central nervous system (CNS) indicated that they may not only communicate via synaptic transmission. In the 1980s the theory of volume transmission (VT) was introduced as a major communication together with synaptic transmission in the CNS. VT is an extracellular and cerebrospinal fluid transmission of chemical signals like transmitters, modulators etc. moving along energy gradients making diffusion and flow of VT signals possible. VT interacts with synaptic transmission mainly through direct receptor-receptor interactions in synaptic and extrasynaptic heteroreceptor complexes and their signaling cascades. The DA and NA neurons are specialized for extrasynaptic VT at the soma-dendrtitic and terminal level. The catecholamines released target multiple DA and adrenergic subtypes on nerve cells, astroglia and microglia which are the major cell components of the trophic units building up the neural-glial networks of the CNS. DA and NA VT can modulate not only the strength of synaptic transmission but also the VT signaling of the astroglia and microglia of high relevance for neuron-glia interactions. The catecholamine VT targeting astroglia can modulate the fundamental functions of astroglia observed in neuroenergetics, in the Glymphatic system, in the central renin-angiotensin system and in the production of long-distance calcium waves. Also the astrocytic and microglial DA and adrenergic receptor subtypes mediating DA and NA VT can be significant drug targets in neurological and psychiatric disease.

  3. Effect of naftopidil on brain noradrenaline-induced decrease in arginine-vasopressin secretion in rats

    Directory of Open Access Journals (Sweden)

    Masaki Yamamoto

    2016-09-01

    Full Text Available Naftopidil, an α1-adrenoceptor antagonist, has been shown to inhibit nocturnal polyuria in patients with lower urinary tract symptom. However, it remains unclear how naftopidil decreases nocturnal urine production. Here, we investigated the effects of naftopidil on arginine-vasopressin (AVP plasma level and urine production and osmolality in rats centrally administered with noradrenaline (NA. NA (3 or 30 μg/kg was administered into the left ventricle (i.c.v. of male Wistar rats 3 h after naftopidil pretreatment (10 or 30 mg/kg, i.p.. Blood samples were collected from the inferior vena cava 1 h after NA administration or 4 h after peritoneal administration of naftopidil; plasma levels of AVP were assessed by ELISA. Voiding behaviors of naftopidil (30 mg/kg, i.p.-administered male Wistar rats were observed during separate light- and dark cycles. Administration of NA decreased plasma AVP levels and elevated urine volume, which were suppressed by systemic pretreatment with naftopidil (30 mg/kg, i.p.. Urine osmolality decreased 1 h after NA administration. However, naftopidil by itself had no effect on plasma AVP levels or urodynamic parameters during light- and dark cycles. Our findings suggest that systemic administration of naftopidil could prevent central noradrenergic nervous system-mediated decline in AVP secretion and increase in urine production in rats.

  4. Toxicity of noradrenaline, a novel anti-biofouling component, to two non-target zooplankton species, Daphnia magna and Ceriodaphnia dubia.

    Science.gov (United States)

    Overturf, C L; Wormington, A M; Blythe, K N; Gohad, N V; Mount, A S; Roberts, A P

    2015-05-01

    Noradrenaline (NA) is the active component of novel antifouling agents and acts by preventing attachment of fouling organisms. The goal of this study was to examine the toxicity of NA to the non-target zooplankton D. magna and C. dubia. Neonates were exposed to one of five concentrations of NA and effects on survival, reproduction and molting were determined. Calculated LC50 values were determined to be 46 and 38 μM in C. dubia and D. magna, respectively. A 10-day C. dubia study found that reproduction metrics were significantly impacted at non-lethal concentrations. In D. magna, concentrations greater than 40 μM significantly impacted molting. A toxicity test was conducted with D. magna using oxidized NA, which yielded similar results. These data indicate that both NA and oxidized NA are toxic to non-target zooplankton. Results obtained from this study can be used to guide future ecological risk assessments of catecholamine-based antifouling agents. Copyright © 2015. Published by Elsevier Inc.

  5. Serotonin and noradrenaline reuptake inhibitors (SNRIs) for fibromyalgia.

    Science.gov (United States)

    Welsch, Patrick; Üçeyler, Nurcan; Klose, Petra; Walitt, Brian; Häuser, Winfried

    2018-02-28

    Fibromyalgia is a clinically defined chronic condition of unknown etiology characterized by chronic widespread pain that often co-exists with sleep disturbances, cognitive dysfunction and fatigue. People with fibromyalgia often report high disability levels and poor quality of life. Drug therapy, for example, with serotonin and noradrenaline reuptake inhibitors (SNRIs), focuses on reducing key symptoms and improving quality of life. This review updates and extends the 2013 version of this systematic review. To assess the efficacy, tolerability and safety of serotonin and noradrenaline reuptake inhibitors (SNRIs) compared with placebo or other active drug(s) in the treatment of fibromyalgia in adults. For this update we searched CENTRAL, MEDLINE, Embase, the US National Institutes of Health and the World Health Organization (WHO) International Clinical Trials Registry Platform for published and ongoing trials and examined the reference lists of reviewed articles, to 8 August 2017. We selected randomized, controlled trials of any formulation of SNRIs against placebo or any other active treatment of fibromyalgia in adults. Three review authors independently extracted data, examined study quality, and assessed risk of bias. For efficacy, we calculated the number needed to treat for an additional beneficial outcome (NNTB) for pain relief of 50% or greater and of 30% or greater, patient's global impression to be much or very much improved, dropout rates due to lack of efficacy, and the standardized mean differences (SMD) for fatigue, sleep problems, health-related quality of life, mean pain intensity, depression, anxiety, disability, sexual function, cognitive disturbances and tenderness. For tolerability we calculated number needed to treat for an additional harmful outcome (NNTH) for withdrawals due to adverse events and for nausea, insomnia and somnolence as specific adverse events. For safety we calculated NNTH for serious adverse events. We undertook meta

  6. Quantified distribution of the noradrenaline innervation in the hippocampus of adult rat

    International Nuclear Information System (INIS)

    Oleskevich, S.; Descarries, L.; Lacaille, J.C.

    1989-01-01

    A recently developed radioautographic technique, based on the uptake labeling of monoamine terminals in vitro, was used to quantify the noradrenaline (NA) innervation in adult rat hippocampus. After incubation of brain slices with 1 microM 3H-NA, the NA varicosities were visualized as small aggregates of silver grains, in light microscope radioautographs prepared at 3 equidistant horizontal levels across the ventral 2/3 of the hippocampus. Using a computer-assisted image analyzer, counts were obtained from the subiculum (SUB), 3 sectors of Ammon's horn (CA1, CA3-a, CA3-b) and 3 sectors of the dentate gyrus (DG-medial blade, crest, and lateral blade), every lamina being sampled in each region. After a double correction for duration of radioautographic exposure and section thickness, and following measurement of varicosity diameter in electron microscope radioautographs, it was possible to express these results in number of terminals per volumetric unit of tissue. It was thus found that the overall density of hippocampal NA innervation averages 2.1 million varicosities/mm3 of tissue, a value almost twice as high as that in cerebral cortex. This innervation is 20% denser ventrally than dorsally and is heterogeneous both in terms of regional and laminar distribution. SUB and DG are more strongly innervated than Ammon's horn, wherein CA1 has the lowest overall density. In SUB and CA1, there is a clear predilection of NA varicosities for the stratum moleculare. In CA3, there is a narrow band of even stronger innervation in the stratum radiatum, near the apical border of the stratum pyramidale, contrasting with a 3 times lower density in this cell layer and the stratum oriens. In DG, the NA innervation is again the weakest in the cell body layer and exhibits an almost 3-fold greater density in the polymorph layer, the highest of all hippocampus

  7. Increase in serum noradrenaline concentration by short dives with bradycardia in Indo-Pacific bottlenose dolphin Tursiops aduncus.

    Science.gov (United States)

    Suzuki, Miwa; Tomoshige, Mika; Ito, Miki; Koga, Sotaro; Yanagisawa, Makio; Bungo, Takashi; Makiguchi, Yuya

    2017-07-01

    In cetaceans, diving behavior immediately induces a change in blood circulation to favor flow to the brain and heart; this is achieved by intense vasoconstriction of the blood vessels that serve other organs. This blood circulation response is allied to a decrease in heart rate in order to optimize oxygen usage during diving. Vasoconstrictors are present in all mammals and stimulate the contraction of the smooth muscle in the walls of blood vessels. The most important of these vasoconstrictors are the hormones adrenaline (A), noradrenaline (NA), and angiotensin II (ANG II). At present, the contribution of these hormones to vasoconstriction during diving in cetaceans is unclear. To elucidate their possible roles, changes in serum levels of A, NA and ANG II were monitored together with heart rate in the Indo-Pacific bottlenose dolphin Tursiops aduncus during 90 and 180s dives. Both brief diving periods induced an increase in serum NA concentration and a decrease in heart rate; however, no changes were detected in serum levels of A or ANG II. These data indicate that NA may play a role in diving-induced vasoconstriction. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Extinction memory is facilitated by methylphenidate and regulated by dopamine and noradrenaline receptors.

    Science.gov (United States)

    Furini, Cristiane R G; Behling, Jonny A K; Zinn, Carolina G; Zanini, Mara Lise; Assis Brasil, Eduardo; Pereira, Luiza Doro; Izquierdo, Ivan; de Carvalho Myskiw, Jociane

    2017-05-30

    Extinction is defined as the learned inhibition of retrieval and is the mainstay of exposure therapy, which is widely used to treat drug addiction, phobias and fear disorders. The psychostimulant, methylphenidate (MPH) is known to increase extracellular levels of noradrenaline and dopamine by blocking their reuptake and studies have demonstrated that MPH can modulate hippocampal physiology and/or functions including long-term potentiation (LTP), learning and memory. However, the influence of MPH on fear extinction memory has been insufficiently studied. Here we investigate the effect of MPH infused into the CA1 region of the hippocampus on extinction memory in animals normally incapable of showing contextual fear conditioning (CFC) extinction because of weak training, and the possible mechanisms through which it acts during this process. For this, male Wistar rats with infusion cannulae stereotaxically implanted in the CA1 region were submitted to a weak extinction protocol in a CFC apparatus. Animals that received intra-CA1 infusion of MPH (12.5μg/side) 20min before the extinction training (Ext Tr) expressed less freezing behavior than Veh-treated animals during both Ext Tr and extinction retention Test (Ext Test). Additionally, the administration of MPH+Timolol (1μg/side) or MPH+SCH23390 (1.5μg/side) intra-CA1 20min before the Ext Tr blocked the enhancing effect of the MPH on extinction learning. These results suggest that MPH in the CA1 region of the hippocampus is able to induce the consolidation of extinction memory and this process occurs through both β-adrenergic and D1/D5 dopaminergic receptors. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Analysis of microdialysate monoamines, including noradrenaline, dopamine and serotonin, using capillary ultra-high performance liquid chromatography and electrochemical detection.

    Science.gov (United States)

    Ferry, Barbara; Gifu, Elena-Patricia; Sandu, Ioana; Denoroy, Luc; Parrot, Sandrine

    2014-03-01

    Electrochemical methods are very often used to detect catecholamine and indolamine neurotransmitters separated by conventional reverse-phase high performance liquid chromatography (HPLC). The present paper presents the development of a chromatographic method to detect monoamines present in low-volume brain dialysis samples using a capillary column filled with sub-2μm particles. Several parameters (repeatability, linearity, accuracy, limit of detection) for this new ultrahigh performance liquid chromatography (UHPLC) method with electrochemical detection were examined after optimization of the analytical conditions. Noradrenaline, adrenaline, serotonin, dopamine and its metabolite 3-methoxytyramine were separated in 1μL of injected sample volume; they were detected above concentrations of 0.5-1nmol/L, with 2.1-9.5% accuracy and intra-assay repeatability equal to or less than 6%. The final method was applied to very low volume dialysates from rat brain containing monoamine traces. The study demonstrates that capillary UHPLC with electrochemical detection is suitable for monitoring dialysate monoamines collected at high sampling rate. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Noradrenaline and acetylcholine responsiveness of glucose-monitoring and glucose-insensitive neurons in the mediodorsal prefrontal cortex.

    Science.gov (United States)

    Nagy, Bernadett; Szabó, István; Csetényi, Bettina; Hormay, Edina; Papp, Szilárd; Keresztes, Dóra; Karádi, Zoltán

    2014-01-16

    The mediodorsal prefrontal cortex (mdPFC), as part of the forebrain glucose-monitoring (GM) system, plays important role in several regulatory processes to control the internal state of the organism and to initiate behavioral outputs accordingly. Little is known, however, about the neurochemical sensitivity of neurons located in this area. Substantial evidence indicates that the locus ceruleus - noradrenaline (NA) projection system and the nucleus basalis magnocellularis - cholinergic projection system regulate behavioral state and state dependent processing of sensory information, various cognitive functions already associated with the mdPFC. The main goal of the present study was to examine noradrenergic and cholinergic responsiveness of glucose-monitoring and glucose-insensitive (GIS) neurons in the mediodorsal prefrontal cortex. One fifth of the neurons tested changed in firing rate to microelectrophoretically applied NA. Responsiveness of the GM cells to this catecholamine proved to be significantly higher than that of the GIS units. Microiontophoretic application of acetylcholine (Ach) resulted in activity changes (predominantly facilitation) of more than 40% of the mdPFC neurons. Proportion of Ach sensitive units among the GM and the GIS neurons was found to be similar. The glucose-monitoring neurons of the mdPFC and their distinct NA and remarkable Ach sensitivity are suggested to be of particular significance in prefrontal control of adaptive behaviors. © 2013 Published by Elsevier B.V.

  11. Noradrenaline increases the expression and release of Hsp72 by human neutrophils.

    Science.gov (United States)

    Giraldo, E; Multhoff, G; Ortega, E

    2010-05-01

    The blood concentration of extracellular 72kDa heat shock protein (eHsp72) increases under conditions of stress, including intense exercise. However, the signal(s), source(s), and secretory pathways in its release into the bloodstream have yet to be clarified. The aim of the present study was to evaluate the role of noradrenaline (NA) as a stress signal on the expression and release of Hsp72 by circulating neutrophils (as a source), all within a context of the immunophysiological regulation during exercise-induced stress in sedentary and healthy young (21-26years) women. The expression of Hsp72 on the surface of isolated neutrophils was determined by flow cytometry, and its release by cultured isolated neutrophils was determined by ELISA. Incubation with cmHsp70-FITC showed that neutrophils express Hsp72 on their surface under basal conditions. In addition, cultured isolated neutrophils (37 degrees C and 5% CO(2)) also released Hsp72 under basal conditions, with this release increasing from 10min to 24h in the absence of cell damage. NA at 10(-9)-10(-5)M doubled the percentage of neutrophils expressing Hsp72 after 60min and 24h incubation. NA also stimulated (by about 20%) the release of Hsp72 after 10min of incubation. (1) Hsp72 is expressed on the surface of isolated neutrophils under basal conditions, and this expression is augmented by NA. (2) Isolated neutrophils can also release Hsp72 under cultured basal conditions in the absence of cell death, and NA can increase this release. These results may contribute to confirming the hypothesis that NA can act as a "stress signal" for the increased eHsp72 in the context of exercise stress, with a role for neutrophils as a source for the expression and, to a lesser degree, the release of Hsp72 after activation by NA. Copyright 2010 Elsevier Inc. All rights reserved.

  12. Five Patients With Burning Mouth Syndrome in Whom an Antidepressant (Serotonin-Noradrenaline Reuptake Inhibitor) Was Not Effective, but Pregabalin Markedly Relieved Pain.

    Science.gov (United States)

    Ito, Mikiko; Tokura, Tatsuya; Yoshida, Keizo; Nagashima, Wataru; Kimura, Hiroyuki; Umemura, Eri; Tachibana, Masako; Miyauchi, Tomoya; Kobayashi, Yuka; Arao, Munetaka; Ozaki, Norio; Kurita, Kenichi

    2015-01-01

    Burning mouth syndrome (BMS) causes idiopathic pain or a burning sensation in clinically normal oral mucosa. Burning mouth syndrome is a chronic disease with an unknown etiology. Burning mouth syndrome is also idiopathic, and a consensus regarding diagnosis/treatment has not been reached yet. Recent studies have supported the suggestion that BMS is a neuropathic pain disorder in which both the peripheral and central nervous systems are involved. Tricyclic antidepressants (nortriptyline and amitriptyline), serotonin-noradrenaline reuptake inhibitors (SNRIs) (duloxetine and milnacipran), and antiepileptic drugs, potential-dependent calcium channel α2δ subunit ligands (gabapentine and pregabalin), are currently recommended as the first-choice drugs for neuropathic pain. In this study, we report 5 patients with BMS in whom there was no response to SNRI (milnacipran or duloxetine), or administration was discontinued because of adverse reactions, but in whom pregabalin therapy markedly reduced or led to the disappearance of pain in a short period. Pregabalin, whose mechanism of action differs from that of SNRIs, may become a treatment option for BMS patients who are not responsive to or are resistant to SNRIs.

  13. Effects of Acetylcholine and Noradrenalin on Action Potentials of Isolated Rabbit Sinoatrial and Atrial Myocytes

    Science.gov (United States)

    Verkerk, Arie O.; Geuzebroek, Guillaume S. C.; Veldkamp, Marieke W.; Wilders, Ronald

    2012-01-01

    The autonomic nervous system controls heart rate and contractility through sympathetic and parasympathetic inputs to the cardiac tissue, with acetylcholine (ACh) and noradrenalin (NA) as the chemical transmitters. In recent years, it has become clear that specific Regulators of G protein Signaling proteins (RGS proteins) suppress muscarinic sensitivity and parasympathetic tone, identifying RGS proteins as intriguing potential therapeutic targets. In the present study, we have identified the effects of 1 μM ACh and 1 μM NA on the intrinsic action potentials of sinoatrial (SA) nodal and atrial myocytes. Single cells were enzymatically isolated from the SA node or from the left atrium of rabbit hearts. Action potentials were recorded using the amphotericin-perforated patch-clamp technique in the absence and presence of ACh, NA, or a combination of both. In SA nodal myocytes, ACh increased cycle length and decreased diastolic depolarization rate, whereas NA decreased cycle length and increased diastolic depolarization rate. Both ACh and NA increased maximum upstroke velocity. Furthermore, ACh hyperpolarized the maximum diastolic potential. In atrial myocytes stimulated at 2 Hz, both ACh and NA hyperpolarized the maximum diastolic potential, increased the action potential amplitude, and increased the maximum upstroke velocity. Action potential duration at 50 and 90% repolarization was decreased by ACh, but increased by NA. The effects of both ACh and NA on action potential duration showed a dose dependence in the range of 1–1000 nM, while a clear-cut frequency dependence in the range of 1–4 Hz was absent. Intermediate results were obtained in the combined presence of ACh and NA in both SA nodal and atrial myocytes. Our data uncover the extent to which SA nodal and atrial action potentials are intrinsically dependent on ACh, NA, or a combination of both and may thus guide further experiments with RGS proteins. PMID:22754533

  14. [Changes in serotonin and noradrenaline in hepatic encephalopathy as a result of liver failure in rat].

    Science.gov (United States)

    Song, Min-ning; Song, Yu-na; Chen, Fu; Luo, Mei-lan

    2007-01-01

    To investigate the changes in serotonin (5-HT) and noradrenaline (NA) in hepatic encephalopathy as a result of acute and chronic liver failure in rat. One hundred and ten Sprague-Dawley (SD) rats were randomly divided into groups of normal control (n=20), experimental group of acute liver failure (ALF) encephalopathy (n=45), and experimental group of chronic liver failure (CLF) encephalopathy (n=45). Two dosages of thioacetamide (TAA) of 500 mg/kg were gavaged with an interval of 24 hours to reproduce ALF model. To reproduce CLF model rats were fed with 0.03% TAA in drinking water for 10 weeks, and 50% of TAA dosage was added or withheld according to the change in weekly body weight measurement. Animals were sacrificed and venous blood specimens were obtained after successful replication of model, and 5-HT, NA, ammonia, parameters of liver function were determined, and liver and brain were studied pathologically. The experiment showed that the liver functions of rats in groups ALF encephalopathy and CLF encephalopathy deteriorated seriously, changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumen (ALB), ALB/globulin (A/G), and blood ammonia were observed(Pliver and brain pathologies were identical to those of ALF and CLF encephalopathy. The values of 5-HT were increased in groups ALF encephalopathy and CLF encephalopathy [(16.06+/-1.08) micromol/L and (15.32+/-1.48) micromol/L] compared with the normal group [(2.75+/-0.26) micromol/L, both Pencephalopathy [(94.0+/-2.13) pmol/L vs.(121.2+/-14.8) pmol/L,Pencephalopathy and CLF encephalopathy. The content of NA decreases remarkably in CLF encephalopathy.

  15. Serotonin noradrenaline reuptake inhibitors: New hope for the treatment of chronic pain.

    Science.gov (United States)

    Delgado, Pedro L

    2006-01-01

    Depression and painful symptoms occur frequently together. Over 75% of depressed patients report painful symptoms such as headache, stomach pain, neck and back pain as well as non-specific generalized pain. In addition, World Health Organization data have shown that primary care patients with chronic pain have a four fold greater risk of becoming depressed than pain-free patients. Increasingly, pain is considered as an integral symptom of depression and there evidence to suggest that pain and depression may arise from a common neurobiological dysfunction. Serotonergic cell bodies, in the raphe nucleus, and noradrenergic cell bodies in the locus coeruleus send projections to various parts of the brain, where they are involved in the control of mood, movement, cognitive functioning and emotions. In addition both serotonergic and noradrenergic neurons project to the spinal cord. These descending pathways serve to inhibit input from the intestines, skeletal muscles and other sensory inputs. Usually, these inhibitory effects are modest, but in times of stress, in the interest of the survival of the individual, they can completely inhibit the input from painful stimuli. A dysfunction of the serotonergic and noradrenergic neurons can thus affect both the ascending and descending pathways resulting in the psychological symptoms of depression and somatic pain symptoms such as chronic pain, fibromyalgia, non-cardiac chest pain, or irritable bowel syndrome. In view of this, it is not surprising that tricyclic antidepressants have been a standard treatment of chronic pain for many years. In contrast and in spite of their improved tolerance, selective serotonin reuptake inhibitors do not appear to be particularly effective in the treatment of pain. Recently, a number of open and controlled trials with selective serotonin and noradrenaline reuptake inhibitors such as venlafaxine, milnacipran and duloxetine, suggest that these compounds may be more effective in relieving pain

  16. Steroidogenic disruptive effects of the serotonin-noradrenaline reuptake inhibitors duloxetine, venlafaxine and tramadol in the H295R cell assay and in a recombinant CYP17 assay

    DEFF Research Database (Denmark)

    Islin, Julie; Munkboel, Cecilie Hurup; Styrishave, Bjarne

    2018-01-01

    The aim of this study was to determine the steroidogenic endocrine disrupting effect of the three most widely used serotonin-noradrenaline reuptake inhibitors duloxetine, venlafaxine and tramadol, using two in vitro models, the H295R assay and a recombinant CYP17 enzyme assay. Steroid hormones were...... quantified using LC-MS/MS. Duloxetine showed endocrine disrupting effects at 5-20μM with CYP17 being the main target. Venlafaxine also affected the steroidogenesis, mainly by affecting the CYP17 lyase reaction, although at much higher concentrations i.e. 100μM. Tramadol only exerted minor effects...... on the steroidogenesis with the lowest observed effect at 314μM. Based on the H295R results, the inhibition of CYP17 by duloxetine and venlafaxine was investigated in a recombinant CYP17 assay with the use of the 4 major CYP17 substrates pregnenolone, progesterone, 17α-hydroxypregnenolone and 17α...

  17. Dopamine, Noradrenaline and Serotonin Receptor Densities in the Striatum of Hemiparkinsonian Rats following Botulinum Neurotoxin-A Injection.

    Science.gov (United States)

    Mann, T; Zilles, K; Dikow, H; Hellfritsch, A; Cremer, M; Piel, M; Rösch, F; Hawlitschka, A; Schmitt, O; Wree, A

    2018-03-15

    Parkinson's disease (PD) is characterized by a degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) that causes a dopamine (DA) deficit in the caudate-putamen (CPu) accompanied by compensatory changes in other neurotransmitter systems. These changes result in severe motor and non-motor symptoms. To disclose the role of various receptor binding sites for DA, noradrenaline, and serotonin in the hemiparkinsonian (hemi-PD) rat model induced by unilateral 6-hydroxydopamine (6-OHDA) injection, the densities of D 1 , D 2 /D 3 , α 1 , α 2 , and 5HT 2A receptors were longitudinally visualized and measured in the CPu of hemi-PD rats by quantitative in vitro receptor autoradiography. We found a moderate increase in D 1 receptor density 3 weeks post lesion that decreased during longer survival times, a significant increase of D 2 /D 3 receptor density, and 50% reduction in 5HT 2A receptor density. α 1 receptor density remained unaltered in hemi-PD and α 2 receptors demonstrated a slight right-left difference increasing with post lesion survival. In a second step, the possible role of receptors on the known reduction of apomorphine-induced rotations in hemi-PD rats by intrastriatally injected Botulinum neurotoxin-A (BoNT-A) was analyzed by measuring the receptor densities after BoNT-A injection. The application of this neurotoxin reduced D 2 /D 3 receptor density, whereas the other receptors mainly remained unaltered. Our results provide novel data for an understanding of the postlesional plasticity of dopaminergic, noradrenergic and serotonergic receptors in the hemi-PD rat model. The results further suggest a therapeutic effect of BoNT-A on the impaired motor behavior of hemi-PD rats by reducing the interhemispheric imbalance in D 2 /D 3 receptor density. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Characterization of noradrenaline release in the locus coeruleus of freely moving awake rats by in vivo microdialysis.

    Science.gov (United States)

    Fernández-Pastor, Begoña; Mateo, Yolanda; Gómez-Urquijo, Sonia; Javier Meana, J

    2005-07-01

    The origin and regulation of noradrenaline (NA) in the locus coeruleus (LC) is unknown. The neurochemical features of NA overflow (nerve impulse dependence, neurotransmitter synthesis, vesicle storage, reuptake, alpha2-adrenoceptor-mediated regulation) were characterized in the LC. Brain microdialysis was performed in awake rats. Dialysates were analyzed for NA. NA in the LC decreased via local infusion of Ca2+-free medium (-42+/-5%) or the sodium channel blocker tetrodotoxine (TTX) (-47+/-8%) but increased (333+/-40%) via KCl-induced depolarization. The tyrosine hydroxylase (TH) inhibitor alpha-methyl-p-tyrosine (250 mg kg(-1), i.p.) and the vesicle depletory drug reserpine (5 mg kg(-1), i.p.) decreased NA. Therefore, extracellular NA in the LC satisfies the criteria for an impulse flow-dependent vesicular exocytosis of neuronal origin. Local perfusion of the alpha2-adrenoceptor agonist clonidine (0.1-100 microM) decreased NA (E(max)=-79+/-5%) in the LC, whereas the opposite effect (E(max)=268+/-53%) was observed with the alpha2A-adrenoceptor antagonist BRL44408 (0.1-100 microM). This suggests a tonic modulation of NA release through local alpha2A-adrenoceptors. The selective NA reuptake inhibitor desipramine (DMI) (0.1-100 microM) administered into the LC increased NA in the LC (E(max)=223+/-40%) and simultaneously decreased NA in the cingulate cortex, confirming the modulation exerted by NA in the LC on firing activity of noradrenergic cells and on the subsequent NA release in noradrenergic terminals. Synaptic processes underlying NA release in the LC are similar to those in noradrenergic terminal areas. NA in the LC could represent local somatodendritic release, but also the presence of neurotransmitter release from collateral axon terminals.

  19. Mercuric chloride-induced alterations of levels of noradrenaline, dopamine, serotonin and acetylcholine esterase activity in different regions of rat brain during postnatal development

    Energy Technology Data Exchange (ETDEWEB)

    Lakshmana, M.K. (Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore (India)); Desiraju, T. (Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore (India)); Raju, T.R. (Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore (India))

    1993-07-01

    Wistar rats were fed mercuric chloride, 4 mg/kg body weight per day chronically from postnatal day 2 to 60 by gastric intubation. Mercury consumption was then discontinued until 170 days to allow time for recovery. Since mercury caused reduction in body weight, an underweight group was also included besides the normal saline group. Levels of noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT) and the activity of acetylcholine esterase (AChE) were assayed in various brain regions in different age groups. By 60 days of age, the mercury group showed elevations of NA levels in olfactory bulb (OB), visual cortex (VC) and brain stem (BS) but not in striatumaccumbens (SA) and hippocampus (HI). DA levels were also increased in OB, HI, VC and BS but not in SA. AChE activity was decreased in the mercury group only in HI and VC at 20 days of age. The Mercury group showed no behavioural abnormality outwardly; however, operant conditioning relevated a dificiency in performance. Nevertheless, all these changes disappeared after discontinuation of mercury intake. Thus the changes occurring in the brain at this level of oral mercuric chloride intake seem to reflect adaptive neural mechanisms rather than pathological damage. (orig.)

  20. Regarding the unitary theory of agonist and antagonist action at presynaptic adrenoceptors.

    Science.gov (United States)

    Kalsner, S; Abdali, S A

    2001-06-01

    1. The linkage between potentiation of field stimulation-induced noradrenaline release and blockade of the presynaptic inhibitory effect of exogenous noradrenaline by a presynaptic antagonist was examined in superfused rabbit aorta preparations. 2. Rauwolscine clearly potentiated the release of noradrenaline in response to 100 pulses at 2 Hz but reduced the capacity of noradrenaline to inhibit transmitter release to a questionable extent, and then only when comparisons were made with untreated, rather then to rauwolscine-treated, controls. 3. Aortic preparations exposed for 60 min to rauwolscine followed by superfusion with antagonist-free Krebs for 60 min retained the potentiation of stimulation-induced transmitter release but no antagonism of the noradrenaline-induced inhibition could be detected at either of two noradrenaline concentrations when comparisons were made with rauwolscine treated controls. 4. Comparisons of the inhibitory effect of exogenous noradrenaline (1.8 x 10-6 M) on transmitter efflux in the presence and absence of rauwolscine pretreatment revealed that the antagonist enhanced rather than antagonized the presynaptic inhibition by noradrenaline. 5 It is concluded that the unitary hypothesis that asserts that antagonist enhancement of transmitter release and its blockade of noradrenaline induced inhibition are manifestations of a unitary event are not supportable.

  1. Activation of β-adrenergic receptors is required for elevated α1A-adrenoreceptors expression and signaling in mesenchymal stromal cells

    Science.gov (United States)

    Tyurin-Kuzmin, Pyotr A.; Fadeeva, Julia I.; Kanareikina, Margarita A.; Kalinina, Natalia I.; Sysoeva, Veronika Yu.; Dyikanov, Daniyar T.; Stambolsky, Dmitriy V.; Tkachuk, Vsevolod A.

    2016-01-01

    Sympathetic neurons are important components of mesenchymal stem cells (MSCs) niche and noradrenaline regulates biological activities of these cells. Here we examined the mechanisms of regulation of MSCs responsiveness to noradrenaline. Using flow cytometry, we demonstrated that α1A adrenergic receptors isoform was the most abundant in adipose tissue-derived MSCs. Using calcium imaging in single cells, we demonstrated that only 6.9 ± 0.8% of MSCs responded to noradrenaline by intracellular calcium release. Noradrenaline increases MSCs sensitivity to catecholamines in a transitory mode. Within 6 hrs after incubation with noradrenaline the proportion of cells responding by Ca2+ release to the fresh noradrenaline addition has doubled but declined to the baseline after 24 hrs. Increased sensitivity was due to the elevated quantities of α1A-adrenergic receptors on MSCs. Such elevation depended on the stimulation of β-adrenergic receptors and adenylate cyclase activation. The data for the first time clarify mechanisms of regulation of MSCs sensitivity to noradrenaline. PMID:27596381

  2. Dgroup: DG01455 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 212 ... Norepinephrine ... D00076 ... Noradrenaline (JP17); Norepinephrine (INN) ... D05206 ... Norepinephrine bitartr...USP); Isoprenaline sulfate (JAN) ... D02150 ... l-Isoprenaline hydrochloride (JP17) ... DG00212 ... Norepinephrine ... D00076 ... Noradrenaline...DG00212 ... Norepinephrine ... D00076 ... Noradrenaline (JP17); Norepinephrine (INN) ...

  3. Serotonin, dopamine and noradrenaline adjust actions of myelinated afferents via modulation of presynaptic inhibition in the mouse spinal cord.

    Directory of Open Access Journals (Sweden)

    David L García-Ramírez

    Full Text Available Gain control of primary afferent neurotransmission at their intraspinal terminals occurs by several mechanisms including primary afferent depolarization (PAD. PAD produces presynaptic inhibition via a reduction in transmitter release. While it is known that descending monoaminergic pathways complexly regulate sensory processing, the extent these actions include modulation of afferent-evoked PAD remains uncertain. We investigated the effects of serotonin (5HT, dopamine (DA and noradrenaline (NA on afferent transmission and PAD. Responses were evoked by stimulation of myelinated hindlimb cutaneous and muscle afferents in the isolated neonatal mouse spinal cord. Monosynaptic responses were examined in the deep dorsal horn either as population excitatory synaptic responses (recorded as extracellular field potentials; EFPs or intracellular excitatory postsynaptic currents (EPSCs. The magnitude of PAD generated intraspinally was estimated from electrotonically back-propagating dorsal root potentials (DRPs recorded on lumbar dorsal roots. 5HT depressed the DRP by 76%. Monosynaptic actions were similarly depressed by 5HT (EFPs 54%; EPSCs 75% but with a slower time course. This suggests that depression of monosynaptic EFPs and DRPs occurs by independent mechanisms. DA and NA had similar depressant actions on DRPs but weaker effects on EFPs. IC50 values for DRP depression were 0.6, 0.8 and 1.0 µM for 5HT, DA and NA, respectively. Depression of DRPs by monoamines was nearly-identical in both muscle and cutaneous afferent-evoked responses, supporting a global modulation of the multimodal afferents stimulated. 5HT, DA and NA produced no change in the compound antidromic potentials evoked by intraspinal microstimulation indicating that depression of the DRP is unrelated to direct changes in the excitability of intraspinal afferent fibers, but due to metabotropic receptor activation. In summary, both myelinated afferent-evoked DRPs and monosynaptic

  4. Noradrenaline from Locus Coeruleus Neurons Acts on Pedunculo-Pontine Neurons to Prevent REM Sleep and Induces Its Loss-Associated Effects in Rats.

    Science.gov (United States)

    Khanday, Mudasir Ahmad; Somarajan, Bindu I; Mehta, Rachna; Mallick, Birendra Nath

    2016-01-01

    Normally, rapid eye movement sleep (REMS) does not appear during waking or non-REMS. Isolated, independent studies showed that elevated noradrenaline (NA) levels inhibit REMS and induce REMS loss-associated cytomolecular, cytomorphological, psychosomatic changes and associated symptoms. However, the source of NA and its target in the brain for REMS regulation and function in health and diseases remained to be confirmed in vivo . Using tyrosine hydroxylase (TH)-siRNA and virus-coated TH-shRNA in normal freely moving rats, we downregulated NA synthesis in locus coeruleus (LC) REM-OFF neurons in vivo . These TH-downregulated rats showed increased REMS, which was prevented by infusing NA into the pedunculo-pontine tegmentum (PPT), the site of REM-ON neurons, normal REMS returned after recovery. Moreover, unlike normal or control-siRNA- or shRNA-injected rats, upon REMS deprivation (REMSD) TH-downregulated rat brains did not show elevated Na-K ATPase (molecular changes) expression and activity. To the best of our knowledge, these are the first in vivo findings in an animal model confirming that NA from the LC REM-OFF neurons (1) acts on the PPT REM-ON neurons to prevent appearance of REMS, and (2) are responsible for inducing REMSD-associated molecular changes and symptoms. These observations clearly show neuro-physio-chemical mechanism of why normally REMS does not appear during waking. Also, that LC neurons are the primary source of NA, which in turn causes some, if not many, REMSD-associated symptoms and behavioral changes. The findings are proof-of-principle for the first time and hold potential to be exploited for confirmation toward treating REMS disorder and amelioration of REMS loss-associated symptoms in patients.

  5. Brief note about plasma catecholamines kinetics and submaximal exercise in untrained standardbreds

    Directory of Open Access Journals (Sweden)

    Paolo Baragli

    2010-03-01

    Full Text Available Four untrained standardbred horses performed a standardized exercise test on the treadmill and an automated blood collection system programmed to obtain blood samples every 15 s was used for blood collection in order to evaluate the kinetics of adrenaline and noradrenaline. The highest average values obtained for adrenaline and noradrenaline were 15.0 ± 3.0 and 15.8 ± 2.8 nmol/l respectively, with exponential accumulation of adrenaline (r = 0.977 and noradrenaline (r = 0.976 during the test. Analysis of the correlation between noradrenaline and adrenaline for each phase of the test shows that correlation coefficient decreases as the intensity of exercise increases (from r = 0.909 to r = 0.788. This suggests that during submaximal exercise, the process for release, distribution and clearance of adrenaline into blood circulation differs from that of noradrenaline.

  6. AcEST: BP921832 [AcEST

    Lifescience Database Archive (English)

    Full Text Available 3975|SC6A2_HUMAN Sodium-dependent noradrenaline transporter OS=Homo sapiens Align...lue sp|P23975|SC6A2_HUMAN Sodium-dependent noradrenaline transporter... 31 2.1 sp...|Q6DEL1|S38A7_DANRE Putative sodium-coupled neutral amino acid... 30 4.7 >sp|P23975|SC6A2_HUMAN Sodium-dependent noradrenaline

  7. Presynaptic beta-adrenoceptors in guinea pig papillary muscle: evidence for adrenaline-mediated positive feedback on noradrenergic transmission

    International Nuclear Information System (INIS)

    Valenta, B.; Singer, E.A.

    1991-01-01

    Guinea pig papillary muscles were preincubated in the presence of 5 x 10 - 9 mol/L unlabeled noradrenaline or adrenaline then incubated with ( 3 H)-noradrenaline and superfused. Electrical field stimulation with 180 pulses delivered at 1 or 3 Hz was used to induce overflow of radioactivity. Comparison of the effects of preexposure of the tissue to adrenaline or noradrenaline revealed that adrenaline incubation caused an enhancement of stimulation-evoked overflow of ( 3 H)noradrenaline and a reduction of the effect of exogenously added isoprenaline. Furthermore, the selective beta 2-adrenoceptor antagonist ICI 118,551 (10 - 7 mol/L), but not the selective beta 1-adrenoceptor antagonist ICI 89,406 (10 - 7 mol/L), reduced electrically evoked overflow of ( 3 H)noradrenaline in tissue preincubated with adrenaline but not in tissue preincubated with noradrenaline. The overflow-reducing effect of ICI 118.551 occurred at stimulation with 3 Hz but not at stimulation with 1 Hz. The present results support the hypothesis that noradrenergic transmission in guinea pig papillary muscle is facilitated via beta 2-adrenoceptors, and that adrenaline may serve as transmitter in this positive feedback mechanism after its incorporation into sympathetic nerves

  8. Cholinergic, noradrenergic and GABAergic control of sexual behaviour

    DEFF Research Database (Denmark)

    Nedergaard, Per

    2000-01-01

    acethylcholine, noradrenalin, GABA, sexual dysfunction, erectile dysfunction, rat, human, male, female......acethylcholine, noradrenalin, GABA, sexual dysfunction, erectile dysfunction, rat, human, male, female...

  9. Effects of articaine on [3H]noradrenaline release from cortical and spinal cord slices prepared from normal and streptozotocin-induced diabetic rats and compared to lidocaine.

    Science.gov (United States)

    Végh, D; Somogyi, A; Bányai, D; Lakatos, M; Balogh, M; Al-Khrasani, M; Fürst, S; Vizi, E S; Hermann, P

    2017-10-01

    Since a significant proportion of diabetic patients have clinical or subclinical neuropathy, there may be concerns about the use of local anaesthetics. The present study was designed to determine and compare the effects of articaine, a widely used anaesthetic in dental practice, and lidocaine on the resting and axonal stimulation-evoked release of [ 3 H]noradrenaline ([ 3 H]NA) in prefrontal cortex slices and the release of [ 3 H]NA in spinal cord slices prepared from non-diabetic and streptozocin (STZ)-induced diabetic (glucose level=22.03±2.31mmol/l) rats. The peak of allodynia was achieved 9 weeks after STZ-treatment. Articaine and lidocaine inhibited the stimulation-evoked release in a concentration-dependent manner and increased the resting release by two to six times. These effects indicate an inhibitory action of these anaesthetics on Na + - and K + -channels. There was no difference in clinically important nerve conduction between non-diabetic and diabetic rats, as measured by the release of transmitter in response to axonal stimulation. The uptake and resting release of NA was significantly higher in the brain slices prepared from diabetic rats, but there were no differences in the spinal cord. For the adverse effects, the effects of articaine on K + channels (resting release) are more pronounced compared to lidocaine. In this respect, articaine has a thiophene ring with high lipid solubility, which may present potential risks for some patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Membrane potential and conductance of frog skin gland acinar cells in resting conditions and during stimulation with agonists of macroscopic secretion

    DEFF Research Database (Denmark)

    Sørensen, Jakob B.; Larsen, Erik Hviid

    1999-01-01

    Adrenaline; carbachol; Cl- secretion; exocrine gland; isoproterenol; noradrenaline; prostaglandin E*U2......Adrenaline; carbachol; Cl- secretion; exocrine gland; isoproterenol; noradrenaline; prostaglandin E*U2...

  11. Dual interaction of agmatine with the rat α2D-adrenoceptor: competitive antagonism and allosteric activation

    Science.gov (United States)

    Molderings, G J; Menzel, S; Kathmann, M; Schlicker, E; Göthert, M

    2000-01-01

    In segments of rat vena cava preincubated with [3H]-noradrenaline and superfused with physiological salt solution, the influence of agmatine on the electrically evoked [3H]-noradrenaline release, the EP3 prostaglandin receptor-mediated and the α2D-adrenoceptor-mediated inhibition of evoked [3H]-noradrenaline release was investigated. Agmatine (0.1–10 μM) by itself was without effect on evoked [3H]-noradrenaline release. In the presence of 10 μM agmatine, the prostaglandin E2(PGE2)-induced EP3-receptor-mediated inhibition of [3H]-noradrenaline release was not modified, whereas the α2D-adrenoceptor-mediated inhibition of [3H]-noradrenaline release induced by noradrenaline, moxonidine or clonidine was more pronounced than in the absence of agmatine. However, 1 mM agmatine antagonized the moxonidine-induced inhibition of [3H]-noradrenaline release. Agmatine concentration-dependently inhibited the binding of [3H]-clonidine and [3H]-rauwolscine to rat brain cortex membranes (Ki values 6 μM and 12 μM, respectively). In addition, 30 and 100 μM agmatine increased the rate of association and decreased the rate of dissociation of [3H]-clonidine resulting in an increased affinity of the radioligand for the α2D-adrenoceptors. [14C]-agmatine labelled specific binding sites on rat brain cortex membranes. In competition experiments. [14C]-agmatine was inhibited from binding to its specific recognition sites by unlabelled agmatine, but not by rauwolscine and moxonidine. In conclusion, the present data indicate that agmatine both acts as an antagonist at the ligand recognition site of the α2D-adrenoceptor and enhances the effects of α2-adrenoceptor agonists probably by binding to an allosteric binding site of the α2D-adrenoceptor which seems to be labelled by [14C]-agmatine. PMID:10928978

  12. Studies concerning the effect of X-rays on electrolytic shifts and on the metabolism of the myocardium. Pt. 6

    International Nuclear Information System (INIS)

    Prignitz, R.; Saurbier, B.; Hoffmeister, G.

    1976-01-01

    In the myocardium of guinea-pigs, the behaviour of the catecholamines noradrenalin and adrenalin as well as the monoamine oxidase activity was biochemically studied following a local irradiation with 250 up to 6,000 R surface dose. The noradrenalin content is significantly reduced already after a surface dose of 250 R. This drop of the noradrenalin content is beginning 15 min after irradiation, and not till 72 hours later, a complete normalization of the noradrenalin content is to be shown. A fractionated irradiation with twice 250 R SD in an interval of 24 hours leads to a further reduction. The changes of the adrenalin content are uncharacteristic, the activity of the monoamine oxidase is unaffected. (orig.) [de

  13. Dopamine, Noradrenaline and Differences in Sexual Behavior between Roman High and Low Avoidance Male Rats: A Microdialysis Study in the Medial Prefrontal Cortex.

    Science.gov (United States)

    Sanna, Fabrizio; Bratzu, Jessica; Piludu, Maria A; Corda, Maria G; Melis, Maria R; Giorgi, Osvaldo; Argiolas, Antonio

    2017-01-01

    Roman High- (RHA) and Low-Avoidance (RLA) outbred rats, which differ for a respectively rapid vs. poor acquisition of the active avoidance response in the shuttle-box, display differences in sexual activity when put in the presence of a sexually receptive female rat. Indeed RHA rats show higher levels of sexual motivation and copulatory performance than RLA rats, which persist also after repeated sexual activity. These differences have been correlated to a higher tone of the mesolimbic dopaminergic system of RHA rats vs. RLA rats, revealed by the higher increase of dopamine found in the dialysate obtained from the nucleus accumbens of RHA than RLA rats during sexual activity. This work shows that extracellular dopamine and noradrenaline (NA) also, increase in the dialysate from the medial prefrontal cortex (mPFC) of male RHA and RLA rats put in the presence of an inaccessible female rat and more markedly during direct sexual interaction. Such increases in dopamine (and its main metabolite 3,4-dihydroxyphenylacetic acid, DOPAC) and NA were found in both sexually naïve and experienced animals, but they were higher: (i) in RHA than in RLA rats; and (ii) in sexually experienced RHA and RLA rats than in their naïve counterparts. Finally, the differences in dopamine and NA in the mPFC occurred concomitantly to those in sexual activity, as RHA rats displayed higher levels of sexual motivation and copulatory performance than RLA rats in both the sexually naïve and experienced conditions. These results suggest that a higher dopaminergic tone also occurs in the mPFC, together with an increased noradrenergic tone, which may be involved in the different copulatory patterns found in RHA and RLA rats, as suggested for the mesolimbic dopaminergic system.

  14. The influence of μ-opioid and noradrenaline reuptake inhibition in the modulation of pain responsive neurones in the central amygdala by tapentadol in rats with neuropathy

    Science.gov (United States)

    Gonçalves, Leonor; Friend, Lauren V.; Dickenson, Anthony H.

    2015-01-01

    Treatments for neuropathic pain are either not fully effective or have problematic side effects. Combinations of drugs are often used. Tapentadol is a newer molecule that produces analgesia in various pain models through two inhibitory mechanisms, namely central μ-opioid receptor (MOR) agonism and noradrenaline reuptake inhibition. These two components interact synergistically, resulting in levels of analgesia similar to opioid analgesics such as oxycodone and morphine, but with more tolerable side effects. The right central nucleus of the amygdala (CeA) is critical for the lateral spinal ascending pain pathway, regulates descending pain pathways and is key in the emotional-affective components of pain. Few studies have investigated the pharmacology of limbic brain areas in pain models. Here we determined the actions of systemic tapentadol on right CeA neurones of animals with neuropathy and which component of tapentadol contributes to its effect. Neuronal responses to multimodal peripheral stimulation of animals with spinal nerve ligation or sham surgery were recorded before and after two doses of tapentadol. After the higher dose of tapentadol either naloxone or yohimbine were administered. Systemic tapentadol resulted in dose-dependent decrease in right CeA neuronal activity only in neuropathy. Both naloxone and yohimbine reversed this effect to an extent that was modality selective. The interactions of the components of tapentadol are not limited to the synergy between the MOR and α2-adrenoceptors seen at spinal levels, but are seen at this supraspinal site where suppression of responses may relate to the ability of the drug to alter affective components of pain. PMID:25576174

  15. A conformational study of protonated noradrenaline by UV-UV and IR dip double resonance laser spectroscopy combined with an electrospray and a cold ion trap method.

    Science.gov (United States)

    Wako, Hiromichi; Ishiuchi, Shun-Ichi; Kato, Daichi; Féraud, Géraldine; Dedonder-Lardeux, Claude; Jouvet, Christophe; Fujii, Masaaki

    2017-05-03

    The conformer-selected ultraviolet (UV) and infrared (IR) spectra of protonated noradrenaline were measured using an electrospray/cryogenic ion trap technique combined with photo-dissociation spectroscopy. By comparing the UV photo dissociation (UVPD) spectra with the UV-UV hole burning (HB) spectra, it was found that five conformers coexist under ultra-cold conditions. Based on the spectral features of the IR dip spectra of each conformer, two different conformations on the amine side chain were identified. Three conformers (group I) were assigned to folded and others (group II) to extended structures by comparing the observed IR spectra with the calculated ones. Observation of the significantly less-stable extended conformers strongly suggests that the extended structures are dominant in solution and are detected in the gas phase by kinetic trapping. The conformers in each group are assignable to rotamers of OH orientations in the catechol ring. By comparing the UV-UV HB spectra and the calculated Franck-Condon spectra obtained by harmonic vibrational analysis of the S 1 state, with the aid of relative stabilization energies of each conformer in the S 0 state, the absolute orientations of catechol OHs of the observed five conformers were successfully determined. It was found that the 0-0 transition of one folded conformer is red-shifted by about 1000 cm -1 from the others. The significant red-shift was explained by a large contribution of the πσ* state to S 1 in the conformer in which an oxygen atom of the meta-OH group is close to the ammonium group.

  16. Disease: H01005 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available eries of mutations in the DBH gene encoding the key enzyme in noradrenaline synth...esis. Nervous system disease DBH [HSA:1621] [KO:K00503] ... Complete absence of noradrenaline and adrenaline

  17. Dgroup: DG01450 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ne hydrochloride (JAN) ... D02149 ... Epinephrine bitartrate (JAN/USP) ... DG00212 ... Norepinephrine ... D00076 ... Noradrenaline...rine hydrochloride (JAN) ... D02149 ... Epinephrine bitartrate (JAN/USP) ... DG00212 ... Norepinephrine ... D00076 ... Noradrenaline

  18. Raynaud's phenomenon

    DEFF Research Database (Denmark)

    Nielsen, S L; Christensen, N J; Olsen, N

    1980-01-01

    . The forearm venous concentration of noradrenaline was lower and adrenaline concentration higher in the sympathectomized patients than in the other groups (p less than 0,05). Noradrenaline showed a significant increase during body cooling in normals and primary Raynaud's (p less than 0......The reaction to body and finger cooling was recorded in seven patients with relapse of primary Raynaud's phenomenon after sufficiently performed bilateral upper thoracic sympathectomy and for comparison in eight young women with primary Raynaud's phenomenon as well as in seven normal women......,05). There was no significant correlation between the vasoconstrictor response to cooling of a finger and the noradrenaline concentration probably due to the fact that skin vasoconstriction impeded release of noradrenaline from the skin. The relapse of Raynaud's phenomenon after surgically sufficient sympathectomy could...

  19. The concentration of adrenaline and noradrenaline in the serum of dogs under the influence of calcium channels blockers

    Directory of Open Access Journals (Sweden)

    Milanović Tamara

    2015-01-01

    membrane of presynaptic ending is necessary to free the neurotransmitter out of the vesicle, the aim of our work is to study whether Verapamile has effects on the membrane of presynaptic endings of sympathetic nervous system checking the level of catecholamine in serum. The experiment was conducted in 6 healthy dogs which were, after 10-minute-infusion (0.9% NaCl, treated with intravenous bolus veramapile injections in three occasions, in every 5 minutes, until the first signs of intoxication had appeared. This caused bradycardia, heart rhythm disorder and blood pressure drop. In order to determine the level of catecholamine, blood was taken sequentially, in every 5 minutes, before the new dose of verapamile was given. Verapamile (given intravenous significantly decreases the concentration of adrenaline and noradrenaline in the serum of dogs.

  20. desensitisation and calcium-sensitivity in the isolated perfused rat ...

    African Journals Online (AJOL)

    Dr Olaleye

    -induced desensitisation to noradrenaline were studied in the isolated perfused rat tail artery. Responses to the activators noradrenaline (NA). (3μM) and potassium chloride (KCl) (100mM) were obtained in Ca2+-buffered saline. Activators ...

  1. Noradrenergic System and Memory

    KAUST Repository

    Zenger, Manuel; Burlet-Godinot, Sophie; Petit, Jean-Marie; Magistretti, Pierre J.

    2017-01-01

    There is ample evidence indicating that noradrenaline plays an important role in memory mechanisms. Noradrenaline is thought to modulate these procsses through activation of adrenergic receptors in neurons. Astrocytes that form essential partners for synaptic function, also express alpha- and beta-adrenergic receptors. In astrocytes, noradrenaline triggers metabolic actions such as the glycogenolysis leading to an increase in l-lactate formation and release. l-Lactate can be used by neurons as a sourc of energy during memory tasks and can also induc transcription of plasticity genes in neurons. Activation of β-adrenergic receptors can also trigger gliotransmitter release resulting of intracllular calcium waves. These gliotransmitters modulate the synaptic activity and thereby can modulate long-term potentiation mechanisms. In summary, recnt evidencs indicate that noradrenaline exerts its memory-promoting effects through different modes of action both on neurons and astrocytes.

  2. Noradrenergic System and Memory

    KAUST Repository

    Zenger, Manuel

    2017-07-22

    There is ample evidence indicating that noradrenaline plays an important role in memory mechanisms. Noradrenaline is thought to modulate these procsses through activation of adrenergic receptors in neurons. Astrocytes that form essential partners for synaptic function, also express alpha- and beta-adrenergic receptors. In astrocytes, noradrenaline triggers metabolic actions such as the glycogenolysis leading to an increase in l-lactate formation and release. l-Lactate can be used by neurons as a sourc of energy during memory tasks and can also induc transcription of plasticity genes in neurons. Activation of β-adrenergic receptors can also trigger gliotransmitter release resulting of intracllular calcium waves. These gliotransmitters modulate the synaptic activity and thereby can modulate long-term potentiation mechanisms. In summary, recnt evidencs indicate that noradrenaline exerts its memory-promoting effects through different modes of action both on neurons and astrocytes.

  3. AcEST: BP913708 [AcEST

    Lifescience Database Archive (English)

    Full Text Available ial protein cyt-4 OS=Neurospora c... 32 1.3 sp|P23975|SC6A2_HUMAN Sodium-dependent nora...drenaline transporter... 30 4.9 sp|O55192|SC6A2_MOUSE Sodium-dependent noradrenaline transporter... 29...+ Sbjct: 237 LLLCLMVVVIVLYFSLWKGVKTSGKVVWITATLPYFV 273 >sp|O55192|SC6A2_MOUSE Sodium-dependent nora...RERHA-------KTLANI 982 Query: 183 N--NKALFQALV 212 + N+ + QALV Sbjct: 983 DGRNELILQALV 994 >sp|P23975|SC6A2_...HUMAN Sodium-dependent noradrenaline transporter OS=Homo sapiens GN=SLC6A2 PE=1 S

  4. The effects of C-type natriuretic peptide on catecholamine release in the pacific spiny dogfish (Squalus acanthias).

    Science.gov (United States)

    Montpetit, C J; McKendry, J; Perry, S F

    2001-08-01

    The interaction between homologous C-type natriuretic peptide (dfCNP) and catecholamine release in cardiovascular control was assessed in the marine dogfish (Squalus acanthias). This was accomplished by evaluation of the dynamics of the dfCNP-elicited secretion of catecholamines in situ and in vivo. With an in situ saline-perfused postcardinal sinus preparation, it was demonstrated that perfusion with saline containing dfCNP (10(-9) mol x L(-1)) did not affect the secretion of either noradrenaline or adrenaline. However, the presence of dfCNP in the perfusate significantly enhanced carbachol-evoked secretion of noradrenaline. In vivo, intravascular injection of dfCNP (10(-9) mol x kg(-1)) caused a biphasic pressor-depressor response consisting of a brief increase in caudal artery blood pressure (P(CA)) followed by a prolonged reduction in P(CA). Furthermore, although systemic resistance initially increased, it was subsequently maintained at baseline values in the face of persistent decreases in both P(CA) and cardiac output. Bolus injection of dfCNP elicited significant increases in plasma noradrenaline levels that peaked within 10 min; plasma adrenaline levels were unaffected. The release of noradrenaline elicited by dfCNP was unaffected by prior blockade of the renin-angiotensin system (RAS) (with the angiotensin converting enzyme inhibitor lisinopril) or by pretreatment with the nicotinic receptor blocker hexamethonium. The delayed decrease in P(CA) was not observed in the hexamethonium-treated fish. Prior blockade of beta-adrenoreceptors (with sotalol) or alpha-adrenoreceptors (with prazosin) either significantly reduced (sotalol) or abolished (prazosin) the increase in plasma noradrenaline levels after dfCNP injection. The results of this investigation demonstrate that the elevation of plasma noradrenaline levels observed in vivo following dfCNP injection is not caused by a direct effect of dfCNP on catecholamine secretion from axillary body chromaffin cells

  5. Raynaud's phenomenon: peripheral catecholamine concentration and effect of sympathectomy.

    Science.gov (United States)

    Nielsen, S L; Christensen, N J; Olsen, N; Lassen, N A

    1980-01-01

    The reaction to body and finger cooling was recorded in seven patients with relapse of primary Raynaud's phenomenon after sufficiently performed bilateral upper thoracic sympathectomy and for comparison in eight young women with primary Raynaud's phenomenon as well as in seven normal women. The forearm venous concentration of noradrenaline was lower and adrenaline concentration higher in the sympathectomized patients than in the other groups (p less than 0,05). Noradrenaline showed a significant increase during body cooling in normals and primary Raynaud's (p less than 0,05). There was no significant correlation between the vasoconstrictor response to cooling of a finger and the noradrenaline concentration probably due to the fact that skin vasoconstriction impeded release of noradrenaline from the skin. The relapse of Raynaud's phenomenon after surgically sufficient sympathectomy could not be treated by reserpine or alfa-adrenergic receptor blockers in two patients in whom this was tried.

  6. [Changes in the monoamine content in different parts of hypothalamus depending on the stages of the estrous cycle].

    Science.gov (United States)

    Babichev, V N; Adamskaia, E I

    1976-01-01

    Fluorimetric determination of monoamines in various regions of the hypothalamus and at different stages of the estral cycle in rats showed that the serotonin, noradrenaline, and particularly dophamine content changed both in the course of the cycle and at different time (10, 15 and 18 hours) of the same stage of the cycle. Dophamine concentration in the arcuate area--the centre of the tonic activity--reached its maximum at 18 hours of the diestrus-2 (D2) and fell to the minimum at 10 hours of the proestrus (P). Noradrenaline level in the preoptic area increased at 18 hours of the D2 and fell at 10 hours of the P. It is supposed that in the hypothalamic regulation of the estral cycle at least two monoamines (dopamine and noradrenaline) took part; the trigger role belongs to noradrenaline of the preoptic area (the cyclic centre).

  7. Spinal mechanism of micturition reflex inhibition by naftopidil in rats.

    Science.gov (United States)

    Sugaya, Kimio; Nishijima, Saori; Kadekawa, Katsumi; Ashitomi, Katsuhiro; Ueda, Tomoyuki; Yamamoto, Hideyuki

    2014-10-29

    We investigated the spinal mechanism through which naftopidil inhibits the micturition reflex by comparing the effects of noradrenaline and naftopidil in rats. The following were investigated: the influence of oral naftopidil on plasma monoamine and amino acid levels, the distribution of oral 14C-naftopidil, the effects of intravenous (IV) or intrathecal (IT) injection of noradrenaline or naftopidil on isovolumetric bladder contractions, amino acid levels in the lumbosacral spinal cord after IT noradrenaline or naftopidil, and the effects of IT naftopidil and strychnine and/or bicuculline on isovolumetric bladder contractions. Oral naftopidil decreased the plasma adrenaline level, while it increased the serotonin and glycine levels. After oral administration, 14C-naftopidil was detected in the spinal cord and cerebrum, as well as in plasma and the prostate gland. When the bladder volume was below the threshold for isovolumetric reflex contractions, IV (0.1mg) or IT (0.1μg) noradrenaline evoked bladder contractions, but IV (1mg) or IT (0.01-1μg) naftopidil did not. When the bladder volume was above the threshold for isovolumetric reflex contractions, IV or IT noradrenaline transiently abolished bladder contractions. IT noradrenaline decreased the levels of glycine and gamma-aminobutyric acid (GABA) in the lumbosacral cord, while IT naftopidil increased the GABA level. IT strychnine and/or bicuculline blocked the inhibitory effect of IT naftopidil on bladder contractions. Naftopidil inhibits the micturition reflex by blocking α1 receptors, as well as by the activation of serotonergic, glycinergic, and GABAergic neurons in the central nervous system. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Stress and emotional memory : a matter of timing

    NARCIS (Netherlands)

    Joëls, Marian; Fernandez, Guillen; Roozendaal, Benno

    Stressful events activate the amygdala and a network of associated brain regions. Studies in both humans and rodents indicate that noradrenaline has a prominent role in this activation. Noradrenaline induces a hypervigilant state that helps to remember the event. This mnemonic effect is enhanced

  9. Co-release of noradrenaline and dopamine in the cerebral cortex elicited by single train and repeated train stimulation of the locus coeruleus

    Directory of Open Access Journals (Sweden)

    Saba Pierluigi

    2005-05-01

    Full Text Available Abstract Background Previous studies by our group suggest that extracellular dopamine (DA and noradrenaline (NA may be co-released from noradrenergic nerve terminals in the cerebral cortex. We recently demonstrated that the concomitant release of DA and NA could be elicited in the cerebral cortex by electrical stimulation of the locus coeruleus (LC. This study analyses the effect of both single train and repeated electrical stimulation of LC on NA and DA release in the medial prefrontal cortex (mPFC, occipital cortex (Occ, and caudate nucleus. To rule out possible stressful effects of electrical stimulation, experiments were performed on chloral hydrate anaesthetised rats. Results Twenty min electrical stimulation of the LC, with burst type pattern of pulses, increased NA and DA both in the mPFC and in the Occ. NA in both cortices and DA in the mPFC returned to baseline within 20 min after the end of the stimulation period, while DA in the Occ reached a maximum increase during 20 min post-stimulation and remained higher than baseline values at 220 min post-stimulation. Local perfusion with tetrodotoxin (TTX, 10 μM markedly reduced baseline NA and DA in the mPFC and Occ and totally suppressed the effect of electrical stimulation in both areas. A sequence of five 20 min stimulations at 20 min intervals were delivered to the LC. Each stimulus increased NA to the same extent and duration as the first stimulus, whereas DA remained elevated at the time next stimulus was delivered, so that baseline DA progressively increased in the mPFC and Occ to reach about 130 and 200% the initial level, respectively. In the presence of the NA transport (NAT blocker desipramine (DMI, 100 μM, multiple LC stimulation still increased extracellular NA and DA levels. Electrical stimulation of the LC increased NA levels in the homolateral caudate nucleus, but failed to modify DA level. Conclusion The results confirm and extend that LC stimulation induces a concomitant

  10. Blood pressure and mesenteric blood flow in the rat during infusion of biogenic amines. Influence of a supralethal irradiation

    International Nuclear Information System (INIS)

    Timmermans, R.; Gerber, G.B.

    1979-01-01

    The action of biogenic amines (noradrenaline, dopamine), infused at different concentration into the aorta of the urethane anesthetized control and irradiated rats for 2 min., was followed on the basis of systemic blood pressure and mesenteric blood flow. The mesenteric blood flow was measured by means of an electromagnetic flow meter. The changes observed i.e. after dopamine an increase in pressure and flow, after noradrenaline an increase in pressure and a decrease in flow with an increase after infusion had been stopped, correspond to those obtained in larger animals. In many, but not in all cases, the response is proportional to the log of the concentration of the amine infused. Irradiation with 2 kR, i.e. a dose which causes the animals to die from the gastrointestinal syndrome after 3 days modified the response to dopamine and noradrenaline. The changes are, for noradrenaline, a greater pressure and a lower flow responses and for dopamine a greater pressure response at low and middle doses [fr

  11. Blood pressure and mesenteric blood flow in the rat during infusion of biogenic amines. Influence of a supralethal irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Timmermans, R; Gerber, G B [Centre d' Etude de l' Energie Nucleaire, Mol (Belgium)

    1978-01-01

    The action of biogenic amines (noradrenaline, dopamine), infused at different concentration into the aorta of the urethane anesthetized control and irradiated rats for 2 min., was followed on the basis of systemic blood pressure and mesenteric blood flow. The mesenteric blood flow was measured by means of an electromagnetic flow meter. The changes observed i.e. after dopamine an increase in pressure and flow, after noradrenaline an increase in pressure and a decrease in flow with an increase after infusion had been stopped, correspond to those obtained in larger animals. In many, but not in all cases, the response is proportional to the log of the concentration of the amine infused. Irradiation with 2 kR, i.e. a dose which causes the animals to die from the gastrointestinal syndrome after 3 days, modified the response to dopamine and noradrenaline. The changes are, for noradrenaline, a greater pressure and a lower flow responses and for dopamine a greater pressure response at low and middle doses.

  12. CATECHOLAMINES AND β2-ADRENOCEPTOR GENE EXPRESSION BEFORE AND AFTER MAXIMAL INCREMENTAL CYCLE TEST IN YOUNG ICE HOCKEY PLAYERS: RELATION TO WORK PERFORMED

    Directory of Open Access Journals (Sweden)

    Urszula Mazurek

    2013-04-01

    Full Text Available The aim of this study was to assess the plasma adrenaline and noradrenaline concentrations as well as whole blood β2-adrenoceptor gene (ADRB2 expression in young ice hockey players before and immediately after exercise in relation to performed work. Nineteen Youth National Team ice hockey players were subjected to the maximal incremental cycloergometer exercise. The test was done in the pre-competitive phase of training. Among many parameters the plasma adrenaline and noradrenaline concentrations and ADRB2 gene expression in peripheral blood mononuclear cells (PBMC were determined before and after exercise. The average performed work was 3261.3 ± 558.3 J · kg-1 and maximal oxygen consumption (VO2max for all players was 53.85 ± 3.91 mL · kg-1 min-1. The geometric mean of the ADRB2 gene expression was statistically significantly different before and after exercise (P ≤ 0.05, while adrenaline and noradrenaline levels in plasma significantly increased after exercise. In the analysed group of athletes we found that initial level of plasma noradrenaline correlated with the performed work (r = - 0.55, P < 0.014 and normalized ADRB2 expression before the exercise correlated with the work done by them (r = 0.48, P<0.039. However, no statistically significant correlations were found between the plasma adrenaline or noradrenaline concentrations and ADRB2 gene expression in peripheral blood of the players. The performed work in the maximal incremental exercise test of regularly training young ice hockey players depends on the initial levels of noradrenaline in plasma and ADRB2 mRNA in PBMC.

  13. Catecholamines and diabetic autonomic neuropathy

    DEFF Research Database (Denmark)

    Hilsted, J

    1995-01-01

    In diabetic patients with autonomic neuropathy plasma noradrenaline concentration, used as an index of sympathetic nervous activity, is low. This decrease is, however, only found in patients with a long duration of diabetes with clinically severe autonomic neuropathy. This apparent insensitivity...... of plasma catecholamine measurements is not due to changes in the clearance of catecholamines in diabetic autonomic neuropathy. The physiological responses to infused adrenaline and to noradrenaline are enhanced, for noradrenaline mainly cardiovascular responses. Adrenoceptors (alpha and beta adrenoceptors......) are not altered in circulating blood cells in diabetic autonomic neuropathy. Thus, a generalized up-regulation of adrenoceptors does not occur in diabetic autonomic neuropathy....

  14. Prenatal loud music and noise: differential impact on physiological arousal, hippocampal synaptogenesis and spatial behavior in one day-old chicks.

    Science.gov (United States)

    Sanyal, Tania; Kumar, Vivek; Nag, Tapas Chandra; Jain, Suman; Sreenivas, Vishnu; Wadhwa, Shashi

    2013-01-01

    Prenatal auditory stimulation in chicks with species-specific sound and music at 65 dB facilitates spatial orientation and learning and is associated with significant morphological and biochemical changes in the hippocampus and brainstem auditory nuclei. Increased noradrenaline level due to physiological arousal is suggested as a possible mediator for the observed beneficial effects following patterned and rhythmic sound exposure. However, studies regarding the effects of prenatal high decibel sound (110 dB; music and noise) exposure on the plasma noradrenaline level, synaptic protein expression in the hippocampus and spatial behavior of neonatal chicks remained unexplored. Here, we report that high decibel music stimulation moderately increases plasma noradrenaline level and positively modulates spatial orientation, learning and memory of one day-old chicks. In contrast, noise at the same sound pressure level results in excessive increase of plasma noradrenaline level and impairs the spatial behavior. Further, to assess the changes at the molecular level, we have quantified the expression of functional synapse markers: synaptophysin and PSD-95 in the hippocampus. Compared to the controls, both proteins show significantly increased expressions in the music stimulated group but decrease in expressions in the noise group. We propose that the differential increase of plasma noradrenaline level and altered expression of synaptic proteins in the hippocampus are responsible for the observed behavioral consequences following prenatal 110 dB music and noise stimulation.

  15. Prenatal loud music and noise: differential impact on physiological arousal, hippocampal synaptogenesis and spatial behavior in one day-old chicks.

    Directory of Open Access Journals (Sweden)

    Tania Sanyal

    Full Text Available Prenatal auditory stimulation in chicks with species-specific sound and music at 65 dB facilitates spatial orientation and learning and is associated with significant morphological and biochemical changes in the hippocampus and brainstem auditory nuclei. Increased noradrenaline level due to physiological arousal is suggested as a possible mediator for the observed beneficial effects following patterned and rhythmic sound exposure. However, studies regarding the effects of prenatal high decibel sound (110 dB; music and noise exposure on the plasma noradrenaline level, synaptic protein expression in the hippocampus and spatial behavior of neonatal chicks remained unexplored. Here, we report that high decibel music stimulation moderately increases plasma noradrenaline level and positively modulates spatial orientation, learning and memory of one day-old chicks. In contrast, noise at the same sound pressure level results in excessive increase of plasma noradrenaline level and impairs the spatial behavior. Further, to assess the changes at the molecular level, we have quantified the expression of functional synapse markers: synaptophysin and PSD-95 in the hippocampus. Compared to the controls, both proteins show significantly increased expressions in the music stimulated group but decrease in expressions in the noise group. We propose that the differential increase of plasma noradrenaline level and altered expression of synaptic proteins in the hippocampus are responsible for the observed behavioral consequences following prenatal 110 dB music and noise stimulation.

  16. Effects of atomoxetine on attention and impulsivity in the five-choice serial reaction time task in rats with lesions of dorsal noradrenergic ascending bundle.

    Science.gov (United States)

    Liu, Yia-Ping; Huang, Teng-Shun; Tung, Che-Se; Lin, Chen-Cheng

    2015-01-02

    Atomoxetine, a noradrenaline reuptake inhibitor (NRI), which is a non-stimulating medicine that is used for the treatment of patients with attention deficit hyperactivity disorder (ADHD), has been found to be effective in reducing behavioral impulsivity in rodents, but its efficacy in a dorsal noradrenergic ascending bundle (DNAB)-lesioned condition has not been examined. The present study aimed to investigate the effects of DNAB lesions on attention and impulsive control in the five-choice serial reaction time task (5-CSRTT) in rats treated with atomoxetine. The drug-induced changes in noradrenaline efflux in the medial prefrontal cortex were also measured. 5-CSRTT-trained rats were included in one of the following groups: N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4)/Atomoxetine, Sham/Atomoxetine, DSP-4/Saline, or Sham/Saline. Acute atomoxetine (0.3 mg/kg) was administered 14 days after the DSP-4 regime. The behavioral testing included manipulations of the inter-trial interval (ITI), stimulation duration and food satiety. In vivo microdialysis of the noradrenaline efflux in the medial prefrontal cortex and the expression of the noradrenaline transporter (NAT) in the DNAB areas were examined. Atomoxetine reduced impulsivity and perseveration in the long-ITI condition with no effects on any other variables. This phenomenon was not influenced by DSP-4 pre-treatment. The DNAB-lesioned rats had lower noradrenaline efflux in the medial prefrontal cortex. DSP-4 caused no change in NAT expression in the DNAB areas. These findings suggested that noradrenaline reuptake may not be exclusively responsible for the atomoxetine effects in adjusting impulsivity. The role of DNAB should also be considered, particularly in conditions requiring greater behavioral inhibition. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Stimulants and growth in children with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Negrao, Bianca Lee; Viljoen, Margaretha

    2011-07-01

    Initial suggestions that suppression of growth may be an intrinsic characteristic of attention-deficit/hyperactivity disorder (ADHD) have now largely been disproven. Although controversy persists regarding the possible negative effect of adrenergic stimulants on growth in children with ADHD, the consensus that appears to be reached in the scientific literature is that stimulant usage may cause a manageable attenuation of growth in these children. Since it is known that stimulants increase the amount of dopamine and noradrenaline in the synapse, this writing suggests that these increases in dopamine and noradrenaline are responsible for the growth attenuation in these children. It appears that increased amounts of dopamine and noradrenaline have the ability to inhibit the secretion of growth hormone and growth-related hormones such as prolactin, thyroid hormones, sex hormones and insulin. Therefore, it would be reasonable to suggest that the increases in dopamine and noradrenaline caused by stimulant usage can disrupt the homeostasis of both growth hormone and growth-related hormones, generating the potential for the suppression of growth. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. The effects of stress-induced blood components on protein synthesis and secretion in isolated rat hepatocytes

    International Nuclear Information System (INIS)

    Ritchie, A.L.

    1990-01-01

    The effect of stress-induced blood components were examined, specifically adrenaline and noradrenaline, in the presence and absence of rabbit serum or foetal calf serum, on soluble protein synthesis and secretion by isolated hepatocytes maintained in monolayer culture. Rabbit serum and low doses of adrenaline stimulated soluble protein synthesis and secretion whereas foetal calf serum and high doses of noradrenaline were inhibitory. The effect of noradrenaline on soluble protein synthesis and secretion ocurred in the first 12 hours of incubation. The stimulatory effect of adrenaline was still present after 24 hours of incubation. Preloading of the medium with [ 3 H]-leucine i.e. before the addition of sera and/or catecholamines, showed the [ 3 H]-leucine uptake to have occured to a large extent within the first hour of incubation. Noradrenaline supplementation of the medium at two hourly intervals showed no effect on protein synthesis and secretion. The stability of the cetecholamines and the status of the receptors need to be determined for the effective analysis of the results at any point during the incubation. 17 figs., 15 tabs., 83 refs

  19. Stress Alone or associated with Ethanol Induces Prostanoid Release in Rat Aorta via α2-Adrenoceptor

    Energy Technology Data Exchange (ETDEWEB)

    Baptista, Rafaela de Fátima Ferreira [Departamento de Farmacologia - Instituto de Biociências - Universidade Estadual Paulista - UNESP - São Paulo, SP (Brazil); Laboratório de Farmacologia - Faculdade de Medicina de Marília - FAMEMA, SP (Brazil); Taipeiro, Elane de Fátima [Laboratório de Farmacologia - Faculdade de Medicina de Marília - FAMEMA, SP (Brazil); Queiroz, Regina Helena Costa [Departamento de Análise Clínica - Toxicológica e Ciência de Alimentos - Faculdade de Ciências Farmacêuticas - USP, São Paulo, SP (Brazil); Chies, Agnaldo Bruno [Departamento de Farmacologia - Instituto de Biociências - Universidade Estadual Paulista - UNESP - São Paulo, SP (Brazil); Laboratório de Farmacologia - Faculdade de Medicina de Marília - FAMEMA, SP (Brazil); Cordellini, Sandra, E-mail: cordelli@ibb.unesp.br [Departamento de Farmacologia - Instituto de Biociências - Universidade Estadual Paulista - UNESP - São Paulo, SP (Brazil)

    2014-03-15

    Stress and ethanol are both, independently, important cardiovascular risk factors. To evaluate the cardiovascular risk of ethanol consumption and stress exposure, isolated and in association, in male adult rats. Rats were separated into 4 groups: Control, ethanol (20% in drinking water for 6 weeks), stress (immobilization 1h day/5 days a week for 6 weeks) and stress/ethanol. Concentration-responses curves to noradrenaline - in the absence and presence of yohimbine, L-NAME or indomethacin - or to phenylephrine were determined in thoracic aortas with and without endothelium. EC50 and maximum response (n=8-12) were compared using two-way ANOVA/Bonferroni method. Either stress or stress in association with ethanol consumption increased the noradrenaline maximum responses in intact aortas. This hyper-reactivity was eliminated by endothelium removal or by the presence of either indomethacin or yohimbine, but was not altered by the presence of L-NAME. Meanwhile, ethanol consumption did not alter the reactivity to noradrenaline. The phenylephrine responses in aortas both with and without endothelium also remained unaffected regardless of protocol. Chronic stress increased rat aortic responses to noradrenaline. This effect is dependent upon the vascular endothelium and involves the release of vasoconstrictor prostanoids via stimulation of endothelial alpha-2 adrenoceptors. Moreover, chronic ethanol consumption appeared to neither influence noradrenaline responses in rat thoracic aorta, nor did it modify the increase of such responses observed as a consequence of stress exposure.

  20. Stress Alone or associated with Ethanol Induces Prostanoid Release in Rat Aorta via α2-Adrenoceptor

    International Nuclear Information System (INIS)

    Baptista, Rafaela de Fátima Ferreira; Taipeiro, Elane de Fátima; Queiroz, Regina Helena Costa; Chies, Agnaldo Bruno; Cordellini, Sandra

    2014-01-01

    Stress and ethanol are both, independently, important cardiovascular risk factors. To evaluate the cardiovascular risk of ethanol consumption and stress exposure, isolated and in association, in male adult rats. Rats were separated into 4 groups: Control, ethanol (20% in drinking water for 6 weeks), stress (immobilization 1h day/5 days a week for 6 weeks) and stress/ethanol. Concentration-responses curves to noradrenaline - in the absence and presence of yohimbine, L-NAME or indomethacin - or to phenylephrine were determined in thoracic aortas with and without endothelium. EC50 and maximum response (n=8-12) were compared using two-way ANOVA/Bonferroni method. Either stress or stress in association with ethanol consumption increased the noradrenaline maximum responses in intact aortas. This hyper-reactivity was eliminated by endothelium removal or by the presence of either indomethacin or yohimbine, but was not altered by the presence of L-NAME. Meanwhile, ethanol consumption did not alter the reactivity to noradrenaline. The phenylephrine responses in aortas both with and without endothelium also remained unaffected regardless of protocol. Chronic stress increased rat aortic responses to noradrenaline. This effect is dependent upon the vascular endothelium and involves the release of vasoconstrictor prostanoids via stimulation of endothelial alpha-2 adrenoceptors. Moreover, chronic ethanol consumption appeared to neither influence noradrenaline responses in rat thoracic aorta, nor did it modify the increase of such responses observed as a consequence of stress exposure

  1. Mucuna pruriens improves male fertility by its action on the hypothalamus-pituitary-gonadal axis.

    Science.gov (United States)

    Shukla, Kamla Kant; Mahdi, Abbas Ali; Ahmad, Mohammad Kaleem; Shankhwar, Satya Narain; Rajender, Singh; Jaiswar, Shyam Pyari

    2009-12-01

    To understand the mechanism of action of Mucuna pruriens in the treatment of male infertility. Prospective study. Departments of Biochemistry, Urology, and Obstetrics and Gynecology, C.S.M. Medical University, Lucknow, India. Seventy-five normal healthy fertile men (controls) and 75 men undergoing infertility screening. High-performance liquid chromatography assay for quantitation of dopa, adrenaline, and noradrenaline in seminal plasma and blood. Estimation by RIA of hormonal parameters in blood plasma, namely T, LH, FSH, and PRL. Before and after treatment, serum T, LH, FSH, PRL, dopamine, adrenaline, and noradrenaline in seminal and blood plasma were measured. Decreased sperm count and motility were seen in infertile subjects. Serum T and LH levels, as well as seminal plasma and blood levels of dopamine, adrenaline, and noradrenaline were also decreased in all groups of infertile men. This was accompanied by significantly increased serum FSH and PRL levels in oligozoospermic subjects. Treatment with M. pruriens significantly improved T, LH, dopamine, adrenaline, and noradrenaline levels in infertile men and reduced levels of FSH and PRL. Sperm count and motility were significantly recovered in infertile men after treatment. Treatment with M. pruriens regulates steroidogenesis and improves semen quality in infertile men.

  2. Influence of acute treatment with sibutramine on the sympathetic neurotransmission of the young rat vas deferens.

    Science.gov (United States)

    de Souza, Bruno Palmieri; da Silva, Edilson Dantas; Jurkiewicz, Aron; Jurkiewicz, Neide Hyppolito

    2014-09-05

    The effects of acute treatment with sibutramine on the peripheral sympathetic neurotransmission in vas deferens of young rats were still not evaluated. Therefore, we carried out this study in order to verify the effects of acute sibutramine treatment on the neuronal- and exogenous agonist-induced contractions of the young rat vas deferens. Young 45-day-old male Wistar rats were pretreated with sibutramine 6 mg/kg and after 4h the vas deferens was used for experiment. The acute treatment with sibutramine was able to increase the potency (pD2) of noradrenaline and phenylephrine. Moreover, the efficacy (Emax) of noradrenaline was increased while the efficacy of serotonin and nicotine were decreased. The maximum effect induced by a single concentration of tyramine was diminished in the vas deferens from treated group. Moreover, the leftward shift of the noradrenaline curves promoted by uptake blockers (cocaine and corticosterone) and β-adrenoceptor antagonist (propranolol) was reduced in the vas deferens of treated group. The initial phasic and secondary tonic components of the neuronal-evoked contractions of vas deferens from treated group at the frequencies of 2 Hz were decreased. Moreover, only the initial phasic component at 5 Hz was diminished by the acute treatment with sibutramine. In conclusion, we showed that the acute treatment with sibutramine in young rats was able to affect the peripheral sympathetic nervous system by inhibition of noradrenaline uptake and reduction of the neuronal content of this neurotransmitter, leading to an enhancement of vas deferens sensitivity to noradrenaline. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Catecholamines promote the expression of virulence and oxidative stress genes in Porphyromonas gingivalis.

    Science.gov (United States)

    Graziano, T S; Closs, P; Poppi, T; Franco, G C; Cortelli, J R; Groppo, F C; Cogo, K

    2014-10-01

    Stress has been identified as an important risk factor in the development of many infectious diseases, including periodontitis. Porphyromonas gingivalis, a gram-negative oral anaerobic bacterium, is considered an important pathogen in chronic periodontitis. Microorganisms, including P. gingivalis, that participate in infectious diseases have been shown to respond to catecholamines released during stress processes by modifying their growth and virulence. Therefore, the purpose of this study was to evaluate the effects of adrenaline and noradrenaline on the growth, antimicrobial susceptibility and gene expression in P. gingivalis. P. gingivalis was incubated in the presence of adrenaline and noradrenaline (100 μm) for different time-periods in rich (Tryptic soy broth supplemented with 0.2% yeast extract, 5 μg/mL of hemin and 1 μg/mL of menadione) and poor (serum-SAPI minimal medium and serum-SAPI minimal medium supplemented with 5 μg/mL of hemin and 1 μg/mL of menadione) media, and growth was evaluated based on absorbance at 660 nm. Bacterial susceptibility to metronidazole was examined after exposure to adrenaline and noradrenaline. The expression of genes involved in iron acquisition, stress oxidative protection and virulence were also evaluated using RT-quantitative PCR. Catecholamines did not interfere with the growth of P. gingivalis, regardless of nutritional or hemin conditions. In addition, bacterial susceptibility to metronidazole was not modified by exposure to adrenaline or noradrenaline. However, the expression of genes related to iron acquisition (hmuR), oxidative stress (tpx, oxyR, dps, sodB and aphC) and pathogenesis (hem, hagA and ragA) were stimulated upon exposure to adrenaline and/or noradrenaline. Adrenaline and noradrenaline can induce changes in gene expression related to oxidative stress and virulence factors in P. gingivalis. The present study is, in part, a step toward understanding the stress-pathogen interactions that may

  4. Effects of minoxidil and nitroprusside on reflex increases in myocardial contractility.

    Science.gov (United States)

    Robie, N W

    1978-01-01

    1 The effects of nitroprusside and minoxidil on increases in myocardial contractility resulting from carotid artery occlusion were investigated in anaesthetized dogs. The results were compared with those produced by intravenous influsion of noradrenaline. 2 Nitroprusside and minoxidil attenuated the pressor responses produced by carotid artery occlusion. 3 Nitroprusside, but not minoxidil, attenuated the maximal myocardial contractility resulting from carotid occlusion. 4 The pressor and contractility responses to noradrenaline infusion were unaffected by either agent. 5 Nitroprusside failed to alter the myocardial responses produced by dimethylphenylpiperazinium. 6 These results, in conjunction with those of other investigators who have demonstrated that nitroprusside does not affect the release of noradrenaline from adrenergic neurons, suggest that nitroprusside may inhibit sympathetic nervous system reflex activity via an afferent and/or central component. PMID:620094

  5. The celiac ganglion modulates LH-induced inhibition of androstenedione release in late pregnant rat ovaries

    Directory of Open Access Journals (Sweden)

    Rastrilla Ana M

    2006-12-01

    Full Text Available Abstract Background Although the control of ovarian production of steroid hormones is mainly of endocrine nature, there is increasing evidence that the nervous system also influences ovarian steroidogenic output. The purpose of this work was to study whether the celiac ganglion modulates, via the superior ovarian nerve, the anti-steroidogenic effect of LH in the rat ovary. Using mid- and late-pregnant rats, we set up to study: 1 the influence of the noradrenergic stimulation of the celiac ganglion on the ovarian production of the luteotropic hormone androstenedione; 2 the modulatory effect of noradrenaline at the celiac ganglion on the anti-steroidogenic effect of LH in the ovary; and 3 the involvement of catecholaminergic neurotransmitters released in the ovary upon the combination of noradrenergic stimulation of the celiac ganglion and LH treatment of the ovary. Methods The ex vivo celiac ganglion-superior ovarian nerve-ovary integrated system was used. This model allows studying in vitro how direct neural connections from the celiac ganglion regulate ovarian steroidogenic output. The system was incubated in buffer solution with the ganglion and the ovary located in different compartments and linked by the superior ovarian nerve. Three experiments were designed with the addition of: 1 noradrenaline in the ganglion compartment; 2 LH in the ovarian compartment; and 3 noradrenaline and LH in the ganglion and ovarian compartments, respectively. Rats of 15, 19, 20 and 21 days of pregnancy were used, and, as an end point, the concentration of the luteotropic hormone androstenedione was measured in the ovarian compartment by RIA at various times of incubation. For some of the experimental paradigms the concentration of various catecholamines (dihydroxyphenylalanine, dopamine, noradrenaline and adrenaline was also measured in the ovarian compartment by HPLC. Results The most relevant result concerning the action of noradrenaline in the celiac ganglion

  6. Radioprotective effect of catecholamines on the cultured Chinese hamster fibroblasts

    International Nuclear Information System (INIS)

    Chirkov, Yu.Yu.; Malatsidze, M.A.; Sobolev, A.S.

    1985-01-01

    On cultivated in vitro Chinese hamster fibroblasts radioprotective properties of adrenaline, noradrenaline and isoproterenol in different concentrations are studied. Isoproterenol radiopreventive effect is clearly manifested with its concentration being 1x10 -8 M; adrenaline and noradrenaline are efficient in higher concentrations. Propranolol, blocking β-adrenergic receptors, completely presents radioprotective effect of catecholamines on the cells. β-adrenergic mechanism of catecholamine radioprotective effect on Mammalia cells is discussed

  7. [(35)S]-GTPgammaS autoradiography reveals alpha(2) adrenoceptor-mediated G-protein activation in amygdala and lateral septum.

    Science.gov (United States)

    Newman-Tancredi, A; Chaput, C; Touzard, M; Millan, M J

    2000-04-03

    alpha(2)-adrenoceptor-mediated G-protein activation was examined by [(35)S]-GTPgammaS autoradiography. In alpha(2)-adrenoceptor-rich regions (amygdala, lateral septum), noradrenaline stimulated [(35)S]-GTPgammaS binding. These actions were abolished by the selective alpha(2) antagonist, atipamezole. Conversely, in caudate nucleus, which expresses few alpha(2) receptors, noradrenaline-induced stimulation was not inhibited by atipamezole, suggesting that it is not mediated by alpha(2)-adrenoceptors.

  8. Splanchnic and renal elimination and release of catecholamines in cirrhosis. Evidence of enhanced sympathetic nervous activity in patients with decompensated cirrhosis

    DEFF Research Database (Denmark)

    Ring-Larsen, H; Kanstrup, I L; Christensen, N J

    1984-01-01

    Plasma noradrenaline (NA) and adrenaline (A) concentrations were determined in different vascular areas in 32 patients with cirrhosis and in nine controls during a right sided heart, liver, and renal vein catheterisation. The patients were divided into four groups: (I) Compensated (without ascites......, respectively, the three last mentioned values being significantly raised (p less than 0.01). Median arterial adrenaline concentrations were not significantly increased. In patients arterial-hepatic venous extraction ratios of noradrenaline and adrenaline were on the average 25% (p less than 0.01) and 20% (p...... differences were significantly increased in groups II, III and IV (0.47, 0.53 and 0.68 nmol/l, p less than 0.01), indicating a significant net release of noradrenaline from the kidneys in recompensated and decompensated patients. Renal extraction of adrenaline was normal. In conclusion, increased arterial...

  9. Plasma catecholamine level and portal venous pressure as guides to prognosis in patients with cirrhosis

    DEFF Research Database (Denmark)

    Tage-Jensen, U; Henriksen, Jens Henrik; Christensen, E

    1988-01-01

    clinical and biochemical variables and survival. Forty-seven (58%) of the patients died during the follow-up period. Univariate analysis showed that plasma noradrenaline and adrenaline concentrations, portal pressure, indocyanine green clearance, serum sodium, bilirubin, and albumin concentrations......, and the presence of ascites or cardiovascular disease were of significant prognostic value. In a multivariate analysis (Cox regression model), plasma noradrenaline concentration, portal pressure, serum bilirubin concentration, and the presence of ascites and cardiovascular disease remained significant independent...

  10. Comparison of the effects of sibutramine and other monoamine reuptake inhibitors on food intake in the rat

    Science.gov (United States)

    Jackson, Helen C; Needham, Andrew M; Hutchins, Lisa J; Mazurkiewicz, Sarah E; Heal, David J

    1997-01-01

    The effects of the potent 5-hydroxytryptamine (5-HT) and noradrenaline reuptake inhibitor (serotonin-noradrenaline reuptake inhibitor, SNRI), sibutramine, on the cumulative food intake of freely-feeding male Sprague-Dawley rats during an 8 h dark period were investigated and compared to those of the selective 5-HT reuptake inhibitor (selective serotonin reuptake inhibitor, SSRI), fluoxetine; the selective noradrenaline reuptake inhibitor, nisoxetine; the 5-HT and noradrenaline reuptake inhibitors, venlafaxine and duloxetine; and the 5-HT releaser and 5-HT reuptake inhibitor, (+)-fenfluramine. Sibutramine (3 and 10 mg kg−1, p.o.) and (+)-fenfluramine (1 and 3 mg kg−1, p.o.) produced a significant, dose-dependent decrease in food intake over the 8 h dark period. These responses became apparent within the first 2 h following drug administration. Fluoxetine (3, 10 and 30 mg kg−1, p.o.), and nisoxetine (3, 10 and 30 mg kg−1, p.o.) had no significant effect on food intake during the 8 h dark period. However, a combination of fluoxetine and nisoxetine (30 mg kg−1, p.o., of each) significantly decreased food intake 2 and 8 h after drug administration. Venlafaxine (100 and 300 mg kg−1, p.o.) and duloxetine (30 mg kg−1, p.o.) also significantly decreased food intake in the 2 and 8 h following drug administration. The results of this study demonstrate that inhibition of 5-HT and noradrenaline reuptake by sibutramine, venlafaxine, duloxetine, or by a combination of fluoxetine and nisoxetine, markedly reduces food intake in freely-feeding rats and suggest that this may be a novel approach for the treatment of obesity. PMID:9283714

  11. Mean 24-hours sympathetic nervous system activity decreases during head-down tilted bed rest but not during microgravity

    Science.gov (United States)

    Christensen, Nj; Heer, M.; Ivanova, K.; Norsk, P.

    Sympathetic nervous system activity is closely related to gravitational stress in ground based experiments. Thus a high activity is present in the standing-up position and a very low activity is observed during acute head-out water immersion. Adjustments in sympathetic activity are necessary to maintain a constant blood pressure during variations in venous return. Head-down tilted bed rest is applied as a model to simulate changes observed during microgravity. The aim of the present study was to test the hypothesis that mean 24-hours sympathetic activity was low and similar during space flight and in ground based observation obtained during long-term head-down tilted bed rest. Forearm venous plasma noradrenaline was measured by a radioenzymatic technique as an index of muscle sympathetic activity and thrombocyte noradrenaline and adrenaline were measured as indices of mean 24-hours sympathoadrenal activity. Previous results have indicated that thrombocyte noradrenaline level has a half-time of 2 days. Thus to reflect sympathetic activity during a specific experiment the study period must last for at least 6 days and a sample must be obtained within 12 hours after the experiment has ended. Ten normal healthy subjects were studied before and during a 14 days head-down tilted bed rest as well as during an ambulatory study period of a similar length. The whole experiment was repeated while the subjects were on a low calorie diet. Thrombocyte noradrenaline levels were studied in 4 cosmonauts before and within 12 hours after landing after more than 7 days in flight. Thrombocyte noradrenaline decreased markedly during the head-down tilted bed rest (pdifferent in cosmonauts and in subjects participating in the head down tilted bed rest study (170± 29% (Mean± SEM) vs. 57± 7%, respectively; presponse to combined effects of a reduced plasma volume and an increased vascular capacity in flight.

  12. Regulation of eye and jaw colouration in three-spined stickleback Gasterosteus aculeatus.

    Science.gov (United States)

    Franco-Belussi, L; De Oliveira, C; Sköld, H N

    2018-03-25

    Fish can change their skin and eye colour for background matching and signalling. Males of Gasterosteus aculeatus develop ornamental blue eyes and a red jaw during the reproductive season, colours that are further enhanced during courtship. Here, the effects of different hormones on physiological colour changes in the eyes and jaws of male and female G. aculeatus were investigated in vitro. In an in vivo experiment, G. aculeatus were injected with a receptor blocker of a pivotal hormone (noradrenaline) that controls colour change. In males, noradrenaline had aggregating effects on melanophore and erythrophore pigments resulting in blue eyes and a pale jaw, whereas melanocyte-concentrating hormone (MCH) and melatonin resulted in a pale jaw only. When noradrenalin was combined with melanocyte stimulating hormone (MSH) or prolactin, the jaw became red, while the eyes remained blue. In vivo injection of yohimbine, an alpha-2 adrenoreceptor blocker, resulted in dispersion of melanophore pigment in the eyes and inhibited the blue colouration. Altogether, the data suggest that noradrenalin has a pivotal role in the short-term enhancement of the ornamental colouration of male G. aculeatus, potentially together with MSH or prolactin. This study also found a sex difference in the response to MCH, prolactin and melatonin, which may result from different appearance strategies in males, versus the more cryptic females. © 2018 The Fisheries Society of the British Isles.

  13. Noradrenaline or terlipressin for hepatorenal syndrome?

    Directory of Open Access Journals (Sweden)

    Pilar Celis

    2015-08-01

    Full Text Available El síndrome hepatorrenal es una condición asociada a altísima mortalidad, que puede ser recuperada en ciertos casos con el uso de vasoconstrictores. Generalmente se considera que terlipresina es el tratamiento estándar, pero noradrenalina se ha planteado como una alternativa. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos seis revisiones sistemáticas que en conjunto incluyen cuatro estudios aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que noradrenalina y terlipresina son probablemente igual de efectivas en lograr mejoría del síndrome hepatorrenal y disminuir la mortalidad, pero que noradrenalina se asocia a menos efectos adversos, y tiene un menor costo.

  14. Noradrenalin a chování

    Czech Academy of Sciences Publication Activity Database

    Prokopová, Iva

    2010-01-01

    Roč. 59, č. 2 (2010), s. 51-58 ISSN 1210-6313 R&D Projects: GA ČR(CZ) GA309/09/0286; GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : norepinephrine * learning * memory Subject RIV: FH - Neurology

  15. Catecholamine responses to changes in posture during human pregnancy.

    Science.gov (United States)

    Whittaker, P G; Gerrard, J; Lind, T

    1985-06-01

    Human pregnancy may induce changes in the sensitivity of the cardiovascular system to endogenous catecholamines. This was investigated in multigravid women with little likelihood of unsuspected vascular disease. The responses of blood pressure, pulse rate, plasma noradrenaline and adrenaline to a change in posture from semi-recumbency to standing were assessed in six normotensive women at 36 weeks gestation and in six non-pregnant control subjects. Standing for 10 min caused a surge in blood pressure, pulse rate and plasma noradrenaline in non-pregnant women. The pregnant women, whose basal levels of noradrenaline were higher than those in non-pregnant women, showed a slower noradrenergic response to postural change, and this response had less effect upon the cardiovascular indices. Blood pressure dropped immediately on standing and pulse rate remained unaffected throughout. It is suggested that some women may maintain a non-pregnant level of pressor sensitivity during pregnancy and thereby become hypertensive.

  16. Distribution of catecholamines and serotonin in the rat cerebral cortex:

    International Nuclear Information System (INIS)

    Reader, T.A.

    1981-01-01

    The rat cerebral cortex was dissected in five regions and analyzed for the catecholamines noradrenaline, adrenaline and dopamine, and for the indoleamine seroton in using sensitive radioenzymatic assay methods with thin-layer-chromatography. The noradrenaline concentration was highest in the ventral cortex, lateral to the hypothalamus, had intermediate values for the prefrontal, frontal and parietal cortical areas and was lowest in the occipital cortex. Dopamine levels were also highest in the cortex lateral to the hypothalamus, and moderate in the prefrontal and frontal cortical areas, with the lowest values measured for the occipital cortex. The ratios dopamine/noradrenaline further support the hypothesis that they are independent transmitters. Traces of adrenaline were measured in all regions examined. The serotonin distribution was found to be non-homogeneous, with the highest values for the prefrontal cortex and ventral cortex lateral to the hypothalamus. The functional significance of these amines and their ratios are discussed in relation to their role as putative modulators of cortical neuronal excitability. (author)

  17. On the regulatory functions of neuropeptide Y (NPY) with respect to vascular resistance and exocrine and endocrine secretion in the pig pancreas

    DEFF Research Database (Denmark)

    Holst, J J; Orskov, C; Knuhtsen, S

    1989-01-01

    We compared the effects of electrical stimulation of the splanchnic nerves and infusions of neuropeptide Y, noradrenaline or a combination of the two on pancreatic vascular resistance and exocrine and endocrine secretion. For these studies we used isolated perfused pig pancreas with preserved...... splanchnic nerve supply. The exocrine secretion was stimulated with physiological concentrations of secretin and cholecystokinin octapeptide. Noradrenaline and NPY at 10(-8) M both increased pancreatic perfusion pressure. Their effects were additive and similar in magnitude to that of electrical stimulation...

  18. Temporal responses of cutaneous blood flow and plasma catecholamine concentrations to histamine H1- or H2-receptor stimulation in man

    DEFF Research Database (Denmark)

    Knigge, U; Alsbjørn, B; Thuesen, B

    1988-01-01

    continuously with a laser Doppler flowmeter, and noradrenaline and adrenaline concentrations were determined in blood samples drawn every 15 min. The infusion of histamine caused an immediate and sustained vasodilatation. The Concomitant infusion of mepyramine prevented the immediate vasodilatation, but had...... noradrenaline, while the increase during concomitant H1-receptor blockade was delayed but achieved the level observed during the histamine infusion. The response to histamine during H2-receptor blockade was small and transient. The rise in plasma adrenaline was not significant. These findings suggest...

  19. Objawy naczynioruchowe w menopauzie – diagnostyka i leczenie

    Directory of Open Access Journals (Sweden)

    Małgorzata Sobstyl

    2011-06-01

    Full Text Available Hot flashes and night sweats are common menopausal symptoms, which influence greatly the quality of women’s lives, often by eliminating them from professional or everyday lives. Etiopathogenesis of symptoms has not been fully explained. A great role is attributed to sudden decrease of estrogens, disorders of neurotransmitters and neuromodulators activity such as noradrenalin, dopamine, serotonin and thermoregulation disorders. Estrogen and estrogen-progestogen therapy is recommended as the most effective treatment for vasomotor symptoms. Yet, more and more consideration should be given to selective inhibitors of serotonin and noradrenalin, gabapentin.

  20. Adrenergic receptors inhibit TRPV1 activity in the dorsal root ganglion neurons of rats.

    Science.gov (United States)

    Matsushita, Yumi; Manabe, Miki; Kitamura, Naoki; Shibuya, Izumi

    2018-01-01

    Transient receptor potential vanilloid type 1 (TRPV1) is a polymodal receptor channel that responds to multiple types of stimuli, such as heat, acid, mechanical pressure and some vanilloids. Capsaicin is the most commonly used vanilloid to stimulate TRPV1. TRPV1 channels are expressed in dorsal root ganglion neurons that extend to Aδ- and C-fibers and have a role in the transduction of noxious inputs to the skin into the electrical signals of the sensory nerve. Although noradrenergic nervous systems, including the descending antinociceptive system and the sympathetic nervous system, are known to modulate pain sensation, the functional association between TRPV1 and noradrenaline in primary sensory neurons has rarely been examined. In the present study, we examined the effects of noradrenaline on capsaicin-evoked currents in cultured dorsal root ganglion neurons of the rat by the whole-cell voltage clamp method. Noradrenaline at concentrations higher than 0.1 pM significantly reduced the amplitudes of the inward capsaicin currents recorded at -60 mV holding potential. This inhibitory action was reversed by either yohimbine (an α2 antagonist, 10 nM) or propranolol (a β antagonist, 10 nM). The α2 agonists, clonidine (1 pM) and dexmedetomidine (1 pM) inhibited capsaicin currents, and yohimbine (1 nM) reversed the effects of clonidine. The inhibitory action of noradrenaline was not seen in the neurons pretreated with pertussis toxin (100 μg/ml for 24 h) and the neurons dialyzed intracellularly with guanosine 5'- [β-thio] diphosphate (GDPβS, 200 μM), the catalytic subunit of protein kinase A (250 U/ml) or okadaic acid (1 μM). These results suggest that noradrenaline directly acts on dorsal root ganglion neurons to inhibit the activity of TRPV1 depending on the activation of α2-adrenoceptors followed by the inhibition of the adenylate cyclase/cAMP/protein kinase A pathway.

  1. Vasodilatation with pinacidil. Mode of action in rat resistance vessels

    International Nuclear Information System (INIS)

    Videbaek, L.M.; Aalkjaer, C.; Mulvany, M.J.

    1988-01-01

    Pinacidil is a newly developed antihypertensive vasodilator, proposed to belong to the new group of smooth muscle relaxants, the K+ channel openers. The in vitro effects of pinacidil on induced tone, smooth muscle membrane potential and 86 Rb and 42 K efflux from rat resistance vessels (internal diameter about 200 microns) were studied. Tone induced with noradrenaline was concentration-dependently inhibited by pinacidil. Responses to electrical field stimulation were also inhibited. However, tone induced with high K+ depolarization, noradrenaline in the presence of high K+, caffeine-induced contractions and noradrenaline contractions in the presence of felodipine were little affected by pinacidil. Pinacidil caused concentration-dependent hyperpolarisation of the resting smooth muscle. Pinacidil caused only a small and transient increase of the 86 Rb efflux rate constant, while the same concentrations of pinacidil produced a significant increase in the 42 K efflux rate constant. Our results seem to indicate that the relaxant effect of pinacidil is the result of an increase in K+ permeability, thus causing hyperpolarisation and relaxation. The opened K+ channels appear to be selective for K+ over Rb+

  2. Need for beta-blockade in hypertension reduced with long-term minoxidil.

    Science.gov (United States)

    Brunner, H R; Jaeger, P; Ferguson, R K; Jequier, E; Turini, G; Gavras, H

    1978-01-01

    Sequential changes in plasma renin activity and urinary aldosterone and noradrenaline were assessed in eight patients with severe hypertension after minoxidil had been added to their treatment. Doses of 2.5--27.5 (mean 12.5) mg/day reduced the mean blood pressure from 166/113 +/-6/2 mm Hg to 124/88+/-4/2 mm Hg in one week. Plasma renin activity and urinary aldosterone and noradrenaline increased twofold to threefold initially but returned to baseline values within two to three weeks and remained unchanged during a mean follow-up of 5.1 months. Beta-blocking drugs were then withdrawn slowly in six patients without adverse effects, though blood pressure and heart rate increased in three patients, who required minimal doses of beta-blockers. Plasma renin activity and urinary aldosterone and noradrenaline did not change significantly after beta-blockade had been stopped. We conclude that the need for beta-blockade is greatly reduced with long-term minoxidil treatment and that it may be unnecessary in some patients. PMID:28811

  3. Potentiometric and NMR complexation studies of phenylboronic acid PBA and its aminophosphonate analog with selected catecholamines

    Science.gov (United States)

    Ptak, Tomasz; Młynarz, Piotr; Dobosz, Agnieszka; Rydzewska, Agata; Prokopowicz, Monika

    2013-05-01

    Boronic acids are a class of intensively explored compounds, which according to their specific properties have been intensively explored in last decades. Among them phenylboronic acids and their derivatives are most frequently examined as receptors for diverse carbohydrates. In turn, there is a large gap in basic research concerning complexation of catecholamines by these compounds. Therefore, we decided to undertake studies on interaction of chosen catecholamines, namely: noradrenaline (norephinephrine), dopamine, L-DOPA, DOPA-P (phosphonic analog of L-DOPA) and catechol, with simple phenyl boronic acid PBA by means of potentiometry and NMR spectroscopy. For comparison, the binding properties of recently synthesized phenylboronic receptor 1 bearing aminophosphonate function in meta-position were investigated and showed promising ability to bind catecholamines. The protonation and stability constants of PBA and receptor 1 complexes were examined by potentiometry. The obtained results demonstrated that PBA binds the catecholamines with the following affinity order: noradrenaline ⩾ dopamine ≈ L-DOPA > catechol > DOPA-P, while its modified analog 1 reveals slightly different preferences: dopamine > noradrenaline > catechol > L-DOPA > DOPA-P.

  4. [Biogenic amines in the epiphysis and hypothalamus under normal conditions and following ovariectomy].

    Science.gov (United States)

    Grishchenko, V I; Koliada, L D; Demidenko, D I

    1977-01-01

    Melatonin content in the epiphysis, serotonin, noradrenaline, dopamine-in the hypothalamus, gonadotropins--in the hypophysis of rats was studied under normal conditions and following ovariectomy; regularly of the estral cycle phases was studied as well. Two series of experiments were conducted on 120 rats with regular estral cycles. The animals were divided into groups according to the estral cycle phase. Melatonin concentration in the epiphysis, serotonin, noradrenaline, dopamine--in the hypothalamus was subject to variations coinciding with the estral cycle phases. Serotonin, noradrenaline, and dopamine content decreased in the hypophysis of ovariectomized rats in comparison with control; melatonin content rose in the epiphysis. There was no complete extinction of the estral cycle in the course of investigation (20 days). The action of castration on the sexual cycle depended on the phase at which the rats were subjected to ovariectomy. A reverse relationship existed between the melatonin content in the epiphysis and serotonin content in the hypothalamus, this serving as one of the important factors in the regulation of the sexual function.

  5. The costo-uterine muscle of the rat contains a homogeneous population of beta-adrenoceptors.

    Science.gov (United States)

    Hartley, M. L.; Pennefather, J. N.

    1985-01-01

    The effects of two selective beta-adrenoceptor antagonists on the inhibitory responses to some sympathomimetic amines of electrically-stimulated preparations of costo-uterine muscle, taken from virgin rats, have been examined quantitatively. pA2 values for the antagonist, atenolol (beta 1-selective) and ICI 118,551 (beta 2-selective) were obtained using as agonists, fenoterol (beta 2-selective agonist) and noradrenaline (alpha- and beta-adrenoceptor agonist, beta 1-selective); and in addition, with ICI 118,551 only, isoprenaline (beta-agonist, non-selective) and adrenaline (alpha- and beta-adrenoceptor agonist, beta 2-selective). Catecholamine uptake mechanisms and alpha-adrenoceptors were not blocked in any of these experiments. Atenolol competitively antagonized the effects of fenoterol and noradrenaline to a similar extent, the pA2 values being 5.4 and 5.7, respectively. ICI 118,551 competitively antagonized the effects of fenoterol, isoprenaline, adrenaline and noradrenaline to a similar extent; pA2 values ranged from 8.7 with noradrenaline to 9.1 with isoprenaline. These results extend our previous observations which indicated that the adrenoceptors mediating inhibition of electrically-evoked contractions of costo-uterine muscle of the virgin rat are homogeneous and of the beta 2-subtype. The potency of the beta 1-selective agonist RO 363 in producing inhibition of electrically-evoked contractions of this tissue was also examined. RO 363 was 200 times less potent than isoprenaline but was a full agonist. This indicates that there is efficient coupling between beta 2-adrenoceptor activation and tissue response in this non-innervated preparation. PMID:2858239

  6. Effects of nifedipine on anorectal smooth muscle in vitro.

    Science.gov (United States)

    Cook, T A; Brading, A F; Mortensen, N J

    1999-06-01

    Glyceryl trinitrate reduces anal resting pressure and aids the healing of anal fissures. However, some patients develop tachyphylaxis and the fissure fails to heal, suggesting that other agents are needed. This study assesses the effects of nifedipine (a calcium channel antagonist) in modulating resting tone and agonist-induced contractions in human internal anal sphincter (IAS) and rectal circular muscle. Smooth muscle strips from the IAS and rectal circular muscle from ten patients undergoing surgical resection were mounted for isometric tension recording in a superfusion organ bath. The effects of noradrenaline and carbachol were assessed in the presence of various perfusates. LAS strips developed tone and spontaneous activity. Noradrenaline produced dose-dependent contractions. In calcium-free Krebs solution, tone and activity were abolished and no contractions were elicited in response to noradrenaline. Nifedipine also abolished tone and spontaneous activity, but contractions to noradrenaline were only slightly attenuated. In contrast, rectal smooth muscle strips developed spontaneous activity but no resting tone and contracted in response to carbachol. In calcium-free Krebs solution, the spontaneous activity and carbachol contractions were abolished. Addition of nifedipine to the perfusate abolished spontaneous activity and greatly reduced contractions. These data suggest that spontaneous activity and resting tone are dependent on extracellular calcium and flux across the cells. Agonist-induced contraction in the IAS is attributable mainly to the release of calcium from intracellular stores, whereas rectal circular smooth muscle depends principally on extracellular calcium entering the cell for contraction. The attenuation of contractions in both tissues and the abolition of resting tone in the IAS suggest that nifedipine may be useful in the management of patients with anorectal disorders.

  7. Role for astroglial α1-adrenoreceptors in gliotransmission and control of synaptic plasticity in the neocortex

    Directory of Open Access Journals (Sweden)

    Yuriy ePankratov

    2015-06-01

    Full Text Available Communication between neuronal and glial cells is thought to be very important for many brain functions. Acting via release of gliotransmitters, astrocytes can modulate synaptic strength. The mechanisms underlying gliotransmission remain uncertain with exocytosis being the most intriguing and debated pathway.We demonstrate that astroglial α1-adrenoreceptors are very sensitive to noradrenaline and make a significant contribution to intracellular Ca2+-signalling in layer 2/3 neocortical astrocytes. We also show that astroglial α1-adrenoreceptors are prone to desensitization upon prolonged exposure to noradrenaline.We show that within neocortical slices, α-1adrenoreceptors can activate vesicular release of ATP and D-serine from cortical astrocytes which initiate a burst of ATP receptor-mediated currents in adjacent pyramidal neurons. These purinergic currents can be inhibited by intracellular perfusion of astrocytes with Tetanus Toxin light chain, verifying their origin via astroglial exocytosis.We show that α1 adrenoreceptor-activated release of gliotransmitters is important for the induction of synaptic plasticity in the neocortex:long-term potentiation (LTP of neocortical excitatory synaptic potentials can be abolished by the selective α1-adrenoreceptor antagonist terazosin. We show that weak sub-threshold theta-burst stimulation can induce LTP when astrocytes are additionally activated by 1 μM noradrenaline. This facilitation is dependent on the activation of neuronal ATP receptors and is abolished in neocortical slices from dn-SNARE mice which have impaired glial exocytosis. Importantly, facilitation of LTP by noradrenaline can be significantly reduced by perfusion of individual astrocytes with Tetanus Toxin. Our results strongly support the physiological importance of astroglial adrenergic signalling and exocytosis of gliotransmitters for modulation of synaptic transmission and plasticity .

  8. Laminar pattern of cholinergic and adrenergic receptors in rat visual cortex using quantitative receptor autoradiography

    International Nuclear Information System (INIS)

    Schliebs, R.; Walch, C.

    1989-01-01

    The laminar distribution of muscarinic acetylcholine receptors, including the M1-receptor subtype, of beta-adrenergic receptors, and noradrenaline uptake sites, was studied in the adult rat visual, frontal, somatosensory and motor cortex, using quantitative receptor autoradiography. In the visual cortex, the highest density of muscarinic acetylcholine receptors was found in layer I. From layer II/III to layer V binding decreases continueously reaching a constant binding level in layers V and VI. This laminar pattern of muscarinic receptor density differs somewhat from that observed in the non-visual cortical regions examined: layer II/III contained the highest receptor density followed by layer I and IV: lowest density was found in layer V and VI. The binding profile of the muscarinic cholinergic M1-subtype through the visual cortex shows a peak in cortical layer II and in the upper part of layer VI, whereas in the non-visual cortical regions cited the binding level was high in layer II/III, moderate in layer I and IV, and low in layer VI. Layers I to IV of the visual cortex contained the highest beta-adrenergic receptor densities, whereas only low binding levels were observed in the deeper layers. A similar laminar distribution was found also in the frontal, somatosensory and motor cortex. The density of noradrenaline uptake sites was high in all layers of the cortical regions studied, but with noradrenaline uptake sites somewhat more concentrated in the superficial layers than in deeper ones. The distinct laminar pattern of cholinergic and noradrenergic receptor sites indicates a different role for acetylcholine and noradrenaline in the functional anatomy of the cerebral cortex, and in particular, the visual cortex. (author)

  9. Laminar pattern of cholinergic and adrenergic receptors in rat visual cortex using quantitative receptor autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Schliebs, R; Walch, C [Leipzig Univ. (German Democratic Republic). Bereich Medizin; Stewart, M G [Open Univ., Milton Keynes (UK)

    1989-01-01

    The laminar distribution of muscarinic acetylcholine receptors, including the M1-receptor subtype, of beta-adrenergic receptors, and noradrenaline uptake sites, was studied in the adult rat visual, frontal, somatosensory and motor cortex, using quantitative receptor autoradiography. In the visual cortex, the highest density of muscarinic acetylcholine receptors was found in layer I. From layer II/III to layer V binding decreases continueously reaching a constant binding level in layers V and VI. This laminar pattern of muscarinic receptor density differs somewhat from that observed in the non-visual cortical regions examined: layer II/III contained the highest receptor density followed by layer I and IV: lowest density was found in layer V and VI. The binding profile of the muscarinic cholinergic M1-subtype through the visual cortex shows a peak in cortical layer II and in the upper part of layer VI, whereas in the non-visual cortical regions cited the binding level was high in layer II/III, moderate in layer I and IV, and low in layer VI. Layers I to IV of the visual cortex contained the highest beta-adrenergic receptor densities, whereas only low binding levels were observed in the deeper layers. A similar laminar distribution was found also in the frontal, somatosensory and motor cortex. The density of noradrenaline uptake sites was high in all layers of the cortical regions studied, but with noradrenaline uptake sites somewhat more concentrated in the superficial layers than in deeper ones. The distinct laminar pattern of cholinergic and noradrenergic receptor sites indicates a different role for acetylcholine and noradrenaline in the functional anatomy of the cerebral cortex, and in particular, the visual cortex. (author).

  10. The influence of occupational heat exposure on cognitive performance and blood level of stress hormones: a field study report.

    Science.gov (United States)

    Mazlomi, Adel; Golbabaei, Farideh; Farhang Dehghan, Somayeh; Abbasinia, Marzieh; Mahmoud Khani, Somayeh; Ansari, Mohammad; Hosseini, Mostafa

    2017-09-01

    This article aimed to investigate the effect of heat stress on cognitive performance and the blood concentration of stress hormones among workers of a foundry plant. Seventy workers within the exposed (35 people) and unexposed (35 people) groups were studied. The wet bulb globe temperature (WBGT) index was measured for heat stress assessment. The cognitive performance tests were conducted using the Stroop color word test (SCWT) before and during working hours. For the assessment of the serum level of cortisol and the plasma level of adrenaline and noradrenaline, blood samples were taken during working hours from both groups. Only for SCWT III was there a significant relationship between heat stress and test duration, error rate and reaction time. The laboratory test results revealed significantly higher concentrations of cortisol, adrenaline and noradrenaline in the exposed subjects than in the unexposed group. There existed a positive correlation between cortisol, adrenaline, noradrenaline and WBGT index and also test duration and reaction time of SCWT III, and number of errors of SCWT I, SCWT II and SCWT III during work. Heat stress can lead to an increase in the blood level of stress hormones, resulting in cognitive performance impairment.

  11. Catecholamine levels in sheep hypothalamus, hypophysis and adrenals following whole-body gamma irradiation

    International Nuclear Information System (INIS)

    Pastorova, B.; Arendarcik, J.; Molnarova, M.

    1985-01-01

    Changes were studied in the levels of catecholamines and L-DOPA in the control system of the reproduction cycle (hypothalamus, hypophysis) and in the adrenal glands of sheep after whole-body irradiation with 60 Co at a total dose of 6.7 Gy for seven days. The output of the radiation source was 0.039 Gy/h. The catecholamines (noradrenaline, dopamine and adrenaline) and L-DOPA were determined after separation from the tissues by the method of spectral fluorometry. After whole-body exposure to gamma radiation, noradrenaline dropped in the hypothalamus in comparison with the control group, most significantly in the rostral (by 74.2%) and caudal (by 40%) parts. A similar drop was also observed in dopamine, the concentrations of which decreased in the rostral hypothalamus by 60%. Adrenaline showed a drop in the hypothalamus, most significant in the caudal region (by 62%). Consequently, the level of the precursor of the synthesis of catecholamines and L-DOPA changed and showed in the studied regions of the hypothalamus significantly lower levels than in the control group. As regards the hypophysis, after irradiation no significant changes in the levels of noradrenaline and adrenaline were recorded, however, dopamine and L-DOPA dropped significantly (P<0.01). The exposure to gamma radiation also causes a decrease in the concentrations of catecholamines and L-DOPA in the adrenal glands of sheep, most significantly in noradrenaline (by 61%). It was thus found that whole-body irradiation of sheep with a dose of 6.7 Gy results in a significant decrease in the level of catecholamines in the hypothalamus, hypophysis and adrenal glands, which is probably in relation to the failure of synthesis and degradation of catecholamines and to the total organism injury

  12. The water avoidance stress induces bladder pain due to a prolonged alpha1A adrenoceptor stimulation.

    Science.gov (United States)

    Matos, Rita; Serrão, Paula; Rodriguez, Larissa; Birder, Lori Ann; Cruz, Francisco; Charrua, Ana

    2017-08-01

    Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) remains an elusive disease with the cause for the pain unclear. BPS/IC patients present increased sympathetic activity and high levels of urinary noradrenaline. At the experimental level, it has been shown that chronic adrenergic stimulation produces pain and bladder changes through an alpha 1A adrenoceptor mediated mechanism. Water avoidance stress (WAS) in rodents reproduces signs of nociception and bladder changes seen in BPS/IC patients. In this study, we explore the possible role of alpha 1A adrenoceptor in bladder pain and morphological changes. WAS was induced in a group of female Wistar rats. A separate WAS group received 0.2 mg/kg day silodosin (WAS + S). Lower abdominal pain was determined by performing sensitivity to Von Frey filaments. Bladder reflex activity was determined by cystometry in anaesthetised animals. Urine was collected for noradrenaline quantification by HPLC. Bladders were harvested and stained with Haematoxylin-eosin (to analyse urothelial morphology and to determine the disruption of surface umbrella cells) or with Toluidine Blue 0.1% to analyse mast cell infiltration. WAS increased urinary noradrenaline level and bladder frequency and decreased mechanical pain threshold, which was reversed by silodosin. WAS induced lymphocytic and mast cells infiltration in the mucosa and mild urothelial disruption, which was absent in WAS + S group. Alpha 1A adrenoceptor stimulation has an important role in the appearance of bladder pain in rats. Since BPS/IC patients present high levels of noradrenaline, alpha 1A stimulation may be an additional trigger for bladder dysfunction presented by these patients. Further studies will determine the clinical relevance of this finding in the treatment of BPS/IC patients.

  13. Plasma catecholamine and serum gastrin concentrations during sham feeding

    DEFF Research Database (Denmark)

    Bekker, Carsten; Andersen, D; Kronborg, O

    1983-01-01

    Plasma adrenaline, plasma noradrenaline and serum gastrin concentrations were measured before and after sham feeding in eight patients with duodenal ulcer and in four normal subjects. No significant change in the concentrations was observed after sham feeding. In three patients with duodenal ulce...... groups. It is concluded that sympathetic nervous activity and serum gastrin concentrations are not influenced by sham feeding in contrast to the influence of insulin hypoglycemia....... an insulin test resulted in a 25-fold rise in plasma adrenaline. The ulcer patients showed significantly higher levels of plasma adrenaline and plasma noradrenaline than the normal subjects both before and after sham feeding, and this difference was probably not caused only by age difference in the two...

  14. Effect of catecholamines and insulin on plasma volume and intravascular mass of albumin in man

    DEFF Research Database (Denmark)

    Hilsted, J; Christensen, N J; Larsen, S

    1989-01-01

    1. The effect of intravenous catecholamine infusions and of intravenous insulin on plasma volume and intravascular mass of albumin was investigated in healthy males. 2. Physiological doses of adrenaline (0.5 microgram/min and 3 microgram/min) increased peripheral venous packed cell volume...... significantly; intravenous noradrenaline at 0.5 microgram/min had no effect on packed cell volume, whereas packed cell volume increased significantly at 3 micrograms of noradrenaline/min. No significant change in packed cell volume was found during saline infusion. 3. During adrenaline infusion at 6 micrograms...... in packed cell volume, plasma volume, intravascular mass of albumin and transcapillary escape rate of albumin during hypoglycaemia may be explained by the combined actions of adrenaline and insulin....

  15. Effects of exercise on the desire to smoke and physiological responses to temporary smoking abstinence: a crossover trial.

    Science.gov (United States)

    Roberts, Vaughan; Gant, Nicholas; Sollers, John J; Bullen, Chris; Jiang, Yannan; Maddison, Ralph

    2015-03-01

    Exercise has been shown to attenuate cigarette cravings during temporary smoking abstinence; however, the mechanisms of action are not clearly understood. The objectives of the study were to compare the effects of three exercise intensities on desire to smoke and explore potential neurobiological mediators of desire to smoke. Following overnight abstinence, 40 participants (25 males, 18-59 years) completed three 15 min sessions of light-, moderate-, or vigorous-intensity exercise on a cycle ergometer in a randomized crossover design. Ratings of desire to smoke were self-reported pre- and post-exercise and heart rate variability was measured throughout. Saliva and blood were analyzed for cortisol and noradrenaline in a sub-sample. Exercise influenced desire to smoke (F [2, 91] = 7.94, p exercise. There were also significant time x exercise intensity interaction effects for heart rate variability and plasma noradrenaline (F [8, 72] = 2.23, p = 0.03), with a bias in noradrenaline occurring between light and vigorous conditions (adjusted mean difference [SE] = 2850 ng/ml [592], p exercise. There was no interaction of time x exercise intensity for plasma and salivary cortisol levels. These findings support the use of vigorous exercise to reduce cigarette cravings, showing potential alterations in a noradrenergic marker.

  16. What do monoamines do in pain modulation?

    Science.gov (United States)

    Bannister, Kirsty; Dickenson, Anthony H

    2016-06-01

    Here, we give a topical overview of the ways in which brain processing can alter spinal pain transmission through descending control pathways, and how these change in pain states. We link preclinical findings on the transmitter systems involved and discuss how the monoamines, noradrenaline, 5-hydroxytryptamine (5-HT), and dopamine, can interact through inhibitory and excitatory pathways. Descending pathways control sensory events and the actions of the neurotransmitters noradrenaline and 5-HT in the dorsal horn of the spinal cord are chiefly implicated in nociception or antinociception according to the receptor that is activated. Abnormalities in descending controls effect central pain processing. Following nerve injury a noradrenaline-mediated control of spinal excitability is lost, whereas its restoration reduces neuropathic hypersensitivity. The story with 5-HT remains more complex because of the myriad of receptors that it can act upon; however the most recent findings support that facilitations may dominate over inhibitions. The monoaminergic system can be manipulated to great effect in the clinic resulting in improved treatment outcomes and is the basis for the actions of the antidepressant drugs in pain. Looking to the future, prediction of treatment responses will possible by monitoring a form of inhibitory descending control for optimized pain relief.

  17. Atomoxetine treatment may decrease striatal dopaminergic transporter availability after 8 weeks: pilot SPECT report of three cases

    Directory of Open Access Journals (Sweden)

    Akay AP

    2015-11-01

    Full Text Available Aynur Pekcanlar Akay,1 Gamze Capa Kaya,2,3 Burak Baykara,1 Yusuf Demir,2,3 Handan Özek,1 Sevay Alsen,1 Mine Sencan Eren,2,3 Neslihan Inal Emiroglu,1 Turkan Ertay,2,3 Yesim Ozturk,4 Suha Miral,1 Hatice Durak,2,3 Evren Tufan4 1Department of Child and Adolescent Psychiatry, 2Department of Nuclear Medicine, 3Department of Pediatrics, Dokuz Eylul University Medical Faculty, Izmir, 4Department of Child and Adolescent Psychiatry, Abant İzzet Baysal University, Bolu, Turkey Abstract: Attention deficit/hyperactivity disorder is one of the most common neurodevelopmental disorders. The pathophysiology is thought to involve noradrenaline and dopamine. The role of dopamine transporter (DAT was evaluated in imaging studies using mostly dopamine reuptake inhibitors. Atomoxetine is a selective noradrenaline reuptake inhibitor. Here we report the results of a pilot study conducted to evaluate changes in striatal DAT after 8 weeks of atomoxetine treatment. Our results suggest that 8 weeks of atomoxetine treatment may change striatal DAT bioavailability as measured via SPECT but that change was not correlated with genotype or clinical improvement. Keywords: neuroimaging, dopamine, noradrenaline, SLC6A3 protein, human, pragmatic clinical trial, pilot study

  18. Young coconut water ameliorates depression via modulation of neurotransmitters: possible mechanism of action.

    Science.gov (United States)

    Rao, Sadia Saleem; Najam, Rahila

    2016-10-01

    In the current era, plants are frequently tested for its antidepressant potential. Therefore young coconut water, a commonly used plant based beverage, was selected to explore its antidepressant potential. Rodents were selected for this study and forced swim test was conducted to explore antidepressant activity. Analysis of brain biogenic amines using high performance liquid chromatography coupled with electrochemical detection and potentiation of noradrenaline toxicity model were also incorporated in this study to demonstrate probable antidepressant mechanism of action. Coconut water was administered orally at the dose of 4 ml/100 g. Young coconut water showed highly significant increase in struggling time (p coconut water. In noradrenaline toxicity model, it was observed that young coconut water is not a good adrenergic component as its lethality percentage in this test was observed 0 % unlike imipramine which showed lethality of 100 %. High performance liquid chromatography-electrochemical detection of rodent's brain revealed decline in 5-hydroxytryptamine, noradrenaline and dopamine, with concomitant decline in metabolites 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, homovanillic acid and increase in 5-hydroxyindoleacetic acid/5-hydroxytryptamine ratio. Findings from the exploration of monoamines suggest antidepressant effect of young coconut water via homeostasis of monoamines synthesis.

  19. Chronic Stress Improves NO- and Ca2+ Flux-Dependent Vascular Function: A Pharmacological Study

    Energy Technology Data Exchange (ETDEWEB)

    Bruder-Nascimento, Thiago, E-mail: bruderthiago@usp.br [Departamento de Farmacologia - Instituto de Biociências de Botucatu - Universidade do Estado de São Paulo (UNESP), Botucatu, São Paulo (Brazil); Departamento de Clínica Médica - Faculdade de Medicina de Botucatu - Universidade do Estado de São Paulo (UNESP), Botucatu, São Paulo (Brazil); Campos, Dijon Henrique Salome [Departamento de Clínica Médica - Faculdade de Medicina de Botucatu - Universidade do Estado de São Paulo (UNESP), Botucatu, São Paulo (Brazil)

    2015-03-15

    Stress is associated with cardiovascular diseases. This study aimed at assessing whether chronic stress induces vascular alterations, and whether these modulations are nitric oxide (NO) and Ca2+ dependent. Wistar rats, 30 days of age, were separated into 2 groups: control (C) and Stress (St). Chronic stress consisted of immobilization for 1 hour/day, 5 days/week, 15 weeks. Systolic blood pressure was assessed. Vascular studies on aortic rings were performed. Concentration-effect curves were built for noradrenaline, in the presence of L-NAME or prazosin, acetylcholine, sodium nitroprusside and KCl. In addition, Ca{sup 2+} flux was also evaluated. Chronic stress induced hypertension, decreased the vascular response to KCl and to noradrenaline, and increased the vascular response to acetylcholine. L-NAME blunted the difference observed in noradrenaline curves. Furthermore, contractile response to Ca{sup 2+} was decreased in the aorta of stressed rats. Our data suggest that the vascular response to chronic stress is an adaptation to its deleterious effects, such as hypertension. In addition, this adaptation is NO- and Ca{sup 2+}-dependent. These data help to clarify the contribution of stress to cardiovascular abnormalities. However, further studies are necessary to better elucidate the mechanisms involved in the cardiovascular dysfunction associated with stressors. (Arq Bras Cardiol. 2014; [online].ahead print, PP.0-0)

  20. Response of the adrenal medulla to exogenous insulin in head X-irradiated dogs

    International Nuclear Information System (INIS)

    Yamashita, K.; Mieno, M.; Shimizu, T.

    1976-01-01

    The observed results on the secretory response of the adrenal medulla to exogenous insulin in dogs whose heads had been irradiated with 200 rad X-irradiation at a rate of 60.6 rad/min are reported. Approximately 20 h after irradiation 2 i.u. insulin/kg body weight was administered to both irradiated and control (non-irradiated) dogs. The secretion of both adrenaline and noradrenaline in five control dogs which received insulin had increased markedly 30 min after the injection and it was sustained over the first 120 min. Five irradiated dogs also responded to the injection of insulin by secreting appreciable amounts of both adrenaline and noradrenaline, but the responsiveness was considerably lower; adrenaline and noradrenaline secretion 30 and 60 min after the injection was 59 and 33% less than that caused by insulin in control animals respectively, and these differences were significant (P < 0.01). Since insulin induces hypoglycaemia and thereby leads to an increase in the adrenal medullary secretion through the central mechanism, the present results observed 1 day after X-irradiation of the head indicate that the susceptibility of the adrenomedullary activating mechanism in the central nervous system may be diminished considerably after X-irradiation, even at doses as low as 200 rad. (U.K.)

  1. Dopamine beta-hydroxylase deficiency

    Directory of Open Access Journals (Sweden)

    Senard Jean-Michel

    2006-03-01

    Full Text Available Abstract Dopamine beta-hydroxylase (DβH deficiency is a very rare form of primary autonomic failure characterized by a complete absence of noradrenaline and adrenaline in plasma together with increased dopamine plasma levels. The prevalence of DβH deficiency is unknown. Only a limited number of cases with this disease have been reported. DβH deficiency is mainly characterized by cardiovascular disorders and severe orthostatic hypotension. First symptoms often start during a complicated perinatal period with hypotension, muscle hypotonia, hypothermia and hypoglycemia. Children with DβH deficiency exhibit reduced ability to exercise because of blood pressure inadaptation with exertion and syncope. Symptoms usually worsen progressively during late adolescence and early adulthood with severe orthostatic hypotension, eyelid ptosis, nasal stuffiness and sexual disorders. Limitation in standing tolerance, limited ability to exercise and traumatic morbidity related to falls and syncope may represent later evolution. The syndrome is caused by heterogeneous molecular alterations of the DBH gene and is inherited in an autosomal recessive manner. Restoration of plasma noradrenaline to the normal range can be achieved by therapy with the synthetic precursor of noradrenaline, L-threo-dihydroxyphenylserine (DOPS. Oral administration of 100 to 500 mg DOPS, twice or three times daily, increases blood pressure and reverses the orthostatic intolerance.

  2. The impact of acute stress on hormones and cytokines, and how their recovery is affected by music-evoked positive mood.

    Science.gov (United States)

    Koelsch, Stefan; Boehlig, Albrecht; Hohenadel, Maximilian; Nitsche, Ines; Bauer, Katrin; Sack, Ulrich

    2016-03-29

    Stress and recovery from stress significantly affect interactions between the central nervous system, endocrine pathways, and the immune system. However, the influence of acute stress on circulating immune-endocrine mediators in humans is not well known. Using a double-blind, randomized study design, we administered a CO2 stress test to n = 143 participants to identify the effects of acute stress, and recovery from stress, on serum levels of several mediators with immune function (IL-6, TNF-α, leptin, and somatostatin), as well as on noradrenaline, and two hypothalamic-pituitary-adrenal axis hormones (ACTH and cortisol). Moreover, during a 1 h-recovery period, we repeatedly measured these serum parameters, and administered an auditory mood-induction protocol with positive music and a neutral control stimulus. The acute stress elicited increases in noradrenaline, ACTH, cortisol, IL-6, and leptin levels. Noradrenaline and ACTH exhibited the fastest and strongest stress responses, followed by cortisol, IL-6 and leptin. The music intervention was associated with more positive mood, and stronger cortisol responses to the acute stressor in the music group. Our data show that acute (CO2) stress affects endocrine, immune and metabolic functions in humans, and they show that mood plays a causal role in the modulation of responses to acute stress.

  3. Response of the adrenal medulla to exogenous insulin in head X-irradiated dogs

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, K; Mieno, M; Shimizu, T [Nagasaki Univ. (Japan). School of Medicine

    1976-12-01

    The observed results on the secretory response of the adrenal medulla to exogenous insulin in dogs whose heads had been irradiated with 200 rad X-irradiation at a rate of 60.6 rad/min are reported. Approximately 20 h after irradiation 2 i.u. insulin/kg body weight was administered to both irradiated and control (non-irradiated) dogs. The secretion of both adrenaline and noradrenaline in five control dogs which received insulin had increased markedly 30 min after the injection and it was sustained over the first 120 min. Five irradiated dogs also responded to the injection of insulin by secreting appreciable amounts of both adrenaline and noradrenaline, but the responsiveness was considerably lower; adrenaline and noradrenaline secretion 30 and 60 min after the injection was 59 and 33% less than that caused by insulin in control animals respectively, and these differences were significant (P < 0.01). Since insulin induces hypoglycaemia and thereby leads to an increase in the adrenal medullary secretion through the central mechanism, the present results observed 1 day after X-irradiation of the head indicate that the susceptibility of the adrenomedullary activating mechanism in the central nervous system may be diminished considerably after X-irradiation, even at doses as low as 200 rad.

  4. Differential in vivo regulation of TH and DBH mRNA in rat atria by maprotiline and fluoxetine

    Directory of Open Access Journals (Sweden)

    Spasojević Nataša

    2011-01-01

    Full Text Available It is well known that antidepressants affect central monoaminergic neurotransmission and that they also modulate hormone release in peripheral tissues. Repeated maprotiline (a noradrenaline reuptake inhibitor and fluoxetine (a serotonin reuptake inhibitor treatment on gene expression of the catecholamine biosynthetic enzymes were examined in rat atria and ventricles in vivo. Maprotiline decreased the gene expression of tyrosine hydroxylase (TH and dopamineβ-hydroxylase (DBH in the rat atrium. Fluoxetine increased gene expression of TH and DBH, but not of phenylethanolamine N-methyltransferase (PNMT. Chronic application of antidepressants did not change the expression of these enzymes in the ventricles. We conclude that repeated administration of fluoxetine enhances gene transcription of TH and DBH and subsequently stimulates noradrenaline synthesis in rat atria in vivo.

  5. Quantification of [11C]yohimbine binding to α2 adrenoceptors in rat brain in vivo

    DEFF Research Database (Denmark)

    Phan, Jenny-Ann; Landau, Anne M.; Wong, Dean F.

    2015-01-01

    We quantified the binding potentials (BPND) of [11C]yohimbine binding in rat brain to alpha-2 adrenoceptors to evaluate [11C]yohimbine as an in vivo marker of noradrenergic neurotransmission and to examine its sensitivity to the level of noradrenaline. Dual [11C]yohimbine dynamic positron emissio...... is sensitive to a challenge known to increase the extracellular level of noradrenaline, which can benefit future PET investigations of pathologic conditions related to disrupted noradrenergic neurotransmission....... challenge with amphetamine induced a significant decline of [11C]yohimbine BPND of ∼38% in all volumes of interest. The BPND was greatest in the thalamus and striatum, followed in descending order by, frontal cortex, pons, and cerebellum. The experimental data demonstrate that [11C]yohimbine binding...

  6. Serum concentrations of thyroid and adrenal hormones and TSH in men after repeated 1 h-stays in a cold room.

    Science.gov (United States)

    Korhonen, I; Hassi, J; Leppäluoto, J

    2001-11-01

    We exposed six healthy men to 1-h cold air (10 degrees C) daily for 11 days and measured adrenal and thyroid hormones and TSH in serum before and after the cold air exposure on days 0, 5 and 10. We observed that on days 0, 5 and 10 the resting levels and the levels after the cold exposure in serum adrenaline, thyroid hormones and TSH did not significantly change, whereas the serum noradrenaline levels showed a significant 2.2-2.5-fold increase in response to the cold air exposures. The increases were similar indicating that the subjects did not show signs of habituation in their noradrenaline responses. Therefore the 1-h cold air exposure is not sufficiently intensive to reduce the cold-induced sympathetic response.

  7. The CSF and arterial to internal jugular venous hormonal differences during exercise in humans

    DEFF Research Database (Denmark)

    Dalsgaard, Mads K; Ott, Peter; Dela, Flemming

    2004-01-01

    the brain (a-v diff) of hormones that could influence its carbohydrate uptake (n= 9). In addition, neuroendocrine activity and a potential uptake of hormones via the cerebrospinal fluid (CSF) were assessed by lumbar puncture postexercise and at rest (n= 6). Exercise increased the arterial concentration...... of noradrenaline and adrenaline, but there was no cerebral uptake. However, following exercise CSF noradrenaline was 1.4 (0.73-5.5) nmol l(-1), and higher than at rest, 0.3 (0.19-1.84) nmol l(-1) (P ...)(+) and its a-v diff, which increased from 1 (-12 to 5) to 17 (5-41) micromol l(-1) (P CSF NH(4)(+) was reduced to 7 (0-10) versus 11 (7-16) micromol l(-1) (P

  8. Traumatic Endotheliopathy

    DEFF Research Database (Denmark)

    Johansson, Pär I.; Henriksen, Hanne H; Stensballe, Jakob

    2017-01-01

    cohorts and animal models but needs confirmation in a large independent patient cohort. METHODS: Prospective observational study of 424 trauma patients admitted to a level 1 Trauma Center. Admission plasma levels of catecholamines (adrenaline, noradrenaline) and biomarkers reflecting endothelial damage...... (syndecan-1, thrombomodulin, and sE-selectin) were measured and demography, injury type and severity, physiology, treatment, and mortality up till 28 days were recorded. RESULTS: Patients had a median ISS of 17 with 72% suffering from blunt injury. Adrenaline and noradrenaline correlated with syndecan-1 (r...... = 0.38, Padrenaline was the only independent predictor of syndecan-1 by multiple linear regression adjusted for age, injury severity score, Glascow Coma Scale, systolic blood pressure, base excess, platelet count, hemoglobin, prehospital plasma...

  9. The dopamine beta-hydroxylase inhibitor nepicastat increases dopamine release and potentiates psychostimulant-induced dopamine release in the prefrontal cortex.

    Science.gov (United States)

    Devoto, Paola; Flore, Giovanna; Saba, Pierluigi; Bini, Valentina; Gessa, Gian Luigi

    2014-07-01

    The dopamine-beta-hydroxylase inhibitor nepicastat has been shown to reproduce disulfiram ability to suppress the reinstatement of cocaine seeking after extinction in rats. To clarify its mechanism of action, we examined the effect of nepicastat, given alone or in association with cocaine or amphetamine, on catecholamine release in the medial prefrontal cortex and the nucleus accumbens, two key regions involved in the reinforcing and motivational effects of cocaine and in the reinstatement of cocaine seeking. Nepicastat effect on catecholamines was evaluated by microdialysis in freely moving rats. Nepicastat reduced noradrenaline release both in the medial prefrontal cortex and in the nucleus accumbens, and increased dopamine release in the medial prefrontal cortex but not in the nucleus accumbens. Moreover, nepicastat markedly potentiated cocaine- and amphetamine-induced extracellular dopamine accumulation in the medial prefrontal cortex but not in the nucleus accumbens. Extracellular dopamine accumulation produced by nepicastat alone or by its combination with cocaine or amphetamine was suppressed by the α2 -adrenoceptor agonist clonidine. It is suggested that nepicastat, by suppressing noradrenaline synthesis and release, eliminated the α2 -adrenoceptor mediated inhibitory mechanism that constrains dopamine release and cocaine- and amphetamine-induced dopamine release from noradrenaline or dopamine terminals in the medial prefrontal cortex. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

  10. Tyrosine hydroxylase (TH), its cofactor tetrahydrobiopterin (BH4), other catecholamine-related enzymes, and their human genes in relation to the drug and gene therapies of Parkinson's disease (PD): historical overview and future prospects.

    Science.gov (United States)

    Nagatsu, Toshiharu; Nagatsu, Ikuko

    2016-11-01

    Tyrosine hydroxylase (TH), which was discovered at the National Institutes of Health (NIH) in 1964, is a tetrahydrobiopterin (BH4)-requiring monooxygenase that catalyzes the first and rate-limiting step in the biosynthesis of catecholamines (CAs), such as dopamine, noradrenaline, and adrenaline. Since deficiencies of dopamine and noradrenaline in the brain stem, caused by neurodegeneration of dopamine and noradrenaline neurons, are mainly related to non-motor and motor symptoms of Parkinson's disease (PD), we have studied human CA-synthesizing enzymes [TH; BH4-related enzymes, especially GTP-cyclohydrolase I (GCH1); aromatic L-amino acid decarboxylase (AADC); dopamine β-hydroxylase (DBH); and phenylethanolamine N-methyltransferase (PNMT)] and their genes in relation to PD in postmortem brains from PD patients, patients with CA-related genetic diseases, mice with genetically engineered CA neurons, and animal models of PD. We purified all human CA-synthesizing enzymes, produced their antibodies for immunohistochemistry and immunoassay, and cloned all human genes, especially the human TH gene and the human gene for GCH1, which synthesizes BH4 as a cofactor of TH. This review discusses the historical overview of TH, BH4-, and other CA-related enzymes and their genes in relation to the pathophysiology of PD, the development of drugs, such as L-DOPA, and future prospects for drug and gene therapy for PD, especially the potential of induced pluripotent stem (iPS) cells.

  11. Effect of forskolin and prostaglandin E1 on stimulus secretion coupling in cultured bovine adrenal chromaffin cells.

    Science.gov (United States)

    Marriott, D; Adams, M; Boarder, M R

    1988-02-01

    Treatment of adrenal chromaffin cells with forskolin (0.1-10 microM) stimulated cyclic AMP levels, reduced the maximal stimulation of release of noradrenaline by nicotine, and increased release in response to elevated external potassium and the calcium ionophore A23187. The presence of the phosphodiesterase inhibitor Ro 20-17-24 with forskolin potentiated both the stimulation of cyclic AMP and the inhibition of nicotine-induced noradrenaline release. Dibutyryl cyclic AMP, and the elevation of cyclic AMP with prostaglandin E1, also attenuated nicotine-stimulated release. However, when the stimulation of intracellular cyclic AMP production by prostaglandin E1 was potentiated by low levels of forskolin, there was not a concomitant potentiation of effect on noradrenaline release. Dideoxyforskolin, an analogue of forskolin which does not stimulate adenylate cyclase, inhibited both potassium- and nicotine-stimulated release, probably by a mechanism unrelated to the action of forskolin in these experiments. Using Fura-2 to estimate free intracellular calcium levels, both forskolin and dideoxyforskolin (at 10 microM) reduced the calcium transient in response to nicotine. These results support a model in which elevation of cyclic AMP inhibits the activation of nicotinic receptors, but augments stimulus secretion coupling downstream of calcium entry. The data, however, do not indicate a simple relationship between total intracellular cyclic AMP levels and the attenuation of nicotinic stimulation of release.

  12. Novel double-isotope technique for enzymatic assay of catecholamines, permitting high precision, sensitivity and plasma sample capacity

    International Nuclear Information System (INIS)

    Brown, M.J.; Jenner, D.A.

    1981-01-01

    A novel use of a double-isotope method is described which allows radioenzymatic assays to combine precision and sensitivity. In the catechol O-methyltransferase assay separate portions of each plasma sample are incubated with either S-[ 3 H]- or S-[ 14 C]-adenosyl-L-methionine. Standards of noradrenaline and adrenaline are added to the latter portions and are thus converted into standards of [ 14 C]metadrenalines. These are added to the 3 H-labelled portions after the incubation, where they function as tracers. The final recovery of 14 C radioactivity corrects for (a) the efficiency of methylation in the plasma sample concerned and (b) the recovery of metadrenalines during the extraction procedures. The 3 H/ 14 C ratio is constant in each assay for a given catecholamine concentration and is determined for samples to which standards of noradrenaline and adrenaline are added to the 3 H- (as well as the 14 C-) labelled portions before the initial incubation. The sensitivity of the assay is increased by using high specific radioactivity S-[ 3 H]adenosyl-L-methionine, and low backgrounds are maintained by catecholamine depletion in vivo in the rats used for enzyme preparation. Both catecholamines (1.5 pg/ml; 10 pmol/l) may be detected; the coefficients of variation are 3.0 and 3.2% for noradrenaline and adrenaline respectively (intra-assay) and 4.6 and 5.0% (inter-assay). (author)

  13. Development and aminergic neuromodulation of a spinal locomotor network controlling swimming in Xenopus larvae.

    Science.gov (United States)

    Sillar, K T; Reith, C A; McDearmid, J R

    1998-11-16

    In this article we review our research on the development and intrinsic neuromodulation of a spinal network controlling locomotion in a simple vertebrate. Swimming in hatchling Xenopus embryos is generated by a restricted network of well-characterized spinal neurons. This network produces a stereotyped motor pattern which, like real swimming, involves rhythmic activity that alternates across the body and progresses rostrocaudally with a brief delay between muscle segments. The stereotypy results from motoneurons discharging a single impulse in each cycle; because all motoneurons appear to behave similarly there is little scope for altering the output to the myotomes from one cycle to the next. Just one day later, however, Xenopus larvae generate a more complex and flexible motor pattern in which motoneurons can discharge a variable number of impulses which contribute to ventral root bursts in each cycle. This maturation of swimming is due, in part, to the influence of serotonin released from brain-stem raphespinal interneurons whose axonal projections innervate the cord early in larval life. Larval swimming is differentially modulated by both serotonin and by noradrenaline: serotonin leads to relatively fast, intense swimming whereas noradrenaline favors slower, weaker activity. Thus, these two biogenic amines select opposite extremes from the spectrum of possible output patterns that the swimming network can produce. Our studies on the cellular and synaptic effects of the amines indicate that they can control the strength of reciprocal glycinergic inhibition in the spinal cord. Serotonin and noradrenaline act presynaptically on the terminals of glycinergic commissural interneurons to weaken and strengthen, respectively, crossed glycinergic inhibition during swimming. As a result, serotonin reduces and noradrenaline increases interburst intervals. The membrane properties of spinal neurons are also affected by the amines. In particular, serotonin can induce

  14. 282_Shehu et al.,_BAJOPAS MANUSCRIPT _2

    African Journals Online (AJOL)

    user pc

    2017-12-02

    Dec 2, 2017 ... us, the current study aimed at evaluating the antidepressant activity of virosa in mice. The acute ..... is alteration in neurotransmitters function, particularly serotonin, noradrenaline and dopamine (Mayor, 2014;. Argyii, 2015 ...

  15. Mania and depression explained

    African Journals Online (AJOL)

    are thought to play a role in neuro-developmental processes, lending further ... Because serotonin, noradrenaline and dopamine are strongly implicated in the .... Genome-wide association study reveals two new risk loci for bipolar disorder.

  16. [Hereditary factors in attention deficit hyperactivity disorder

    NARCIS (Netherlands)

    Fliers, E.A.; Franke, B.

    2005-01-01

    Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by concentration problems, hyperactivity and impulsivity. Disturbances in dopamine and/or noradrenalin neurotransmission are probably the underlying pathophysiological mechanisms of ADHD. Around 80% of

  17. Mechanisms underlying the noradrenergic modulation of longitudinal coordination during swimming in Xenopus laevis tadpoles

    DEFF Research Database (Denmark)

    Merrywest, Simon D; McDearmid, Jonathan R; Kjaerulff, Ole

    2003-01-01

    Noradrenaline (NA) is a potent modulator of locomotion in many vertebrate nervous systems. When Xenopus tadpoles swim, waves of motor neuron activity alternate across the body and propagate along it with a brief rostro-caudal delay (RC-delay) between segments. We have now investigated the mechani......Noradrenaline (NA) is a potent modulator of locomotion in many vertebrate nervous systems. When Xenopus tadpoles swim, waves of motor neuron activity alternate across the body and propagate along it with a brief rostro-caudal delay (RC-delay) between segments. We have now investigated...... might promote postinhibitory rebound firing. The synaptic inputs during swimming were simulated using a sustained positive current, superimposed upon which were brief negative currents. When these conditions were held constant NA enhanced the probability of rebound firing--indicating a direct effect...

  18. Adrenergic effects on secretion of epidermal growth factor from Brunner's glands

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1985-01-01

    The influence of the sympathetic nervous system and adrenergic agonists on flow rate and secretion of epidermal growth factor (EGF) from Brunner's glands has been investigated in the rat. Chemical sympathectomy by administration of 6-hydroxydopamine increased volume secretion and output of EGF from...... Brunner's glands but depleted the glands of EGF. Infusion of noradrenaline, an alpha-adrenergic agonist, inhibited basal and vasoactive intestinal polypeptide (VIP) stimulated flow rate and output of EGF from Brunner's glands and increased the amount of EGF in the tissue. Vasoactive intestinal polypeptide...... also increased the amount of EGF in Brunner's gland tissue and this was unchanged after simultaneous infusion of VIP and noradrenaline as well as VIP and isoproterenol, a beta-adrenergic agonist. Isoproterenol had no effect on basal and VIP stimulated secretion of EGF from Brunner's glands...

  19. Whole-body function-scintigraphic investigations for the determination of reginal blood volumina and their variations

    International Nuclear Information System (INIS)

    Mostbeck, A.; Partsch, H.

    1976-01-01

    Changes of regional blood volume in the different parts of the body were observed by functional whole body scanning after injection of a tracer which remains sufficiently in the vascular beds to enable acute examinations sup(99m)Tc. In 21 persons changes of regional blood volume compression of both legs) and by pharmacological influences (dihydroergotamine, nifedipine, nitroglycerin, noradrenalin, dopamin). In both venous occlusion and compression of the legs a reciprocal relationship was observed between the blood volume of the legs and that of the central regions of the body. Dihydroergotamine, noradrenalin and dopamin caused a displacement of blood volume towards the central regions. After the application of nitroglycerin there was an increase of blood volume in the arms and in the legs and a distinct decrease of the thoracal blood volume

  20. D-amino acid oxidase activator gene (DAOA) variation affects cerebrospinal fluid homovanillic acid concentrations in healthy Caucasians

    DEFF Research Database (Denmark)

    Andreou, Dimitrios; Saetre, Peter; Werge, Thomas

    2012-01-01

    The D-amino acid oxidase activator (DAOA) protein regulates the function of D-amino oxidase (DAO), an enzyme that catalyzes the oxidative deamination of D-3,4-dihydroxyphenylalanine (D-DOPA) and D-serine. D-DOPA is converted to L-3,4-DOPA, a precursor of dopamine, whereas D-serine participates...... in glutamatergic transmission. We hypothesized that DAOA polymorphisms are associated with dopamine, serotonin and noradrenaline turnover in the human brain. Four single-nucleotide polymorphisms, previously reported to be associated with schizophrenia, were genotyped. Cerebrospinal fluid (CSF) samples were drawn...... by lumbar puncture, and the concentrations of the major dopamine metabolite homovanillic acid (HVA), the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the major noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured. Two of the investigated polymorphisms, rs...

  1. Antidepressants in the treatment of neuropathic pain

    DEFF Research Database (Denmark)

    Sindrup, Søren H.; Otto, Marit; Finnerup, Nanna Brix

    2005-01-01

    Neuropathic pain is due to lesion or dysfunction of the peripheral or central nervous system. Tricyclic antidepressants and anticonvulsants have long been the mainstay of treatment of this type of pain. Tricyclic antidepressants may relieve neuropathic pain by their unique ability to inhibit...... presynaptic reuptake of the biogenic amines serotonin and noradrenaline, but other mechanisms such as N-methyl-D-aspartate receptor and ion channel blockade probably also play a role in their pain-relieving effect. The effect of tricyclic antidepressants in neuropathic pain in man has been demonstrated...... in numerous randomised, controlled trials, and a few trials have shown that serotonin noradrenaline and selective serotonin reuptake inhibitor antidepressants also relieve neuropathic pain although with lower efficacy. Tricyclic antidepressants will relieve one in every 2-3 patients with peripheral...

  2. Individually reared rats

    International Nuclear Information System (INIS)

    Kraeuchi, K.; Gentsch, C.; Feer, H.

    1981-01-01

    The influence of social isolation in rats on postsynaptic alpha 1 - and beta-adrenergic receptors, on the cAMP generating system and on the presynaptic uptake mechanism in the central noradrenergic system was examined in different brain regions. Rearing rats in isolation from the 19th day of life for 12 weeks leads in all regions to a general tendency for a reduction in 3 H-DHA binding, to an enhanced 3 H-WB4101 binding and to a decreased responsiveness of the noradrenaline sensitive cAMP generating system. These changes reach significance only in the pons-medulla-thallamusregion. Isolated rats showed an increased synaptosomal uptake of noradrenaline, most pronounced and significant in the hypothalamus. Our data provide further support for a disturbance in central noradrenergic function in isolated rats. (author)

  3. Poor agreement between transcranial Doppler and near-infrared spectroscopy-based estimates of cerebral blood flow changes in sepsis

    DEFF Research Database (Denmark)

    Toksvang, Linea N; Plovsing, Ronni R; Petersen, Marie W

    2014-01-01

    BACKGROUND: Continuous monitoring of cerebral blood flow (CBF) may be valuable in critically ill patients with sepsis. In this study, we compared spatially resolved near-infrared spectroscopy (NIRS) to transcranial Doppler ultrasound (TCD)-derived estimates of noradrenaline-associated changes...... in CBF in such patients. METHODS: Mean arterial blood pressure (MAP) was elevated by increasing the noradrenaline infusion rate in eight mechanically ventilated, critically ill patients diagnosed with severe sepsis or septic shock. The associated changes in CBF were assessed by simultaneous ipsilateral......-derived estimates with a relative bias of 14% and limits of agreement of -18% to 45% change in CBF. CONCLUSION: Our findings stress that TCD and NIRS cannot be used interchangeably for monitoring changes in cerebral haemodynamics in critically ill patients with sepsis receiving vasopressor treatment...

  4. Establishment of a paediatric age-related reference interval for the measurement of urinary total fractionated metanephrines.

    LENUS (Irish Health Repository)

    Griffin, Alison

    2011-01-01

    Normetanephrine and metanephrine are intermediate metabolites of noradrenaline and adrenaline metabolism. To assess whether normetanephrine and metanephrine analysis may aid in the diagnosis of Neuroblastoma, a reference interval for these metabolites must first be established.

  5. Dynamics of plasma catecholamine and corticosterone concentrations during reinforced and extinguished operant behavior in rats

    NARCIS (Netherlands)

    de Boer, S.F.; de Beun, R; Slangen, J L; van der Gugten, J

    Plasma noradrenaline (NA), adrenaline (A) and corticosterone (CS) concentrations were determined simultaneously in permanently heart-cannulated rats before and during the performance of reinforced and nonreinforced (extinguished) operant behavior. Shortly before the experimental food-reinforced (VI

  6. CHAPTER 1

    African Journals Online (AJOL)

    Dr Olaleye

    Official Publication of the African Association of Physiological Sciences ... noradrenaline (NA)-evoked vascular responses in carotid circulation in rats. Furthermore, whether the .... PowerLab/8S at 100 Hz and connected to a computer by Chart ...

  7. The importance of neurotransmitters in the central control of the blood pressure

    International Nuclear Information System (INIS)

    Pfitscher-Klausmair, A.

    1990-12-01

    In anaesthetized cats, the nucleus tractus solitarii (NTS) and the locus coeruleus (LC) were bilaterally superfused through push-pull cannulae with artificial cerebrospinal fluid. Catecholamines were determined in the superfusate by a radioenzymatic assay, gamma-aminobutyric acid (GABA) was determined in the superfusate and homogenitate with glutamate by an enzymatic and fluorimetric assay. In the NTS and LC the resting release of catecholamines varied rhythmically. To investigate the function of catecholaminergic neurons and GABAergic neurons of the NTS in cardiovascular control, the influence of experimentally induced blood pressure changes on the rates of the endogenous catecholamines dopamine,noradrenaline and adrenaline in the NTS was observed. The decreased noradrenaline and adrenaline release elicited by increases in blood pressure and the reduced release of dopamine induced by decreases in blood pressure suggest a hypertensive function on noradrenaline and adrenaline and a hypotensive role of dopamine at the level of the rostral and intermediate NTS. Bilateral carotid occlusion led to a very pronounced increase in the release rate of GABA in the rostral NTS. This result demonstrated the hypertensive function of GABA in the NTS, thus underlining the importance of catecholaminergic and GABAergic neurons of the NTS in central cardiovascular control. The GABA-transaminase inhibitor Vigabatrin was injected in kyoto rats and spontaneously hypertensive rats. GABA-Transaminase inhibition was accompanied by an increase of GABA concentration in the rat brain. The administration of Vigabatrin had no influence on the blood pressure but on body weight of the rats. (author)

  8. Sexual side effects of serotonergic antidepressants: mediated by inhibition of serotonin on central dopamine release?

    Science.gov (United States)

    Bijlsma, Elisabeth Y; Chan, Johnny S W; Olivier, Berend; Veening, Jan G; Millan, Mark J; Waldinger, Marcel D; Oosting, Ronald S

    2014-06-01

    Antidepressant-induced sexual dysfunction adversely affects the quality of life of antidepressant users and reduces compliance with treatment. Animal models provide an instructive approach for examining potential sexual side effects of novel drugs. This review discusses the stability and reproducibility of our standardized test procedure that assesses the acute, subchronic and chronic effects of psychoactive compounds in a 30 minute mating test. In addition, we present an overview of the effects of several different (putative) antidepressants on male rat sexual behavior, as tested in our standardized test procedure. By comparing the effects of these mechanistically distinct antidepressants (paroxetine, venlafaxine, bupropion, buspirone, DOV 216,303 and S32006), this review discusses the putative mechanism underlying sexual side effects of antidepressants and their normalization. This review shows that sexual behavior is mainly inhibited by antidepressants that increase serotonin neurotransmission via blockade of serotonin transporters, while those that mainly increase the levels of dopamine and noradrenaline are devoid of sexual side effects. Those sexual disturbances cannot be normalized by simultaneously increasing noradrenaline neurotransmission, but are normalized by increasing both noradrenaline and dopamine neurotransmission. Therefore, it is hypothesized that the sexual side effects of selective serotonin reuptake inhibitors may be mediated by their inhibitory effects on dopamine signaling in sex brain circuits. Clinical development of novel antidepressants should therefore focus on compounds that simultaneously increase both serotonin and dopamine signaling. © 2013 Elsevier Inc. All rights reserved.

  9. Peripheral markers of serotonergic and noradrenergic function in post-pubertal, caucasian males with autistic disorder.

    Science.gov (United States)

    Croonenberghs, J; Delmeire, L; Verkerk, R; Lin, A H; Meskal, A; Neels, H; Van der Planken, M; Scharpe, S; Deboutte, D; Pison, G; Maes, M

    2000-03-01

    Some studies have suggested that disorders in the peripheral and central metabolism of serotonin (5-HT) and noradrenaline may play a role in the pathophysiology of autistic disorder. This study examines serotonergic and noradrenergic markers in a study group of 13 male, post-pubertal, caucasian autistic patients (age 12-18 y; I.Q. > 55) and 13 matched volunteers. [3H]-paroxetine binding Kd values were significantly higher in patients with autism than in healthy volunteers. Plasma concentrations of tryptophan, the precursor of 5-HT, were significantly lower in autistic patients than in healthy volunteers. There were no significant differences between autistic and normal children in the serum concentrations of 5-HT, or the 24-hr urinary excretion of 5-hydroxy-indoleacetic acid (5-HIAA), adrenaline, noradrenaline, and dopamine. There were no significant differences in [3H]-rauwolscine binding Bmax or Kd values, or in the serum concentrations of tyrosine, the precursor of noradrenaline, between both study groups. There were highly significant positive correlations between age and 24-hr urinary excretion of 5-HIAA and serum tryptophan. The results suggest that: 1) serotonergic disturbances, such as defects in the 5-HT transporter system and lowered plasma tryptophan, may play a role in the pathophysiology of autism; 2) autism is not associated with alterations in the noradrenergic system; and 3) the metabolism of serotonin in humans undergoes significant changes between the ages of 12 and 18 years.

  10. The sympathetic nervous system in polycystic ovary syndrome: a novel therapeutic target?

    Science.gov (United States)

    Lansdown, Andrew; Rees, D Aled

    2012-12-01

    Polycystic ovary syndrome (PCOS) is a common endocrine condition associated with long-term health risks, including type 2 diabetes and vascular dysfunction in addition to reproductive sequelae. Many of the common features of PCOS, such as central obesity, hyperinsulinaemia and obstructive sleep apnoea (OSA), are associated with chronic sympathetic overactivity, suggesting that sympathoexcitation may be involved in the pathogenesis of this condition. Rodent models of polycystic ovaries have shown that ovarian sympathetic outflow may be increased, accompanied by elevated intra-ovarian synthesis of nerve growth factor (NGF) which may be involved in initiation of ovarian pathology. Patients with PCOS have evidence of increased muscle sympathetic nerve activity (MSNA), altered heart rate variability and attenuated heart rate recovery postexercise, compared with age- and BMI-matched controls, suggesting a generalized increase in sympathetic nerve activity. Active weight loss can reduce MSNA and whole body noradrenaline spillover, whereas low-frequency electroacupuncture decreased MSNA in overweight women with PCOS. Treatment of OSA with continuous positive airways pressure may reduce plasma noradrenaline levels and diastolic blood pressure and improve cardiac sympathovagal balance. Renal sympathetic denervation also reduced MSNA, noradrenaline spillover and blood pressure in two PCOS subjects with hypertension, accompanied by improved insulin sensitivity. The sympathetic nervous system may thus offer a new therapeutic target in PCOS but larger and longer-term studies are needed before these treatments can be considered in clinical practice. © 2012 Blackwell Publishing Ltd.

  11. Calcium-sensitivity of smooth muscle contraction in the isolated ...

    African Journals Online (AJOL)

    sensitivity of smooth muscle contraction were studied in the isolated perfused rat tail artery, employing the activators noradrenaline (NA) (3ìM) sand potassium chloride (KC1) (100mM). Experiments were conduced in Ca2+ - buffered saline.

  12. Reaction of blood pressure and mesenteric blood flow to infusion of biogenic amines in normal and supralethally x-irradiated rats

    International Nuclear Information System (INIS)

    Timmermans, R.; Gerber, G.B.

    1980-01-01

    The responss of blood pressure and mesenteric blood flow were recorded during infusion of biogenic amines (noradrenaline, dopamine, serotonin, acetylcholine, and histamine) to control and x-irradiated rats (first and third days after 2 kR x irradiation). Responses to different doses of the amines were evaluated, and the results obtained correspond to those seen in other species (e.g., an increase in pressure and a decrease in flow after dopamine, an increase in pressure and a decrease in flow after serotonin, a decrease in pressure and flow after acetylcholine, and a decrease in flow after serotonin, a decrease in pressure and flow after acetylcholine, and a decrease in pressure and an increase in flow after histamine). Irradiated animals are more responsive to pressure-raising agents, in particular to noradrenaline. They also have an altered dose-pressure response curve for dopamine

  13. A meta-analysis to determine the effect of pharmacological and non-pharmacological treatments on fibromyalgia symptoms comprising OMERACT-10 response criteria.

    Science.gov (United States)

    Papadopoulou, Despoina; Fassoulaki, Argyro; Tsoulas, Christos; Siafaka, Ioanna; Vadalouca, Athina

    2016-03-01

    Fibromyalgia is characterized by widespread pain, sleep problems, fatigue, functional impairment, psychological distress, and cognitive dysfunction. The objective of this meta-analysis is to synthesize the available data on the effectiveness of pharmacological and non-pharmacological interventions across all domains included in the Outcome Measures in Rheumatology Clinical Trials (OMERACT-10) fibromyalgia response definitions, and to examine response based on these definitions. We searched Cochrane, PubMed, Scopus, and the reference lists of articles for randomized controlled trials of any drug formulation or non-pharmacological intervention used for fibromyalgia treatment. We extracted efficacy data regarding pain, sleep, physical function, fatigue, anxiety, depression, and cognition. The available data were insufficient to draw definite conclusions regarding response. Indirect evidence indicates that it may be expected with the use of serotonin noradrenaline reuptake inhibitors (SNRIs), noradrenaline reuptake inhibitors (NRIs), and multidisciplinary treatment.

  14. Synergism of diabetic and inflammatory culture conditions on reactivity of isolated small arteries

    DEFF Research Database (Denmark)

    Blædel, Martin Mads; Boonen, Harrie C.M.; Sams Nielsen, Anette

    Background: Cardiovascular disease (CVD) is the manifestation of atherosclerosis, which has been linked to obesity, the metabolic syndrome (MS) and overt type 2 diabetes (T2DM). Vascular dysfunction has been proposed to precede atherosclerosis, and in addition, a correlation between vascular...... isolated from 8 week old male SD rats were cultured for 21 hours in Endothelial Basal Medium (EBM-2) in petri dishes and in the absence or presence of either 30 mM D-glucose, 100 nM insulin, 100 ng/mL TNFa or any combination of these. Contractile reactivity of normalised arteries was then determined...... by wire myography as a response to cumulatively increasing concentrations of noradrenaline (NA). Results: 21 hour culture of isolated mesenteric arteries significantly reduced the arteries maximal high potassium-induced contractile reactivity and increased the contractility to noradrenaline slightly...

  15. Role of catecholamines and nitric oxide on pigment displacement of the chromatophores of freshwater snakehead teleost fish, Channa punctatus.

    Science.gov (United States)

    Biswas, Saikat P; Jadhao, Arun G; Palande, Nikhil V

    2014-04-01

    We are reporting for the first time that the catecholamines (adrenaline and noradrenaline) inhibit the effect of nitric oxide (NO) on melanosome dispersion in freshly isolated scales of the freshwater snakehead fish, Channa punctatus. We studied the effect of NO and catecholamines on the pigment displacement by observing the changes in the melanophore index. The scales when treated with solution containing NO donor sodium nitroprusside (SNP) showed dispersion of melanosomes, whereas NO synthase blocker N-omega-Nitro-L-arginine suppresses this action of SNP. Treatment with adrenaline and noradrenaline on the isolated scales caused aggregation of melanosomes. Scales treated with solution containing catecholamines and SNP resulted in aggregation of melanosomes suggesting that catecholamines mask the effect of SNP. These results suggest that the catecholamines are inhibiting the effect of NO and causing the aggregation of the melanosomes may be via surface receptors.

  16. Action of (R)-sila-venlafaxine and reboxetine to antagonize cisplatin-induced acute and delayed emesis in the ferret

    International Nuclear Information System (INIS)

    Warneck, Julie B.; Cheng, Frankie H.M.; Barnes, Matthew J.; Mills, John S.; Montana, John G.; Naylor, Robert J.; Ngan, Man-P.; Wai, Man-K.; Daiss, Juergen O.; Tacke, Reinhold; Rudd, John A.

    2008-01-01

    The chemotherapeutic drug cisplatin is associated with severe gastrointestinal toxicity that can last for several days. A recent strategy to treat the nausea and emesis includes the combination of a 5-HT 3 receptor antagonist, a glucocorticoid, and an NK 1 receptor antagonist. The present studies explore the use of the selective noradrenaline reuptake inhibitors, (R)-sila-venlafaxine, (R,R)-reboxetine and (S,S)-reboxetine to prevent cisplatin (5 mg/kg, i.p.)-induced acute (0-24 h) and delayed (24-72 h) emesis in ferrets. The positive control regimen of ondansetron and dexamethasone, both at 1 mg/kg/8 h, reduced acute and delayed emesis by 100 (P 0.05). In conclusion, the studies provide the first evidence for an anti-emetic potential of noradrenaline reuptake inhibitors to reduce chemotherapy-induced acute and delayed emesis

  17. Bepaling van enkele neurotransmitters, monoaminen, en metabolieten, met behulp van Continuous Flowapparatuur

    NARCIS (Netherlands)

    Eigeman L; Schonewille F; Borst M; van der Laan JW

    1986-01-01

    Bij het onderzoek in de psychofarmacologie kan kennis van de effecten van stoffen op de omzettingssnelheid van neurotransmitters een belangrijk aspect zijn. Met de huidige psychofarmaca lijken vooral de klassieke neurotransmitters zoals de monoaminen, noradrenaline, dopamine en serotonine van

  18. Cerebral effects of commonly used vasopressor-inotropes

    DEFF Research Database (Denmark)

    Hahn, Gitte Holst; Hyttel-Sorensen, Simon; Petersen, Sandra Meinich

    2013-01-01

    Despite widespread use in sick infants, it is still debated whether vasopressor-inotropes have direct cerebral effects that might affect neurological outcome. We aimed to test direct cerebrovascular effects of three commonly used vasopressor-inotropes (adrenaline, dopamine and noradrenaline...

  19. Effects of chlordiazepoxide and buspirone on plasma catecholamine and corticosterone levels in rats under basal and stress conditions

    NARCIS (Netherlands)

    de Boer, S.F.; Slangen, J L; van der Gugten, J

    The effects of the classical benzodiazepine (BDZ) anxiolytic drug chlordiazepoxide (CDP) and the non-BDZ anxiolytic agent buspirone (BUSP) on basal and stress-induced plasma noradrenaline (NA), adrenaline (A) and corticosterone (CS) release were investigated. Male Wistar rats provided with a

  20. Physiological and psychological reactions to work in men and women with identical job tasks

    DEFF Research Database (Denmark)

    Persson, Roger; Hansen, Åse Marie; Ohlsson, Kerstina

    2009-01-01

    decrease in perceived energy levels during the workshift but there were no differences between men and women as regards cortisol, adrenaline, noradrenaline, heart-rate activation, perceived stress, pain and physical exertion. In conclusion, differential physiological activation during the workshift seem...

  1. Conversion of Short-Term Potentiation to Long-Term Potentiation in Mouse CA1 by Coactivation of [beta]-Adrenergic and Muscarinic Receptors

    Science.gov (United States)

    Connor, Steven A.; Maity, Sabyasachi; Roy, Birbickram; Ali, Declan W.; Nguyen, Peter V.

    2012-01-01

    Encoding new information requires dynamic changes in synaptic strength. The brain can boost synaptic plasticity through the secretion of neuromodulatory substances, including acetylcholine and noradrenaline. Considerable effort has focused on elucidating how neuromodulatory substances alter synaptic properties. However, determination of the…

  2. Distinct modulatory effects of satiety and sibutramine on brain responses to food images in humans: a double dissociation across hypothalamus, amygdala, and ventral striatum

    NARCIS (Netherlands)

    Fletcher, P.C.; Napolitano, A.; Skeggs, A.; Miller, S.R.; Delafont, B.; Cambridge, V.C.; de Wit, S.; Nathan, P.J.; Brooke, A.; O'Rahilly, S.; Farooqi, I.S.; Bullmore, E.T.

    2010-01-01

    We used functional magnetic resonance imaging to explore brain responses to food images in overweight humans, examining independently the impact of a prescan meal ("satiety") and the anti-obesity drug sibutramine, a serotonin and noradrenaline reuptake inhibitor. We identified significantly

  3. Atomoxetine effects on attentional bias to drug-related cues in cocaine dependent individuals

    NARCIS (Netherlands)

    Passamonti, L. (Luca); M. Luijten (Maartje); Ziauddeen, H.; I. Coyle-Gilchrist (Ian); Rittman, T.; Brain, S.A.E.; Regenthal, R.; I.H.A. Franken (Ingmar); Sahakian, B.J.; Bullmore, E.T.; Robbins, T.W.; Ersche, K.D.

    2017-01-01

    textabstractRationale: Biased attention towards drug-related cues and reduced inhibitory control over the regulation of drug-intake characterize drug addiction. The noradrenaline system has been critically implicated in both attentional and response inhibitory processes and is directly affected by

  4. Changes in Plasma Corticosterone and Catecholamine Contents Induced by Low Doses of Deltamethrin in Rats

    NARCIS (Netherlands)

    Boer, Sietse F. de; Gugten, Jan van der; Slangen, Jef. L.; Hijzen, Theo H.

    1988-01-01

    The effects of low doses of (S)-α-cyano-3-phenoxybenzyl (1R)-cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate (Roussel UCLAF, Paris, France), (deltamethrin) upon sympathetic-adrenomedullary and pituitary-adrenocortical activity were investigated in rats by measuring plasma noradrenaline

  5. GENetic and clinical Predictors Of treatment response in Depression: the GenPod randomised trial protocol

    Directory of Open Access Journals (Sweden)

    O'Donovan Michael

    2008-05-01

    Full Text Available Abstract Background The most effective pharmacological treatments for depression inhibit the transporters that reuptake serotonin (Selective Serotonin Reuptake Inhibitors – SSRIs and noradrenaline (Noradrenaline Reuptake Inhibitors – NaRIs into the presynaptic terminal. There is evidence to suggest that noradrenaline and serotonin enhancing drugs work through separate mechanisms to produce their clinical antidepressant action. Although most of the current evidence suggests there is little difference in overall efficacy between SSRIs and NaRIs, there are patients who respond to one class of compounds and not another. This suggests that treatment response could be predicted by genetic and/or clinical characteristics. Firstly, this study aims to investigate the influence of a polymorphism (SLC6A4 in the 5HT transporter in altering response to SSRI medication. Secondly, the study will investigate whether those with more severe depression have a better response to NaRIs than SSRIs. Methods/design The GenPod trial is a multi-centre randomised controlled trial. GPs referred patients aged between 18–74 years presenting with a new episode of depression, who did not have any medical contraindications to antidepressant medication and who had no history of psychosis or alcohol/substance abuse. Patients were interviewed to ascertain their suitability for the study. Eligible participants (with a primary diagnosis of depression according to ICD10 criteria and a Beck Depression Inventory (BDI score > 14 were randomised to receive one of two antidepressant treatments, either the SSRI Citalopram or the NaRI Reboxetine, stratified according to severity. The final number randomised to the trial was 601. Follow-up assessments took place at 2, 6 and 12 weeks following randomisation. Primary outcome was measured at 6 weeks by the BDI. Outcomes will be analysed on an intention-to-treat basis and will use multiple regression models to compare treatments

  6. Enhanced noradrenergic activity in the amygdala contributes to hyperarousal in an animal model of PTSD

    NARCIS (Netherlands)

    Ronzoni, G.; Arco, A. Del; Mora, F.; Segovia, G.

    2016-01-01

    Increased activity of the noradrenergic system in the amygdala has been suggested to contribute to the hyperarousal symptoms associated with post-traumatic stress disorder (PTSD). However, only two studies have examined the content of noradrenaline or its metabolites in the amygdala of rats

  7. Study of plasma amino acid levels in children with autism: An ...

    African Journals Online (AJOL)

    Background: The aetiology of autism is unclear and autistic symptoms had been attributed to an abnormal functional imbalance in neurotransmitter amines such as dopamine, noradrenaline and serotonin. Objective: To study plasma essential and non-essential amino acid levels, protein electrophoresis, serum ammonia, ...

  8. Sympathoadrenal Activation and Endothelial Damage Are Inter Correlated and Predict Increased Mortality in Patients Resuscitated after Out-Of-Hospital Cardiac Arrest

    DEFF Research Database (Denmark)

    I. Johansson, Pär; Bro-Jeppesen, John; Kjaergaard, Jesper

    2015-01-01

    site ICU. Blood was sampled a median 135 min (Inter Quartile Range (IQR) 103-169) after OHCA. Plasma catecholamines (adrenaline, noradrenaline) and serum endothelial biomarkers (syndecan-1, thrombomodulin, sE-selectin, sVE-cadherin) were measured at admission (immediately after randomization). We had...

  9. Amine metabolism in the human brain : evaluation of the probenecid test

    NARCIS (Netherlands)

    Korf, Jacob

    1971-01-01

    There are indirect indications, that biogenic amines in the brain are concerned with pathological states such as depression (serotonin, 5HT and noradrenaline, NA) and Parkonsonism (dopamine, DA). These indications were obtained from measurements of amines and their metabolites in pe - ripheral

  10. Acute Stressor Effects on Goal-Directed Action in Rats

    Science.gov (United States)

    Braun, Stephanie; Hauber, Wolfgang

    2013-01-01

    Here we examined effects of acute stressors that involve either systemic coadministration of corticosterone/yohimbine (3 mg/kg each) to increase glucocorticoid/noradrenaline activity (denoted as "pharmacological" stressor) or one or several distinct restraint stressors (denoted as "single" vs. "multiple" stressor) on…

  11. Modulatory effects of defense and coping on stress-induced changes in endocrine and immune parameters

    NARCIS (Netherlands)

    Olff, M.; Brosschot, J. F.; Godaert, G.; Benschop, R. J.; Ballieux, R. E.; Heijnen, C. J.; de Smet, M. B.; Ursin, H.

    1995-01-01

    We examined whether habitual defense and coping affect the response of hormones (ACTH. cortisol, prolactin. endorphins, and noradrenaline) and immune parameters (numbers of T cells. B cells. natural killer [NK] cells, and proliferative responses to mitogens or antigens) to an acute laboratory

  12. Interacting noradrenergic and corticosteroid systems shift human brain activation patterns during encoding

    NARCIS (Netherlands)

    van Stegeren, Anda H.; Roozendaal, Benno; Kindt, Merel; Wolf, Oliver T.; Joëls, Marian

    Emotionally arousing experiences are usually well retained, an effect that depends on the release of adrenal stress hormones. Animal studies have shown that corticosterone and noradrenaline - representing the two main stress hormone systems - act in concert to enhance memory formation by actions

  13. Interacting noradrenergic and corticosteroid systems shift human brain activation patterns during encoding

    NARCIS (Netherlands)

    van Stegeren, A.H.; Roozendaal, B.; Kindt, M.; Wolf, O.T.; Joëls, M.

    2010-01-01

    Emotionally arousing experiences are usually well retained, an effect that depends on the release of adrenal stress hormones. Animal studies have shown that corticosterone and noradrenaline - representing the two main stress hormone systems - act in concert to enhance memory formation by actions

  14. Nicotine, but not mecamylamine, enhances antidepressant-like effects of citalopram and reboxetine in the mouse forced swim and tail suspension tests

    DEFF Research Database (Denmark)

    Andreasen T., Jesper; Redrobe, John P

    2009-01-01

    and 10mg/kg citalopram and 3 and 10mg/kg reboxetine in the mTST. No concomitant locomotor stimulation was observed at the tested dose combinations. Mecamylamine was effective on its own in some tests, but did not augment the effects of citalopram or reboxetine at the doses tested. The data show...... activity and facilitates serotonin and noradrenaline release. Thus, we hypothesise that nicotine may enhance the behavioural effects of serotonin (e.g., citalopram) and/or noradrenaline (e.g., reboxetine) reuptake inhibitors. Here, we tested if nicotine enhanced the activity of citalopram or reboxetine...... in the mouse forced swim test (mFST) and the mouse tail suspension test (mTST). The potential for mecamylamine to augment antidepressant drug action was also investigated. Sub-threshold and threshold doses of citalopram (3 and 10mg/kg) or reboxetine (3, 10 and 20mg/kg) were tested alone and in combination...

  15. Effect of venlafaxine hydrochloride in different preparations of isolated guinea-pig and rat organ tissues.

    Science.gov (United States)

    Velasco, A; Arruza, A; Maroto, M; Carvajal, A; Fernández del Busto, E; García del Pozo, J

    1999-04-01

    A study was undertaken to know better the effects of venlafaxine hydrochloride on the responses of isolated rat vas deferens to noradrenaline and dopamine, those of isolated rat uterus to serotonin and histamine, and those of isolated guinea-pig ileum to acetylcholine and histamine. Venlafaxine hydrochloride increased the response of rat vas deferens to noradrenaline but not to dopamine. Venlafaxine did not alter the response of rat isolated uterus to serotonin. In rat uterus, venlafaxine did not modify the response to histamine but was able to increase it in guinea-pig ileum. An anticholinergic effect was observed with the lowest concentration tested. Although venlafaxine is a selective serotonine reuptake inhibitor in the central nervous system, serotonin uptake was not seen in the rat uterus. The anticholinergic effects observed in the present study might be consistent with some of the side-effects associated with venlafaxine.

  16. Heart rate response to hypoxic exercise

    DEFF Research Database (Denmark)

    Lundby, C; Møller, P; Kanstrup, I L

    2001-01-01

    progressively decreased the maximal heart rate from day 1 and onwards; also, hypoxia by itself increased plasma noradrenaline levels after maximal exercise. Domperidone further increased maximal noradrenaline concentrations, but had no effect on maximal heart rate. On each study day at altitude, oxygen......This study examined the effects of dopamine D(2)-receptor blockade on the early decrease in maximal heart rate at high altitude (4559 m). We also attempted to clarify the time-dependent component of this reduction and the extent to which it is reversed by oxygen breathing. Twelve subjects performed...... two consecutive maximal exercise tests, without and with oxygen supplementation respectively, at sea level and after 1, 3 and 5 days at altitude. On each study day, domperidone (30 mg; n=6) or no medication (n=6) was given 1 h before the first exercise session. Compared with sea level, hypoxia...

  17. Synthesis of organic substances labelled with {sup 14}C and {sup 35}S; Syntheses de molecules organiques marquees par le carbone-14 et le soufre-35

    Energy Technology Data Exchange (ETDEWEB)

    Pichat, L [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1958-07-01

    After a brief history of the development of the Section des Molecules marquees of the Frenchmic Energy Commission, the author gives an outline of the synthesis of the following labelled compounds: benzene {sup 14}C-6; phenyl-p-fluorophenyl, thienyl-2 {beta} alanines {beta} {sup 14}C; noradrenaline {beta} {sup 14}C (arterenol {beta} {sup 14}C), dotriacontane {sup 14}C-16-17, aminoethane sulfinic acid (hypotaurine {sup 35}S). (author)Fren. [French] Apres un bref historique du developpement de la Section des Molecules marquees du Commissariat a l'Energie Atomique fran is, l'auteur donne un resume des syntheses des composes marques suivants: benzene {sup 14}C-6; phenyl-p-fluorophenyl, thienyl-2 {beta} alamines {beta} {sup 14}C; noradrenaline {beta} {sup 14}C (arterenol {beta} {sup 14}C), dotriacontane {sup 14}C-16-17, acide aminoethane sulfinique (hypotaurine {sup 35}S). (auteur)

  18. The importance of neurotransmitters in the central control of the blood pressure

    International Nuclear Information System (INIS)

    Pfitscher-Klausmair, A.

    1990-12-01

    In anaesthetized cats, the nucleus tractus solitarii (NTS) and the locus coeruleus (LC) were bilaterally superfused through push-pull cannulae with artificial cerebrospinal fluid. Catecholamines were determined in the superfusate by a radioenzymatic assay, gamma-aminobutyric acid (GABA) was determined in the superfusate and homogenate with glutamate by an enzymatic and fluorimetric assay. In the NTS and LC the resting release of catecholamines varied rhythmically. To investigate the function of catecholaminergic neurons and GABAergic neurons of the NTS in cardiovascular control, the influence of experimentally induced blood pressure changes on the rates of release of the endogenous catecholamines dopamine, noradrenaline and adrenaline in the NTS was observed. The decreased noradrenaline and adrenaline release elicited by increases in blood pressure and the reduced release of dopamine induced by decreases in blood pressure suggest a hypertensive function of noradrenaline and adrenaline and a hypotensive role of dopamine at the level of the rostral and intermediate NTS. Bilateral carotid occlusion led to a very pronounced increase in the release rate of GABA in the rostral NTS. This result demonstrate the hypertensive function of GABA in the NTS. Thus underlining the importance of catecholaminergic and GABAergic neurons of the NTS in central cardiovascular control. The GABA-transaminase inhibitor Vigabatrin was injected wistar Kyoto rats and spontaneously hypertensive rats. GABA-Transaminase inhibition was accompanied by an increase of GABA concentration in the rat brain. The administration of Vigabatrin had no influence on the blood pressure but on the body wight of the rats. (Author)

  19. Cardiac iodine-123 metaiodobenzylguanidine uptake in animals with diabetes mellitus and/or hypertension

    International Nuclear Information System (INIS)

    Dubois, E.A.; Kam, K.L.; Somsen, G.A.; Boer, G.J.; Bruin, K. de; Batink, H.D.; Pfaffendorf, M.; Royen, E.A. van; Zwieten, P.A. van

    1996-01-01

    The aim of the present study was to evaluate the use of the noradrenaline analogue iodine-123 metaiodobenzylguanidine ([ 123 I]MIBG) for the assessment of cardiac sympathetic activity in the presence of diabetes mellitus and/or hypertension in animal models. One model used Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) rendered diabetic at 12 weeks of age by an intravenous injection of streptozotocin (STZ). The other model used lean and obese Zucker rats. In all groups basic haemodynamic values were established and animals received an intravenous injection of 50 μCi [ 123 I]MIBG. Initial myocardial uptake and washout rates of [ 123 I]MIBG were measured scintigraphically during 4 h. After sacrifice, plasma noradrenaline and left cardiac ventricular β-adrenoceptor density was determined. The diabetic state, both in STZ-treated rats (direct induction) and in obese Zucker rats (genetic induction), appeared to induce a lower cardiac density of β-adrenoceptors, indicative of increased sympathetic activity. Cardiac [ 123 I]MIBG then showed increased washouts, thereby confirming enhanced noradrenergic activity. This parallism of results led to the conclusion that [ 123 I]MIBG wash-out measurements could provide an excellent tool to assess cardiac sympathetic activity noninvasively. However, in hypertension (WKY vs SHR), both parameters failed to show parallelism: no changes in β-adrenoceptor density were found, whereas [ 123 I]MIBG wash-out rate was increased. Thus, either [ 123 I]MIBG washout or β-adrenoceptor density may not be a reliable parameter under all circumstances to detect changes in the release of noradrenaline. (orig./MG)

  20. Potentiation by substance P of contractions of the isolated vas deferens of the mouse elicited by electric field stimulation and by drugs

    International Nuclear Information System (INIS)

    Blackwell, M.; James, T.A.; Starr, M.S.

    1978-01-01

    Isolated vasa deferentia from the mouse were opened longitudinally and suspended in Krebs solution at 37 0 C in an organ bath. Contractions of the muscle were elicited by electric field stimulation, noradrenaline (10 -6 M) and acetylcholine (10 -6 M). Continued transmural stimulation evoked a biphasic response comprising a rapid twitch followed by about 10 s later by a smaller, sustained rise in muscle tone. The amplitudes of nerve-mediated and drug-induced responses were considerably potentiated by substances P (SP) in the dose range 10 -12 to 10 -7 M. Higher concentrations of SP were directly spasmogenic. The sensitizing property of SP was dose-dependent and was usually well maintained, but always disappeared quickly on washing the preparation. In some experiments SP facilitated the twitch, but not the subsequent phase of the electrically-induced contraction or the response to externally applied noradrenaline. Phentolamine (10 -6 M) failed to block this effect of SP, but itself potentiated the nerve-mediated twitch, and completely abolished the sustained secondary contraction. Desmethylimipramine (10 -6 M) enhanced the delayed contraction but not the immediate contraction. The uptake of tritiated noradrenaline (3 x 10 -7 M) by vasa was inhibited by desmethylimipramine (10 -6 M) and increased by nialamide (3 x 10 -5 M), but was not modified by SP (10 -6 M). Nerve-mediated release of accumulated radioactivity was accelerated by phentolamine, but not by SP or desmethylimipramine. These findings suggest that SP sensitizes the muscle cells to depolarizing stimuli but that it has no facilitatory effect on sympathetic neural elements. (author)

  1. Monoamine involvement in the antidepressant-like effect induced by P2 blockade.

    Science.gov (United States)

    Diniz, Cassiano R A F; Rodrigues, Murilo; Casarotto, Plínio C; Pereira, Vítor S; Crestani, Carlos C; Joca, Sâmia R L

    2017-12-01

    Depression is a common mental disorder that affects millions of individuals worldwide. Available monoaminergic antidepressants are far from ideal since they show delayed onset of action and are ineffective in approximately 40% of patients, thus indicating the need of new and more effective drugs. ATP signaling through P2 receptors seems to play an important role in neuropathological mechanisms involved in depression, since their pharmacological or genetic inactivation induce antidepressant-like effects in the forced swimming test (FST). However, the mechanisms involved in these effects are not completely understood. The present work investigated monoamine involvement in the antidepressant-like effect induced by non-specific P2 receptor antagonist (PPADS) administration. First, the effects of combining sub-effective doses of PPADS with sub-effective doses of fluoxetine (FLX, selective serotonin reuptake inhibitor) or reboxetine (RBX, selective noradrenaline reuptake inhibitor) were investigated in mice submitted to FST. Significant antidepressant-like effect was observed when subeffective doses of PPADS was combined with subeffective doses of either FLX or RBX, with no significant locomotor changes. Next, the effects of depleting serotonin and noradrenaline levels, by means of PCPA (p-Chlorophenylalanine) or DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride) pretreatment, respectively, was investigated. Both, PCPA and DSP-4 pretreatment partially attenuated PPADS-induced effects in FST, without inducing relevant locomotor changes. Our results suggest that the antidepressant-like effect of PPADS involves modulation of serotonin and noradrenaline levels in the brain. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Endothelial and Neuronal Nitric Oxide Activate Distinct Pathways on Sympathetic Neurotransmission in Rat Tail and Mesenteric Arteries.

    Directory of Open Access Journals (Sweden)

    Joana Beatriz Sousa

    Full Text Available Nitric oxide (NO seems to contribute to vascular homeostasis regulating neurotransmission. This work aimed at assessing the influence of NO from different sources and respective intracellular pathways on sympathetic neurotransmission, in two vascular beds. Electrically-evoked [3H]-noradrenaline release was assessed in rat mesenteric and tail arteries in the presence of NO donors or endothelial/neuronal nitric oxide synthase (NOS inhibitors. The influence of NO on adenosine-mediated effects was also studied using selective antagonists for adenosine receptors subtypes. Location of neuronal NOS (nNOS was investigated by immunohistochemistry (with specific antibodies for nNOS and for Schwann cells and Confocal Microscopy. Results indicated that: 1 in mesenteric arteries, noradrenaline release was reduced by NO donors and it was increased by nNOS inhibitors; the effect of NO donors was only abolished by the adenosine A1 receptors antagonist; 2 in tail arteries, noradrenaline release was increased by NO donors and it was reduced by eNOS inhibitors; adenosine receptors antagonists were devoid of effect; 3 confocal microscopy showed nNOS staining in adventitial cells, some co-localized with Schwann cells. nNOS staining and its co-localization with Schwann cells were significantly lower in tail compared to mesenteric arteries. In conclusion, in mesenteric arteries, nNOS, mainly located in Schwann cells, seems to be the main source of NO influencing perivascular sympathetic neurotransmission with an inhibitory effect, mediated by adenosine A1 receptors activation. Instead, in tail arteries endothelial NO seems to play a more relevant role and has a facilitatory effect, independent of adenosine receptors activation.

  3. Mechanisms of isoform-specific Na/K pump regulation by short- and long-term adrenergic activation in rat ventricular myocytes.

    Science.gov (United States)

    Yin, Jian; Guo, Hui-Cai; Yu, Ding; Wang, Hui-Ci; Li, Jun-Xia; Wang, Yong-Li

    2014-01-01

    Many stressful conditions, including cardiovascular diseases, induce long-term elevations in circulating catecholamines, thereby leading to changes of the Na/K pump and thus affecting myocardial functions. However, only short-term adrenergic regulation of the Na/K pump has been reported. The present study is the first investigation of long-term adrenergic regulation of the Na/K pump and the potential mechanism. After acutely isolated Sprague-Dawley rat myocytes were incubated with noradrenaline or isoprenaline for 24 h, Na/K pump high- (IPH) and low-affinity current (IPL), α-isoform mRNA, and α-isoform protein were examined using patch-clamp, RT-PCR, and Western blotting techniques, respectively. After the short-term incubation, isoprenaline reduced the IPL through a PKA-dependent pathway that involves α1-isoform translocation from the membrane to early endosomes, and noradrenaline increased the IPH through a PKC-dependent pathway that involves α2-isoform translocation from late endosomes to the membrane. After long-term incubation, isoprenaline increased the IPL, α1-isoform mRNA, and α1-isoform protein, and noradrenaline reduced the IPH, α2-isoform mRNA, and α1-isoform protein through a PKA-or PKC-dependent pathway, respectively. These results suggest that long-term adrenergic Na/K pump regulation is isoform-specific and negatively feeds back on the short-term response. Furthermore, long-term regulation involves transcription and translation of the respective α-isoform, whereas short-term regulation involves the translocation of the available α-isoform to the plasma membrane. © 2014 S. Karger AG, Basel.

  4. Mechanisms of Isoform-Specific Na/K Pump Regulation by Short- and Long-Term Adrenergic Activation in Rat Ventricular Myocytes

    Directory of Open Access Journals (Sweden)

    Jian Yin

    2014-05-01

    Full Text Available Background: Many stressful conditions, including cardiovascular diseases, induce long-term elevations in circulating catecholamines, thereby leading to changes of the Na/K pump and thus affecting myocardial functions. However, only short-term adrenergic regulation of the Na/K pump has been reported. The present study is the first investigation of long-term adrenergic regulation of the Na/K pump and the potential mechanism. Methods: After acutely isolated Sprague-Dawley rat myocytes were incubated with noradrenaline or isoprenaline for 24 h, Na/K pump high- (IPH and low-affinity current (IPL, α-isoform mRNA, and α-isoform protein were examined using patch-clamp, RT-PCR, and Western blotting techniques, respectively. Results: After the short-term incubation, isoprenaline reduced the IPL through a PKA-dependent pathway that involves α1-isoform translocation from the membrane to early endosomes, and noradrenaline increased the IPH through a PKC-dependent pathway that involves α2-isoform translocation from late endosomes to the membrane. After long-term incubation, isoprenaline increased the IPL, α1-isoform mRNA, and α1-isoform protein, and noradrenaline reduced the IPH, α2-isoform mRNA, and α1-isoform protein through a PKA-or PKC-dependent pathway, respectively. Conclusions: These results suggest that long-term adrenergic Na/K pump regulation is isoform-specific and negatively feeds back on the short-term response. Furthermore, long-term regulation involves transcription and translation of the respective α-isoform, whereas short-term regulation involves the translocation of the available α-isoform to the plasma membrane.

  5. Plasma catecholamine and corticosterone responses to predictable and unpredictable noise stress in rats

    NARCIS (Netherlands)

    Van der Gugten, J; Slangen, J L; de Boer, S.F.

    Plasma noradrenaline (NA), adrenaline (A) and corticosterone (CS) increases were determined in individual rats subjected to either 20 regularly or irregularly scheduled white-noise stimulations (4 min, 100 dBA). Blood was frequently sampled during the first and twentieth noise exposure, and during a

  6. Amines, Astrocytes and Arousal

    OpenAIRE

    Bazargani, N.; Attwell, D.

    2017-01-01

    Amine neurotransmitters, such as noradrenaline, mediate arousal, attention, and reward in the CNS. New data suggest that, from flies to mammals, a major mechanism for amine transmitter action is to raise astrocyte [Ca2+]i and release gliotransmitters that modulate neuronal activity and behavior.

  7. Alpha 1A and alpha 1B-adrenoceptors enhance inositol phosphate generation in rat renal cortex

    NARCIS (Netherlands)

    Michel, M. C.; Büscher, R.; Philipp, T.; Brodde, O. E.

    1993-01-01

    We have studied the role of alpha 1A- and alpha 1B-adrenoceptors in noradrenaline- and methoxamine-stimulated inositol phosphate accumulation in rat renal cortical slices. [3H]Prazosin binding studies with and without inactivation of alpha 1B-adrenoceptors by chloroethylclonidine treatment suggested

  8. Inverse agonism at α2A adrenoceptors augments the hypophagic effect of sibutramine in rats

    NARCIS (Netherlands)

    Janhunen, Sanna K.; van der Zwaal, Esther M.; la Fleur, Susanne E.; Adan, Roger A. H.

    2011-01-01

    Because the use of monoamine reuptake inhibitors as weight-reducing agents is limited by adverse effects, novel antiobesity drugs are needed. We studied acute effects of the noradrenaline (NA) and serotonin (5-HT) reuptake inhibitor sibutramine (SIB), alone and after pretreatment with α1- and

  9. Effects of fasting on plasma catecholamine, corticosterone and glucose concentrations under basal and stress conditions in individual rats

    NARCIS (Netherlands)

    de Boer, S.F.; Koopmans, S.J.; Slangen, J L; Van der Gugten, J

    Plasma noradrenaline (NA), adrenaline (A), corticosterone (CS) and glucose concentrations were determined in blood sampled via a cardiac catheter from freely moving male rats under ad lib fed and 24 hr food deprived conditions using a repeated measures within-subject design. Resting plasma NA and

  10. Ameliorative Effects of Neurolytic Celiac Plexus Block on Stress and ...

    African Journals Online (AJOL)

    Purpose: To investigate effects of neurolytic celiac plexus block (NCPB) on stress and inflammation in rats with partial hepatectomy (PH). Methods: A model of PH rat was established, and serum C-reactive protein (CRP); corticosterone (GC); adrenocorticotropin (ACTH); noradrenaline (NA); adrenalin (AD); aspartate ...

  11. Neurotoxic effect of maneb in rats as studied by neurochemical and immunohistochemical parameters

    DEFF Research Database (Denmark)

    Nielsen, Brian Svend; Larsen, Erik Huusfeldt; Ladefoged, Ole

    2006-01-01

    ) increased in a dose-related manner, as did the 5-HT concentrations in the rest of the brain indicating early sign of neurotoxicity. Striatal acetylcholinesterase activity was not affected. The concentrations of noradrenaline, dopamine, neurotransmitter amino acids and the levels of the proteins alpha...

  12. Beta-adrenergic control of plasma glucose and free fatty acid levels in the air-breathing African catfish Clarias gariepinus Burchell 1822

    NARCIS (Netherlands)

    van Heeswijk, JCF; Vianen, GJ; van den Thillart, GEEJM; Zaagsma, J

    In several water-breathing fish species, P-adrenergic receptor stimulation by noradrenaline leads to a decrease in plasma free fatty acid (FFA) levels, as opposed to an increase in air-breathing mammals. We hypothesised that this change in adrenergic control is related to the mode of breathing.

  13. Alpha 1 B- but not alpha 1 A-adrenoceptors mediate inositol phosphate generation

    NARCIS (Netherlands)

    Michel, M. C.; Hanft, G.; Gross, G.

    1990-01-01

    We used novel highly subtype-selective antagonists to study whether alpha 1A- and/or alpha 1B-adrenoceptors mediate the stimulation of inositol phosphate generation by noradrenaline in rat cerebral cortex. Phentolamine (10 microM) and prazosin (100 nM) completely abolished the stimulated inositol

  14. Autonomic response to an experimental psychological stressor in healthy subjects: measurement of sympathetic, parasympathetic, and pituitary-adrenal parameters: test-retest reliability

    DEFF Research Database (Denmark)

    Jørgensen, L S; Christiansen, P; Raundahl, U

    1990-01-01

    A mental arithmetic test (the stressor; 15 min) significantly increased systolic and diastolic blood pressure, heart rate and plasma adrenaline by 11%, 12%, 28% and 152% respectively, with a prompt return to resting values after the test. Plasma noradrenaline and serum cortisol did not increase s...

  15. Catecholaminergic development of fetal rat ventral mesencephalon : Characterization by high-performance liquid chromatography with electrochemical detection and immunohistochemistry

    NARCIS (Netherlands)

    Tomasini, R; Kema, IP; Muskiet, FAJ; Meiborg, G; Staal, MJ; Go, KG

    We determined dopamine (DA), noradrenaline (NA), and adrenaline (A), as well as immunohistochemically stained tyrosine hydroxylase (TH) and DA in dissected rat ventral mesencephalon (VM) tissue from Embryonic Day (ED) 14 to Postnatal Day (P) 17. Whole VM tissue DA, NA, and A contents increased with

  16. A computational psychiatry approach identifies how alpha-2a noradrenergic agonist guanfacine affects feature-based reinforcement learning in the macaque

    NARCIS (Netherlands)

    Hassani, S.A.; Oemisch, M.; Balcarras, M.; Westendorff, S.; Ardid, S.; van der Meer, M.A.; Tiesinga, P.H.E.; Womelsdorf, T.

    2017-01-01

    Noradrenaline is believed to support cognitive flexibility through the alpha 2A noradrenergic receptor (a2A-NAR) acting in prefrontal cortex. Enhanced flexibility has been inferred from improved working memory with the a2A-NA agonist Guanfacine. But it has been unclear whether Guanfacine improves

  17. Blueberry juice causes potent relaxation of rat aortic rings via the activation of potassium channels and the H₂S pathway.

    Science.gov (United States)

    Horrigan, Louise A; Holohan, Catherine A; Lawless, Gráinne A; Murtagh, Melissa A; Williams, Carmel T; Webster, Christina M

    2013-02-26

    The objective of this study was to investigate the in vitro effects of blueberry juice on healthy rat aortic rings, and to explore the roles of potassium channels and of the hydrogen sulphide (H(2)S) pathway in mediating the effects of blueberry juice. Firstly, the antioxidant capacity of blueberry juice was compared to other popular juice drinks using the Folin-Ciocalteu and the DPPH assays. Blueberry juice had significantly higher total polyphenol content than any of the other drinks studied (p blueberry juice on noradrenaline-contracted aortic rings was then observed, and the juice caused significant inhibition of noradrenaline-induced contractions (p blueberry juice (p blueberry juice (p blueberry juice has potent vasorelaxing properties, and thus may be a useful dietary agent for the prevention and treatment of hypertension. This study also provides strong evidence that Kv channels and the CSE/H(2)S pathway may be responsible, at least in part, for mediating the effects of blueberry juice.

  18. Alpha 2B adrenoceptor genotype moderates effect of reboxetine on negative emotional memory bias in healthy volunteers.

    Science.gov (United States)

    Gibbs, Ayana A; Bautista, Carla E; Mowlem, Florence D; Naudts, Kris H; Duka, Theodora

    2013-10-23

    Evidence suggests that emotional memory plays a role in the pathophysiology of depression/anxiety disorders. Noradrenaline crucially modulates emotional memory. Genetic variants involved in noradrenergic signaling contribute to individual differences in emotional memory and vulnerability to psychopathology. A functional deletion polymorphism in the α-2B adrenoceptor gene (ADRA2B) has been linked to emotional memory and post-traumatic stress disorder. The noradrenaline reuptake inhibitor reboxetine attenuates enhanced memory for negative stimuli in healthy and depressed individuals. We examined whether the effect of reboxetine on emotional memory in healthy individuals would be moderated by ADRA2B genotype. ADRA2B deletion carriers demonstrated enhanced emotional memory for negative stimuli compared with deletion noncarriers, consistent with prior studies. Reboxetine attenuated enhanced memory for negative stimuli in deletion noncarriers but had no significant effect in deletion carriers. This is the first demonstration of genetic variation influencing antidepressant drug effects on emotional processing in healthy humans.

  19. The importance of the time of digitalization for the incidence of spasms evoked by ouabain in strips of human saphenous vein.

    Science.gov (United States)

    Zerkowski, H R; Wagner, J

    1982-10-01

    The extent of contracture induced by ouabain on preparations of the greater saphenous vein obtained from patients undergoing elective coronary bypass surgery was investigated. The medical pretreatment of the various donor patients was similar but differed with regard to the duration of preoperative digitalization ranging from several days to months. Whereas the maximal contraction induced by noradrenaline was not influenced by prior digitalization, the contracture evoked by ouabain showed a strong dependency on the duration of preoperative digitalization. In patients without or with only short-term preoperative digitalization the spasm exerted by ouabain amounted to 48.8% and 49.2%, respectively, of the maximal contraction induced by noradrenaline, and decreased to zero in patients with long-term digitalization. From this result it is concluded that, in patients after coronary artery bypass grafting who did not receive cardiac glycosides for long-term treatment, the acute administration of glycosides may be a mechanism responsible for the early occlusion of saphenous vein bypass grafts.

  20. Astrocytic β2-adrenergic receptors mediate hippocampal long-term memory consolidation

    KAUST Repository

    Gao, Virginia; Suzuki, Akinobu; Magistretti, Pierre J.; Lengacher, Sylvain; Pollonini, Gabriella; Steinman, Michael Q.; Alberini, Cristina M.

    2016-01-01

    Emotionally relevant experiences form strong and long-lasting memories by critically engaging the stress hormone/neurotransmitter noradrenaline, which mediates and modulates the consolidation of these memories. Noradrenaline acts through adrenergic receptors (ARs), of which β2- Adrenergic receptors (βARs) are of particular importance. The differential anatomical and cellular distribution of βAR subtypes in the brain suggests that they play distinct roles in memory processing, although much about their specific contributions and mechanisms of action remains to be understood. Here we show that astrocytic rather than neuronal β2ARs in the hippocampus play a key role in the consolidation of a fear-based contextual memory. These hippocampal β2ARs, but not β1ARs, are coupled to the training-dependent release of lactate from astrocytes, which is necessary for long- Term memory formation and for underlying molecular changes. This key metabolic role of astrocytic β2ARs may represent a novel target mechanism for stress-related psychopathologies and neurodegeneration.

  1. Effects of catecholamines on rat myocardial metabolism. I. Influence of catecholamines on energy-rich nucleotides and phosphorylated fraction contents.

    Science.gov (United States)

    Merouze, P; Gaudemer, Y

    1975-01-01

    1. The influence of catecholamines (adrenaline and noradrenaline) on energy metabolism of the rat myocardium has been studied by incubating slices of this tissue with these hormones and by following the levels of the different phosphorylated fractions and adenylic nucleotides. 2. Similar effects are obtained with both hormones, adrenaline being more effective. 3. Catecholamines decrease significantly the total amount of phosphate while Pi content increases during the first 10 minutes of incubation; labile and residual phosphate contents increase at the beginning of incubation and decrease to the initial values afterwards. 4. ATP and ADP levels decrease significantly with both hormones; however, the effect of noradrenalin on the ATP level needs a longer time of incubation. The ATP/ADP ratios decrease after 5 minutes incubation and the total adenylic nucleotide content is severely decreased (35 per cent with adrenalin, after 20 minutes incubation). 5. Similar results have been obtained with other tissues; these results can explain the decrease of aerobic metabolism we observed under the same conditions.

  2. Astrocytic β2-adrenergic receptors mediate hippocampal long-term memory consolidation

    KAUST Repository

    Gao, Virginia

    2016-07-12

    Emotionally relevant experiences form strong and long-lasting memories by critically engaging the stress hormone/neurotransmitter noradrenaline, which mediates and modulates the consolidation of these memories. Noradrenaline acts through adrenergic receptors (ARs), of which β2- Adrenergic receptors (βARs) are of particular importance. The differential anatomical and cellular distribution of βAR subtypes in the brain suggests that they play distinct roles in memory processing, although much about their specific contributions and mechanisms of action remains to be understood. Here we show that astrocytic rather than neuronal β2ARs in the hippocampus play a key role in the consolidation of a fear-based contextual memory. These hippocampal β2ARs, but not β1ARs, are coupled to the training-dependent release of lactate from astrocytes, which is necessary for long- Term memory formation and for underlying molecular changes. This key metabolic role of astrocytic β2ARs may represent a novel target mechanism for stress-related psychopathologies and neurodegeneration.

  3. The cAMP cascade modulates the neuroinformative impact of quantal release at cholinergic synapse

    Czech Academy of Sciences Publication Activity Database

    Vyskočil, František; Bukcharaeva, E.; Samigullin, D. V.; Nikolsky, E. E.

    2001-01-01

    Roč. 2, č. 2 (2001), s. 317-323 ISSN 1539-2791 R&D Projects: GA AV ČR IAA7011902 Grant - others:EU(XX) Nesting; RFBR(RU) 99-04-48286 Institutional research plan: CEZ:AV0Z5011922 Keywords : frog neuromuscular synapse * noradrenaline Subject RIV: ED - Physiology

  4. Nigerian Quarterly Journal of Hospital Medicine - Vol 18, No 2 (2008)

    African Journals Online (AJOL)

    Artesunate causes relaxation of rat aortic rings and reduces the contractile response to noradrenaline · EMAIL FULL TEXT EMAIL FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. OA Sofola, I Raji, C Ladipo, HAB Coker. http://dx.doi.org/10.4314/nqjhm.v18i2.44976 ...

  5. Enhanced Noradrenergic Activity Potentiates Fear Memory Consolidation and Reconsolidation by Differentially Recruiting alpha1- and beta-Adrenergic Receptors

    Science.gov (United States)

    Gazarini, Lucas; Stern, Cristina A. Jark; Carobrez, Antonio P.; Bertoglio, Leandro J.

    2013-01-01

    Consolidation and reconsolidation are phases of memory stabilization that diverge slightly. Noradrenaline is known to influence both processes, but the relative contribution of alpha1- and beta-adrenoceptors is unclear. The present study sought to investigate this matter by comparing their recruitment to consolidate and/or reconsolidate a…

  6. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial

    DEFF Research Database (Denmark)

    Astrup, Arne; Madsbad, Sten; Breum, Leif

    2008-01-01

    BACKGROUND: Weight-loss drugs produce an additional mean weight loss of only 3-5 kg above that of diet and placebo over 6 months, and more effective pharmacotherapy of obesity is needed. We assessed the efficacy and safety of tesofensine-an inhibitor of the presynaptic uptake of noradrenaline...

  7. The influences of ionic concentrations and the intervals between ...

    African Journals Online (AJOL)

    The effect of pre-exposure ("priming") of vascular smooth muscle to different levels of calcium concentrations before the construction of the normal concentration - response curves (CRCs) in different calcium concentrations, was investigated. The results showed that when the rat tail artery was primed with 3μM noradrenaline ...

  8. Effect of serotonin receptor blockade on endocrine and cardiovascular responses to head-up tilt in humans

    DEFF Research Database (Denmark)

    Matzen, S; Secher, N H; Knigge, U

    1993-01-01

    ) and sympathetic activity (plasma noradrenaline; NA). A moderate increase in pituitary-adrenal hormones (plasma ACTH, beta-END and cortisol) was observed. After a mean tilt time of 30 +/- 5 min (n = 20) presyncopal symptoms associated with decreases in HR, TPR and arterial pressure occurred. At this time pituitary...

  9. Strong activation of vascular prejunctional beta 2-adrenoceptors in freely moving rats by adrenaline released as a co-transmitter

    NARCIS (Netherlands)

    COPPES, RP; SMIT, J; KHALI, NN; Brouwer, F.; ZAAGSMA, J

    1993-01-01

    The effect of adrenaline on the electrically evoked noradrenaline overflow in the portal vein of adrenal demedullated freely moving rats was studied. Adrenaline (100 ng/min) was infused for 2 h into the portal vein. After a 1-h interval when plasma adrenaline had returned to pre-infusion

  10. Light-controlled relaxation of the rat penile corpus cavernosum using NOBL-1, a novel nitric oxide releaser

    Directory of Open Access Journals (Sweden)

    Yuji Hotta

    2016-05-01

    Full Text Available Purpose: To investigate whether relaxation of the rat penile corpus cavernosum could be controlled with NOBL-1, a novel, lightcontrollable nitric oxide (NO releaser. Materials and Methods: Fifteen-week-old male Wistar-ST rats were used. The penile corpus cavernosum was prepared and used in an isometric tension study. After noradrenaline (10−5 M achieved precontraction, the penile corpus cavernosum was irradiated by light (470–500 nm with and without NOBL-1 (10−6 M. In addition, we noted rats’ responses to light with vardenafil (10−6 M, a phosphodiesterase-5 (PDE-5 inhibitor. Next, responses to light in the presence of a guanylate cyclase inhibitor, ODQ (1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (10−5 M, were measured. All measurements were performed in pretreated L-NAME (10−4 M conditions to inhibit endogenous NO production. Results: Corpus cavernosal smooth muscle, precontracted with noradrenaline, was unchanged by light irradiation in the absence of NOBL-1. However, in the presence of NOBL-1, corpus cavernosal smooth muscle, precontracted with noradrenaline, relaxed in response to light irradiation. After blue light irradiation ceased, tension returned. In addition, the light response was obviously enhanced in the presence of a PDE-5 inhibitor. Conclusions: This study showed that rat corpus cavernosal smooth muscle relaxation can be light-controlled using NOBL-1, a novel, light sensitive NO releaser. Though further in vivo studies are needed to investigate possible usefulness, NOBL-1 may be prove to be a useful tool for erectile dysfunction therapy, specifically in the field of penile rehabilitation.

  11. Phenylethylamine and tyramine are mixed-acting sympathomimetic amines in the brain.

    Science.gov (United States)

    Knoll, J; Miklya, I; Knoll, B; Markó, R; Rácz, D

    1996-01-01

    On the helical strip of a capacitance vessel, the pulmonary artery of the rabbit, phenylethylamine (PEA) and tyramine act solely via displacement of noradrenaline from their storage sites and this effect is inhibited by desmethylimipramine (DMI). In contrast, on a resistance vessel, the perfused central ear artery of the rabbit, PEA enhances stimulation induced contractions in 0.2-0.8 microgram/ml concentration [catecholaminergic activity enhancer (CAE) effect], and increases smooth muscle tone (noradrenaline displacing effect) in 4-6 micrograms/ml concentration. This latter effect only is blocked by DMI. Tyramine acts similarly and is more potent than PEA. On the isolated brain stem PEA, tyramine and (-)methamphetamine are, in the presence of cocaine and DMI, highly potent enhancers of stimulation induced release of 3H-noradrenaline, 3H-dopamine and 3H-serotonin. Compounds with specific CAE effect in the brain, (-)deprenyl and 1-phenyl-2-propylaminopentane [(-)PPAP], antagonize tetrabenazine-induced depression of performance of rats in the shuttle box. PEA and tyramine, which are rapidly metabolized in vivo, are ineffective in this test up to 40 mg/kg, whereas (-)methamphetamine, the stable PEA derivative, is highly effective. Compounds with CAE effect enhance at low concentrations the slow inward Ca2+ current in the sino-auricular fibers of the frog heart and inhibit it in high concentration. PEA and tyramine enhance Ca2+ influx from 0.05 to 4 micrograms/ml and inhibit it in 8 micrograms/ml. In conclusion, PEA and tyramine stimulate primarily coupling of action potential to transmitter release in the catecholaminergic neurons in the brain and displace catecholamines in higher concentration only.

  12. Developmental vitamin D deficiency alters multiple neurotransmitter systems in the neonatal rat brain.

    Science.gov (United States)

    Kesby, James P; Turner, Karly M; Alexander, Suzanne; Eyles, Darryl W; McGrath, John J; Burne, Thomas H J

    2017-11-01

    Epidemiological evidence suggests that developmental vitamin D (DVD) deficiency is a risk factor for neuropsychiatric disorders, such as schizophrenia. DVD deficiency in rats is associated with altered brain structure and adult behaviours indicating alterations in dopamine and glutamate signalling. Developmental alterations in dopamine neurotransmission have also been observed in DVD-deficient rats but a comprehensive assessment of brain neurochemistry has not been undertaken. Thus, the current study determined the regional concentrations of dopamine, noradrenaline, serotonin, glutamine, glutamate and γ-aminobutyric acid (GABA), and associated metabolites, in DVD-deficient neonates. Sprague-Dawley rats were fed a vitamin D deficient diet or control diet six weeks prior to mating until birth and housed under UVB-free lighting conditions. Neurotransmitter concentration was assessed by high-performance liquid chromatography on post-mortem neonatal brain tissue. Ubiquitous reductions in the levels of glutamine (12-24%) were observed in DVD-deficient neonates compared with control neonates. Similarly, in multiple brain regions DVD-deficient neonates had increased levels of noradrenaline and serine compared with control neonates. In contrast, increased levels of dopamine and decreased levels of serotonin in DVD-deficient neonates were limited to striatal subregions compared with controls. Our results confirm that DVD deficiency leads to changes in multiple neurotransmitter systems in the neonate brain. Importantly, this regionally-based assessment in DVD-deficient neonates identified both widespread neurotransmitter changes (glutamine/noradrenaline) and regionally selective neurotransmitter changes (dopamine/serotonin). Thus, vitamin D may have both general and local actions depending on the neurotransmitter system being investigated. Taken together, these data suggest that DVD deficiency alters neurotransmitter systems relevant to schizophrenia in the developing rat

  13. Pharmacological identification of β-adrenoceptor subtypes mediating isoprenaline-induced relaxation of guinea pig colonic longitudinal smooth muscle.

    Science.gov (United States)

    Chino, Daisuke; Sone, Tomoyo; Yamazaki, Kumi; Tsuruoka, Yuri; Yamagishi, Risa; Shiina, Shunsuke; Obara, Keisuke; Yamaki, Fumiko; Higai, Koji; Tanaka, Yoshio

    2018-01-01

    Object We aimed to identify the β-adrenoceptor (β-AR) subtypes involved in isoprenaline-induced relaxation of guinea pig colonic longitudinal smooth muscle using pharmacological and biochemical approaches. Methods Longitudinal smooth muscle was prepared from the male guinea pig ascending colon and contracted with histamine prior to comparing the relaxant responses to three catecholamines (isoprenaline, adrenaline, and noradrenaline). The inhibitory effects of subtype-selective β-AR antagonists on isoprenaline-induced relaxation were then investigated. Results The relaxant potencies of the catecholamines were ranked as: isoprenaline > noradrenaline ≈ adrenaline, whereas the rank order was isoprenaline > noradrenaline > adrenaline in the presence of propranolol (a non-selective β-AR antagonist; 3 × 10 -7 M). Atenolol (a selective β 1 -AR antagonist; 3 × 10 -7 -10 -6  M) acted as a competitive antagonist of isoprenaline-induced relaxation, and the pA 2 value was calculated to be 6.49 (95% confidence interval: 6.34-6.83). The relaxation to isoprenaline was not affected by ICI-118,551 (a selective β 2 -AR antagonist) at 10 -9 -10 -8  M, but was competitively antagonized by 10 -7 -3 × 10 -7  M, with a pA 2 value of 7.41 (95% confidence interval: 7.18-8.02). In the presence of propranolol (3 × 10 -7 M), the relaxant effect of isoprenaline was competitively antagonized by bupranolol (a non-selective β-AR antagonist), with a pA 2 value of 5.90 (95% confidence interval: 5.73-6.35). Conclusion These findings indicated that the β-AR subtypes involved in isoprenaline-induced relaxation of colonic longitudinal guinea pig muscles are β 1 -AR and β 3 -AR.

  14. Cardiac autonomic tone during trandolapril-irbesartan low-dose combined therapy in hypertension: a pilot project.

    Science.gov (United States)

    Franchi, F; Lazzeri, C; Foschi, M; Tosti-Guerra, C; Barletta, G

    2002-08-01

    Pharmacological and clinical studies on the effects of angiotensin-converting enzyme (ACE) inhibitors support the idea of a central role played Angiotensin II which is able to cause cardiovascular and renal diseases also independently of its blood pressure elevating effects. The present investigation was aimed at evaluating the effect(s) of three different pharmacological regimens on both blood pressure and sympathetic drive in uncomplicated essential hypertension, by means of blood pressure laboratory measurements and ambulatory monitoring, 24-h heart rate variability and plasma noradrenaline levels. Thus, an ACE-inhibitor monotherapy (trandolapril, 2 mg/day), an AT(1)-receptor antagonist monotherapy (irbesartan, 300 mg/day), their low-dose combination (0.5 mg/day plus 150 mg/day, respectively) and placebo were given, in a randomised, single-blind, crossover fashion for a period of 3 weeks each to 12 mild essential hypertensives. Power spectral analysis (short recordings) and noradrenaline measurements were also performed in the supine position and after a postural challenge (60 degrees head-up tilting test: HUT). The low-dose combination therapy induced the greatest reduction in LF component and in LF/HF ratio, both in the resting and tilted positions, as well as in blood pressure. However, the physiological autonomic response to HUT was maintained. Noradrenaline plasma levels were lower after the combined therapy than after each drug alone. Our data demonstrate that in mild and uncomplicated essential hypertension, the chronic low-dose combination therapy with an ACE-inhibitor and an AT(1)-antagonist is more effective than the recommended full-dose monotherapy with either drug in influencing the autonomic regulation of the heart, suggesting a relative reduction in sympathetic drive both at cardiac and systemic levels.

  15. The vasorelaxant effect of viscum album leaf extract is nediated by ...

    African Journals Online (AJOL)

    Viscum album leaf extract has a folk reputation as an antihypertensive agent in Nigeria. Evidence suggests that it has a relaxant effect on smooth muscle. The present study was designed to investigate the role of calcium in the vasorelaxant effect of this extract. Concentration response studies to noradrenaline, KCl and ...

  16. Sequential serotonin and noradrenalin associated processes involved in postpartum blues

    NARCIS (Netherlands)

    Doornbos, B.; Fekkes, D.; Tanke, M.A.; de Jonge, P.; Korf, J.

    2008-01-01

    Objective: We investigated whether postpartum blues was related to changes in parameters of noradrenergic and serotonergic functioning. Methods: From 26 healthy pregnant women blood was collected at the End of pregnancy and 5 days and 6 weeks postpartum. Serotonergic parameters were: platelet

  17. Sustained prejunctional facilitation of noradrenergic neurotransmission by adrenaline as a co-transmitter in the portal vein of freely moving rats

    NARCIS (Netherlands)

    COPPES, RP; Freie, I.; SMIT, J; ZAAGSMA, J

    1994-01-01

    1 The duration of the facilitatory effect of adrenaline on the electrically evoked overflow of noradrenaline was studied in the portal vein of permanently adreno-demedullated freely moving rats. 2 Rats were infused with adrenaline (20 or 100 ng min(-1)) for 2 h. After an interval of 1 h, when plasma

  18. Beta-blockers influence the short-term and long-term prognostic information of natriuretic peptides and catecholamines in chronic heart failure independent from specific agents.

    Science.gov (United States)

    Frankenstein, Lutz; Nelles, Manfred; Slavutsky, Maxim; Schellberg, Dieter; Doesch, Andreas; Katus, Hugo; Remppis, Andrew; Zugck, Christian

    2007-10-01

    In chronic heart failure (CHF), the physiologic effects of natriuretic peptides and catecholamines are interdependent. Furthermore, reports state an agent-dependent effect of individual beta-blockers on biomarkers. Data on the short-term and long-term predictive power comparing these biomarkers as well as accounting for the influence of beta-blocker treatment both on the marker or the resultant prognostic information are scarce. We included 513 consecutive patients with systolic CHF, measured atrial natriuretic peptide (ANP), N-terminal prohormone brain natriuretic peptide (NTproBNP), noradrenaline, and adrenaline, and monitored them for 90 +/- 25 months. Death or the combination of death and cardiac transplantation at 1 year, 5 years, and overall follow-up were considered end points. Compared with patients not taking beta-blockers, patients taking beta-blockers had significantly lower levels of catecholamines but not natriuretic peptides. Only for adrenaline was the amount of this effect related to the specific beta-blocker chosen. Receiver operating characteristic curves demonstrated superior prognostic accuracy for NTproBNP both at the 1- and 5-year follow-up compared with ANP, noradrenaline, and adrenaline. In multivariate analysis including established risk markers (New York Heart Association functional class, left ventricular ejection fraction, peak oxygen uptake, and 6-minute walk test), of all neurohumoral parameters, only NTproBNP remained an independent predictor for both end points. Long-term beta-blocker therapy is associated with decreased levels of plasma catecholamines but not natriuretic peptides. This effect is independent from the actual beta-blocker chosen for natriuretic peptides and noradrenaline. In multivariate analysis, both for short-term and long-term prediction of mortality or the combined end point of death and cardiac transplantation, only NTproBNP remained independent from established clinical risk markers.

  19. Pre- and post-synaptic sympathetic function in human hibernating myocardium

    International Nuclear Information System (INIS)

    John, Anna S.; Pepper, John R.; Dreyfus, Gilles D.; Pennell, Dudley J.; Mongillo, Marco; Khan, Muhammad T.; Depre, Christophe; Rimoldi, Ornella E.; Camici, Paolo G.

    2007-01-01

    Impaired pre-synaptic noradrenaline uptake-1 mechanism has been reported in a swine model of hibernating myocardium (HM). To ascertain whether adrenergic neuroeffector abnormalities are present in human HM, we combined functional measurements in vivo using cardiovascular magnetic resonance (CMR) and positron emission tomography (PET) to assess pre- and post-synaptic sympathetic function. Twelve patients with coronary artery disease and chronic left ventricular (LV) dysfunction underwent CMR at baseline and 6 months after bypass for assessment of regional and global LV function and identification of segments with reversible dysfunction. Before surgery, myocardial noradrenaline uptake-1 ([ 11 C]meta-hydroxy-ephedrine; HED) and β-adrenoceptor (β-AR) density ([ 11 C]CGP-12177) were measured with PET. Patient PET data were compared with those in 18 healthy controls. The volume of distribution (V d ) of HED in HM (47.95±28.05 ml/g) and infarcted myocardium (42.69±25.76 ml/g) was significantly reduced compared with controls (66.09±14.48 ml/g). The V d of HED in normal myocardium (49.93±20.48 ml/g) of patients was also lower than that in controls and the difference was close to statistical significance (p=0.06). Myocardial β-AR density was significantly lower in HM (5.49±2.35 pmol/g), infarcted (4.82±2.61 pmol/g) and normal (5.86±1.81 pmol/g) segments of patients compared with healthy controls (8.61±1.32 pmol/g). Noradrenaline uptake-1 mechanism and β-AR density are reduced in the myocardium of patients with chronic LV dysfunction and evidence of HM. The increased sympathetic activity to the heart in these patients is a generalised rather than regional phenomenon which is likely to contribute to the remodelling process of the whole LV rather than playing a causative role in HM. (orig.)

  20. Pre- and post-synaptic sympathetic function in human hibernating myocardium

    Energy Technology Data Exchange (ETDEWEB)

    John, Anna S.; Pepper, John R.; Dreyfus, Gilles D.; Pennell, Dudley J. [Imperial College, Hammersmith Hospital, National Heart and Lung Institute, London (United Kingdom); Mongillo, Marco; Khan, Muhammad T. [Imperial College, Hammersmith Hospital, Medical Research Council Clinical Sciences Centre, London (United Kingdom); Depre, Christophe [University of Medicine and Dentistry New Jersey, Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, New Jersey, NJ (United States); University of Medicine and Dentistry New Jersey, Cardiovascular Research Institute, Department of Medicine, New Jersey, NJ (United States); Rimoldi, Ornella E. [Imperial College, Hammersmith Hospital, National Heart and Lung Institute, London (United Kingdom); Imperial College, Hammersmith Hospital, Medical Research Council Clinical Sciences Centre, London (United Kingdom); New York Medical College, Cardiovascular Research Institute, Department of Medicine, Valhalla, NY (United States); Camici, Paolo G. [Imperial College, Hammersmith Hospital, National Heart and Lung Institute, London (United Kingdom); Imperial College, Hammersmith Hospital, Medical Research Council Clinical Sciences Centre, London (United Kingdom)

    2007-12-15

    Impaired pre-synaptic noradrenaline uptake-1 mechanism has been reported in a swine model of hibernating myocardium (HM). To ascertain whether adrenergic neuroeffector abnormalities are present in human HM, we combined functional measurements in vivo using cardiovascular magnetic resonance (CMR) and positron emission tomography (PET) to assess pre- and post-synaptic sympathetic function. Twelve patients with coronary artery disease and chronic left ventricular (LV) dysfunction underwent CMR at baseline and 6 months after bypass for assessment of regional and global LV function and identification of segments with reversible dysfunction. Before surgery, myocardial noradrenaline uptake-1 ([{sup 11}C]meta-hydroxy-ephedrine; HED) and {beta}-adrenoceptor ({beta}-AR) density ([{sup 11}C]CGP-12177) were measured with PET. Patient PET data were compared with those in 18 healthy controls. The volume of distribution (V{sub d}) of HED in HM (47.95{+-}28.05 ml/g) and infarcted myocardium (42.69{+-}25.76 ml/g) was significantly reduced compared with controls (66.09{+-}14.48 ml/g). The V{sub d} of HED in normal myocardium (49.93{+-}20.48 ml/g) of patients was also lower than that in controls and the difference was close to statistical significance (p=0.06). Myocardial {beta}-AR density was significantly lower in HM (5.49{+-}2.35 pmol/g), infarcted (4.82{+-}2.61 pmol/g) and normal (5.86{+-}1.81 pmol/g) segments of patients compared with healthy controls (8.61{+-}1.32 pmol/g). Noradrenaline uptake-1 mechanism and {beta}-AR density are reduced in the myocardium of patients with chronic LV dysfunction and evidence of HM. The increased sympathetic activity to the heart in these patients is a generalised rather than regional phenomenon which is likely to contribute to the remodelling process of the whole LV rather than playing a causative role in HM. (orig.)

  1. A mouse model of non-motor symptoms in Parkinson’s disease: focus on pharmacological interventions targeting affective dysfunctions

    Directory of Open Access Journals (Sweden)

    Alessandra eBonito Oliva

    2014-08-01

    Full Text Available Non-motor symptoms, including psychiatric disorders, are increasingly recognized as a major challenge in the treatment of Parkinson’s disease (PD. These ailments, which often appear in the early stage of the disease, affect a large number of patients and are only partly resolved by conventional antiparkinsonian medications, such as L-DOPA. Here, we investigated non-motor symptoms of PD in a mouse model based on bilateral injection of the toxin 6-hydroxydopamine (6-OHDA in the dorsal striatum. This model presented only subtle gait modifications, which did not affect horizontal motor activity in the open-field test. Bilateral 6-OHDA lesion also impaired olfactory discrimination, in line with the anosmia typically observed in early stage parkinsonism. The effect of 6-OHDA was then examined for mood-related dysfunctions. Lesioned mice showed increased immobility in the forced swim test and tail suspension test, two behavioral paradigms of depression. Moreover, the lesion exerted anxiogenic effects, as shown by reduced time spent in the open arms, in the elevated plus maze test, and by increased thigmotaxis in the open-field test. L-DOPA did not modify depressive- and anxiety-like behaviors, which were instead counteracted by the dopamine D2/D3 receptor agonist, pramipexole. Reboxetine, a noradrenaline reuptake inhibitor, was also able to prevent the depressive and anxiogenic effects produced by the lesion with 6-OHDA. Interestingly, pre-treatment with desipramine prior to injection of 6-OHDA, which is commonly used to preserve noradrenaline neurons, did not modify the effect of the lesion on depressive- and anxiety-like behaviors. Thus, in the present model, mood-related conditions are independent of the reduction of noradrenaline caused by 6-OHDA. Based on these findings we propose that the anti-depressive and anxiolytic action of reboxetine is mediated by promoting dopamine transmission through blockade of dopamine uptake from residual

  2. Modified cytoplasmic Ca2+ sequestration contributes to spinal cord injury-induced augmentation of nerve-evoked contractions in the rat tail artery.

    Directory of Open Access Journals (Sweden)

    Hussain Al Dera

    Full Text Available In rat tail artery (RTA, spinal cord injury (SCI increases nerve-evoked contractions and the contribution of L-type Ca2+ channels to these responses. In RTAs from unoperated rats, these channels play a minor role in contractions and Bay K8644 (L-type channel agonist mimics the effects of SCI. Here we investigated the mechanisms underlying the facilitatory actions of SCI and Bay K8644 on nerve-evoked contractions of RTAs and the hypothesis that Ca2+ entering via L-type Ca2+ channels is rapidly sequestered by the sarcoplasmic reticulum (SR limiting its role in contraction. In situ electrochemical detection of noradrenaline was used to assess if Bay K8644 increased noradrenaline release. Perforated patch recordings were used to assess if SCI changed the Ca2+ current recorded in RTA myocytes. Wire myography was used to assess if SCI modified the effects of Bay K8644 and of interrupting SR Ca2+ uptake on nerve-evoked contractions. Bay K8644 did not change noradrenaline-induced oxidation currents. Neither the size nor gating of Ca2+ currents differed between myocytes from sham-operated (control and SCI rats. Bay K8644 increased nerve-evoked contractions in RTAs from both control and SCI rats, but the magnitude of this effect was reduced by SCI. By contrast, depleting SR Ca2+ stores with ryanodine or cyclopiazonic acid selectively increased nerve-evoked contractions in control RTAs. Cyclopiazonic acid also selectively increased the blockade of these responses by nifedipine (L-type channel blocker in control RTAs, whereas ryanodine increased the blockade produced by nifedipine in both groups of RTAs. These findings suggest that Ca2+ entering via L-type channels is normally rapidly sequestered limiting its access to the contractile mechanism. Furthermore, the findings suggest SCI reduces the role of this mechanism.

  3. Secretion of [Met]enkephalyl-Arg6-Phe7-related peptides and catecholamines from bovine adrenal chromaffin cells: modification by changes in cyclic AMP and by treatment with reserpine.

    Science.gov (United States)

    Adams, M; Boarder, M R

    1987-07-01

    Investigations into the effects of culturing bovine adrenal chromaffin cells in the presence (72 h) of dibutyryl cyclic AMP, forskolin, and reserpine on the level and release of [Met]enkephalyl-Arg6-Phe7 immunoreactivity, noradrenaline, and adrenaline are reported. The assay for [Met]enkephalyl-Arg6-Phe7 immunoreactivity recognises both peptide B, the 31-amino acid carboxy-terminal segment of proenkephalin, and its heptapeptide fragment, [Met]enkephalyl-Arg6-Phe7. Treatments that elevate cyclic AMP increase the amount of peptide immunoreactivity in these cells; this is predominantly peptide B-like immunoreactivity in both control cells and cyclic AMP-elevated cells. Treatment with reserpine gives no change in total immunoreactivity levels, but does not result in increased accumulation of the heptapeptide [Met]enkephalyl-Arg6-Phe7 at the expense of immunoreactivity that elutes with its immediate precursor, peptide B. Cyclic AMP treatment causes either no change or a decrease in levels of accumulated noradrenaline and adrenaline. However, the release of [Met]enkephalin-Arg6-Phe7 immunoreactivity, noradrenaline, and adrenaline is increased by 72-h pretreatment with forskolin or dibutyryl cyclic AMP, whether release is stimulated by nicotine or elevated potassium. In each case the molecular form of [Met]enkephalyl-Arg6-Phe7 immunoreactivity that is released approximately reflects the cell content. Pretreatment with reserpine has no effect on the total [Met]enkephalyl-Arg6-Phe7 immunoreactivity released, but does result in an increased release of the heptapeptide and a decrease in release of peptide B-like immunoreactivity. The studies suggest that the levels of [Met]enkephalyl-Arg6-Phe7 and peptide B available for release are controlled both at the level of proenkephalin synthesis and at the level of double-basic residue proteolysis.

  4. Electrocoagulation of the Locus coeruleus and the plasma catecholamine responses to immobilization stress in normotensive and hypertensive rats

    International Nuclear Information System (INIS)

    Dronjak, S.; Nikolic, J.; Varagic, V.M.

    1998-01-01

    The Locus coeruleus (LC), the largest noradrenergic nucleus in the brain, plays a major role in behavioral arousal in response to novel or stressful stimuli (Foote et al, 1983). An interesting feature of the LC is the degree of plasticity it displays in response to stress or drug treatment. For example, electrophysiological evidence suggests that sprouting of LC axons may occur following repeated stress (Sakaguchi and Nakamura, 1990). Stress increases LC firing rate and results in increased levels of noradrenaline (Glavin et al, 1983). High concentrations of noradrenergic neurons in LC indicated that this structure might have an integrative role in the blood pressure regulation. Spontaneously hypertensive rats (SHP) are widely used as a model of human essential hypertension. These animals exhibit enhanced sympathetic activity (Brody et al, 1980). It was therefore of interest to study the role of LC in normotensive and spontaneously hypertensive rats, and the effect of unilateral and bilateral electrocoagulation of the LC on the plasma concentration of noradrenaline and adrenaline during immobilization stress. (author)

  5. Effect of Ramadan Fasting on Stress Neurohormones in Women with Polycystic Ovary Syndrome.

    Science.gov (United States)

    Zangeneh, Farideh; Salman Yazdi, Reza; Naghizadeh, Mohammad Mehdi; Abedinia, Nasrin

    2015-06-01

    To determine the effects of Ramadan fasting on serum levels of stress neurohormones in Iranian women with polycystic ovary syndrome (PCOS). This study was a clinical trial and was performed during July 2011 (month of Ramadan) in Royan institute, Tehran. A total of 40 women who were aged 20-40 years and known cases of PCOS and had no other medical diseases were included in the study. They were divided into two groups as follows: (i) study group (n = 20) who participated in Ramadan fasting and (ii) control group (n = 20) who did not participate in fasting. For evaluating Ramadan's effect on the level of neurohormones serum level of the following variables were evaluated before and after Ramadan: cortisol, adrenaline (A), noradrenalin (NA), beta-endorphin (β-End), insulin, as well as sex hormones including follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. In the study group after Ramadan serum cortisol and nor-adrenaline levels were significantly lower than the initial levels obtained at beginning of Ramadan (p Ramadan fasting decreases stress neurohormones in women with PCOS.

  6. Hypothalamic digoxin, hemispheric chemical dominance, and creativity.

    Science.gov (United States)

    Kurup, Ravi Kumar; Kurup, Parameswara Achutha

    2003-04-01

    The human hypothalamus produces an endogenous membrane Na(+)-K+ ATPase inhibitor, digoxin, which regulates neuronal transmission. The digoxin status and neurotransmitter patterns were studied in creative and non-creative individuals, as well as in individuals with differing hemispheric dominance, in order to find out the role of cerebral dominance in this respect. The activity of HMG CoA reductase and serum levels of digoxin, magnesium, tryptophan catabolites, and tyrosine catabolites were measured in creative/non-creative individuals, and in individuals with differing hemispheric dominance. In creative individuals there was increased digoxin synthesis, decreased membrane Na(+)-K+ ATPase activity, increased tryptophan catabolites (serotonin, quinolinic acid, and nicotine), and decreased tyrosine catabolites (dopamine, noradrenaline, and morphine). The pattern in creative individuals correlated with right hemispheric dominance. In non-creative individuals there was decreased digoxin synthesis, increased membrane Na(+)-K+ ATPase activity, decreased tryptophan catabolites (serotonin, quinolinic acid, and nicotine), and increased tyrosine catabolites (dopamine, noradrenaline, and morphine). This pattern in non-creative individuals correlated with that obtained in left hemispheric chemical dominance. Hemispheric chemical dominance and hypothalamic digoxin could regulate the predisposition to creative tendency.

  7. Hypothalamic digoxin, hemispheric chemical dominance, and sleep.

    Science.gov (United States)

    Kurup, Ravi Kumar; Kurup, Parameswara Achutha

    2003-04-01

    The isoprenoid path way produces endogenous digoxin, a substance that can regulate neurotransmitter and amino acid transport. Digoxin synthesis and neurotransmitter patterns were assessed in individuals with chronic insomnia. The patterns were compared in those with right hemispheric and left hemispheric dominance. The activity of HMG GoA reductase and serum levels of digoxin, magnesium, tryptophan catabolites, and tyrosine catabolites were measured in individuals with chronic insomnia and in individuals with differing hemispheric dominance. Digoxin synthesis was increased with upregulated tryptophan catabolism (increased levels of serotonin, strychnine, and nicotine), and downregulated tyrosine catabolism (decreased levels of dopamine, noradrenaline, and morphine) in those with chronic insomnia and right hemispheric chemical dominance. Digoxin synthesis was reduced with downregulated tryptophan catabolism (decreased levels of serotonin, strychnine, and nicotine) and upregulated tyrosine catabolism (increased levels of dopamine, noradrenaline, and morphine) in those with normal sleep patterns and left hemispheric chemical dominance. Hypothalamic digoxin plays a central role in the regulation of sleep behavior. Hemispheric chemical dominance in relation to digoxin status is also crucial.

  8. Catecholaminergic and cholinergic systems of mouse brain are modulated by LMN diet, rich in theobromine, polyphenols and polyunsaturated fatty acids.

    Science.gov (United States)

    Fernández-Fernández, Laura; Esteban, Gerard; Giralt, Mercedes; Valente, Tony; Bolea, Irene; Solé, Montse; Sun, Ping; Benítez, Susana; Morelló, José Ramón; Reguant, Jordi; Ramírez, Bartolomé; Hidalgo, Juan; Unzeta, Mercedes

    2015-04-01

    The possible modulatory effect of the functional LMN diet, rich in theobromine, polyphenols and polyunsaturated fatty acids, on the catecholaminergic and cholinergic neurotransmission, affecting cognition decline during aging has been studied. 129S1/SvlmJ mice were fed for 10, 20, 30 and 40 days with either LMN or control diets. The enzymes involved in catecholaminergic and cholinergic metabolism were determined by both immunohistological and western blot analyses. Noradrenalin, dopamine and other metabolites were quantified by HPLC analysis. Theobromine, present in cocoa, the main LMN diet component, was analysed in parallel using SH-SY5Y and PC12 cell lines. An enhanced modulatory effect on both cholinergic and catecholaminergic transmissions was observed on 20 day fed mice. Similar effect was observed with theobromine, besides its antioxidant capacity inducing SOD-1 and GPx expression. The enhancing effect of the LMN diet and theobromine on the levels of acetylcholine-related enzymes, dopamine and specially noradrenalin confirms the beneficial role of this diet on the "cognitive reserve" and hence a possible reducing effect on cognitive decline underlying aging and Alzheimer's disease.

  9. Comparison of the effects of the K(+)-channel openers cromakalim and minoxidil sulphate on vascular smooth muscle.

    Science.gov (United States)

    Wickenden, A. D.; Grimwood, S.; Grant, T. L.; Todd, M. H.

    1991-01-01

    1 The actions of the potassium channel openers, cromakalim and minoxidil sulphate, were compared in a range of isolated blood vessel preparations. 2 Cromakalim and minoxidil sulphate inhibited spontaneous mechanical activity of the guinea-pig portal vein and relaxed the noradrenaline precontracted rat aorta with similar potency. In contrast, minoxidil sulphate was less potent than cromakalim in inhibiting spontaneous activity in the rat portal vein and was essentially inactive in the noradrenaline precontracted rat mesenteric artery and rabbit aorta. 3 Minoxidil sulphate did not antagonize the effects of cromakalim in the rabbit aorta indicating it was not acting as a partial 'agonist'. 4 Charybdotoxin, noxiustoxin and rubidium failed to discriminate between cromakalim and minoxidil sulphate indicating that the apparently selective effects of minoxidil sulphate were not mediated by either Ca(2+)-activated potassium channels, delayed rectifiers or rubidium impermeable potassium channels. 5 Glibenclamide antagonized the effects of cromakalim in an apparently competitive manner whereas the effects of minoxidil sulphate were antagonized in a non-competitive manner. The involvement of subtypes of ATP-sensitive potassium channels is discussed. PMID:1878752

  10. SENSITIVE EFFECTS OF POTASSIUM AND CALCIUM CHANNEL BLOCKING AND ATP-SENSITIVE POTASSIUM CHANNEL ACTIVATORS ON SEMINAL VESICLE SMOOTH MUSCLE CONTRACTIONS

    Directory of Open Access Journals (Sweden)

    H SADRAEI

    2000-12-01

    Full Text Available Background. Seminal vesicle smooth muscle contraction is mediated through sympathetic and parasympathetic neurons activity. Although seminal vesicle plays an important role in male fertility, but little attention is given to mechanism involved in contraction of this organ.
    Methods. In this study effects of drugs which activate ATP - sensitive K channels and blockers of K and Ca channels were examined on contraction of guinea - pig isolated seminal vesicle due to electrical filled stimulation (EFS, noradrenaline, carbachol and KCI.
    Results. The K channel blocker tetraethyl ammonium potentate the EFS responses at all frequencies, while, the ATP - sensitive K channel inhibitor glibenclamide and the K channel opener levcromakalim, diazoxide, minoxidil and Ca channel blocker nifedipine all had relaxant effect on guinea - pig seminal vesicle.
    Discussion. This study indicate that activities of K and Ca channels is important in regulation of seminal vesicle contraction due to nerve stimulation, noradrenaline or carbachol.

  11. Kidney, lower limb and whole-body uptake and release of catecholamines in alcoholic liver disease

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Ring-Larsen, H; Christensen, N J

    1988-01-01

    Regional (kidney, lower limb) and whole-body kinetics of endogenous noradrenaline (NA) and tritium-labelled L-noradrenaline (3H-NA) were determined in patients with alcoholic liver disease (one alcoholic hepatitis, 12 cirrhosis) and in control subjects (n = 6) in order to get information...... (0.69 vs. 0.45 pmol/min.g per pmol/min.g in controls, P less than 0.005) but not in the lower limb (0.23 vs. 0.49 in controls, P less than 0.01). In patients with ascites the spillover rate of NA from the kidney into plasma (1.9 pmol/min.g) was significantly increased (P less than 0.02) compared...... to controls and non-ascitic patients (1.2 and 1.0 pmol/min.g, respectively. Patients and control kidneys and limbs extracted almost the same fraction of 3H-NA (0.34 vs. 0.32 NS and 0.34 vs. 0.37 NS, respectively). Whole-body clearance of 3H-NA was not significantly different in cirrhotics and controls (median...

  12. The neurobiology of social play and its rewarding value in rats

    Science.gov (United States)

    Vanderschuren, Louk J.M.J.; Achterberg, E.J. Marijke; Trezza, Viviana

    2016-01-01

    In the young of many mammalian species, including humans, a vigorous and highly rewarding social activity is abundantly expressed, known as social play behaviour. Social play is thought to be important for the development of social, cognitive and emotional processes and their neural underpinnings, and it is disrupted in pediatric psychiatric disorders. Here, we summarize recent progress in our understanding of the brain mechanisms of social play behaviour, with a focus on its rewarding properties. Opioid, endocannabinoid, dopamine and noradrenaline systems play a prominent role in the modulation of social play. Of these, dopamine is particularly important for the motivational properties of social play. The nucleus accumbens has been identified as a key site for opioid and dopamine modulation of social play. Endocannabinoid influences on social play rely on the basolateral amygdala, whereas noradrenaline modulates social play through the basolateral amygdala, habenula and prefrontal cortex. In sum, social play behaviour is the result of coordinated activity in a network of corticolimbic structures, and its monoamine, opioid and endocannabinoid innervation. PMID:27587003

  13. Hypothalamic digoxin, hemispheric chemical dominance, and spirituality.

    Science.gov (United States)

    Kurup, Ravi Kumar; Kurup, Parameswara Achutha

    2003-03-01

    The isoprenoid pathway was assessed in atheistic and spiritually inclined individuals. The pathway was also assessed in individuals with differing hemispheric dominance to assess whether hemispheric dominance has a correlation with spiritual and atheistic tendency. HMG CoA reductase activity, serum digoxin, RBC membrane Na(+)-K+ ATPase activity, serum magnesium, and tyrosine/tryptophan catabolic patterns were assessed in spiritual/atheistic individuals and in those differing hemispheric dominance. In spiritually-inclined individuals, there was increased digoxin synthesis, decreased membrane Na(+)-K+ ATPase activity, increased tryptophan catabolites (serotonin, quinolinic acid, and nicotine), and decreased tyrosine catabolites (dopamine, noradrenaline, and morphine). The pattern in spiritually-inclined individuals correlated with right hemispheric chemical dominance. In atheistic individuals there was decreased digoxin synthesis, increased membrane Na(+)-K+ ATPase activity, decreased tryptophan catabolities (serotonin, quinolinic acid, and nicotine), and increased tyrosine catabolites (dopamine, noradrenaline, and morphine). This pattern in atheistic individuals correlated with that obtained in left hemispheric chemical dominance. Hemispheric chemical dominance and hypothalamic digoxin could regulate the predisposition to spirituality or atheism.

  14. Detection of neurotransmitters by a light scattering technique based on seed-mediated growth of gold nanoparticles

    International Nuclear Information System (INIS)

    Shang Li; Dong Shaojun

    2008-01-01

    A simple light scattering detection method for neurotransmitters has been developed, based on the growth of gold nanoparticles. Neurotransmitters (dopamine, L-dopa, noradrenaline and adrenaline) can effectively function as active reducing agents for generating gold nanoparticles, which result in enhanced light scattering signals. The strong light scattering of gold nanoparticles then allows the quantitative detection of the neurotransmitters simply by using a common spectrofluorometer. In particular, Au-nanoparticle seeds were added to facilitate the growth of nanoparticles, which was found to enhance the sensing performance greatly. Using this light scattering technique based on the seed-mediated growth of gold nanoparticles, detection limits of 4.4 x 10 -7 M, 3.5 x 10 -7 M, 4.1 x 10 -7 M, and 7.7 x 10 -7 M were achieved for dopamine, L-dopa, noradrenaline and adrenaline, respectively. The present strategy can be extended to detect other biologically important molecules in a very fast, simple and sensitive way, and may have potential applications in a wide range of fields

  15. Detection of neurotransmitters by a light scattering technique based on seed-mediated growth of gold nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Shang Li; Dong Shaojun [State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Changchun 130022 (China)], E-mail: dongsj@ciac.jl.cn

    2008-03-05

    A simple light scattering detection method for neurotransmitters has been developed, based on the growth of gold nanoparticles. Neurotransmitters (dopamine, L-dopa, noradrenaline and adrenaline) can effectively function as active reducing agents for generating gold nanoparticles, which result in enhanced light scattering signals. The strong light scattering of gold nanoparticles then allows the quantitative detection of the neurotransmitters simply by using a common spectrofluorometer. In particular, Au-nanoparticle seeds were added to facilitate the growth of nanoparticles, which was found to enhance the sensing performance greatly. Using this light scattering technique based on the seed-mediated growth of gold nanoparticles, detection limits of 4.4 x 10{sup -7} M, 3.5 x 10{sup -7} M, 4.1 x 10{sup -7} M, and 7.7 x 10{sup -7} M were achieved for dopamine, L-dopa, noradrenaline and adrenaline, respectively. The present strategy can be extended to detect other biologically important molecules in a very fast, simple and sensitive way, and may have potential applications in a wide range of fields.

  16. Determination of free and conjugated catecholamines and L-3,4-dihydroxyphenylalanine in plasma and urine: evidence for a catechol-O-methyltransferase inhibitor in uraemia

    International Nuclear Information System (INIS)

    Demassieux, S.; Corneille, L.; Lachance, S.; Carriere, S.

    1981-01-01

    A sensitive, accurate and reproducible method has been developed for the determination of free and conjugated catecholamines and L-3,4-dihydroxyphenylalanine in plasma and urine. The assay involves the enzymatic conversion of these compounds to their radio-labelled O-methylated derivatives using catechol-O-methyltransferase and S-adenosyl-L-[methyl- 3 H]methionine. Recoveries of 75 +- 5% for dopamine, 70 +- 5% for adrenaline and 65 +- 5% for noradrenaline were obtained. The sensitivities were 0.5 pg for adrenaline and noradrenaline and 5-7 pg for dopamine and dihydroxyphenylalanine. Measurements of conjugated catecholamines were performed after mild acid hydrolysis for 20 min at 95 0 C. During this procedure no degradation of the catecholamines was observed. This assay led to the discovery of a dialyzable factor in the plasma of chronic uraemic patients which inhibits catechol-O-methyltransferase activity in vitro. The mean 22% inhibition observed for unhydrolyzed plasma increased to 42% after hydrolysis. The identity of this inhibitor which exists as an inactive conjugated form, probably a sulphate ester, and its implication in physiopathological disorders remain to be established. (Auth.)

  17. From symptoms to social functioning: differential effects of antidepressant therapy.

    Science.gov (United States)

    Kasper, S

    1999-05-01

    Significant impairments in social functioning frequently occur simultaneously with depressive symptoms. The implications of such impairments extend beyond the depressed individual to their family, friends and society at large. Classical rating scales such as the Hamilton rating scale for depression primarily assess the core symptoms of depression. A range of rating scales are available, both self-reporting and administered by clinician; however, many have been criticised for their unspecified conceptual background and for being complex and time-consuming. While antidepressants in general appear to improve social functioning, no clear advantage for any single class of agent has been reported. Recently, a new self-report rating scale, the Social Adaptation Self-evaluation Scale, has been developed and used to compare the novel selective noradrenaline reuptake inhibitor, reboxetine, with the selective serotonin re-uptake inhibitor, fluoxetine. The noradrenergic agent, reboxetine, was shown to be significantly more effective in improving social functioning than the serotonergic agent, fluoxetine. These findings are consistent with previous observations that noradrenaline may preferentially improve vigilance, motivation and self-perception.

  18. Correlation interrelation between level of catecholamines and indices of cholinesterase system at minor radiation dose influence on liquidators of the Chernobyl NPP

    International Nuclear Information System (INIS)

    Makashev, Zh.K.; Zhurnist, A.G.; Uteshev, A.G.; Abylaev, Zh.A.

    2004-01-01

    For assessment of functional condition of sympathoadrenal system adrenalin (A) and noradrenaline (NA) concentrations were investigated as well as NA/A ratio in day's urine of Chernobyl NPP liquidators. Concurrently, it was determined the contents of acetylcholine and activity of cholinesterase in the blood serum of persons exposed to minor radiation dose with calculation of correlation Pearson coefficient. (author)

  19. Insulin facilitates transport of macromolecules and nutrients to muscles

    DEFF Research Database (Denmark)

    Christensen, N J; Hilsted, J

    1993-01-01

    We previously showed that intravenous insulin increased plasma noradrenaline during euglycemia and without concomitant changes in plasma adrenaline. Insulin decreased plasma volume and increased the fractional escape rate of albumin from plasma. In normal subjects, oral glucose increased heart ra...... the blood to the extracellular space after food intake. This process may be greatly disturbed in insulin-dependent diabetic patients....

  20. Whole body and regional clearances of noradrenaline and adrenaline in man

    DEFF Research Database (Denmark)

    Christensen, N J; Galbo, H; Gjerris, A

    1984-01-01

    the clearance values based on arterial and venous sampling averaged 1.4 and 2.5 l/min, respectively (p less than 0.02). The difference in clearance values was due to peripheral uptake of NA averaging 45%. The plasma appearance rate on NA averaged 2.4 nmol/min before surgery and it increased to 9.5 nmol...... we found no correlation between clearance values based on venous and arterial sampling. In other experiments we measured the influence of physical exercise in young healthy subjects on the clearance rate of plasma adrenaline (A). The clearance of A, which at rest averaged 1.9 l/min tended to increase...

  1. Whole body and regional clearances of noradrenaline and adrenaline in man

    DEFF Research Database (Denmark)

    Christensen, N J; Galbo, H; Gjerris, Anne Cathrine Roslev

    1984-01-01

    we found no correlation between clearance values based on venous and arterial sampling. In other experiments we measured the influence of physical exercise in young healthy subjects on the clearance rate of plasma adrenaline (A). The clearance of A, which at rest averaged 1.9 l/min tended to increase...

  2. Catecholamine-induced vasoconstriction is sensitive to carbonic anhydrase I activation

    Directory of Open Access Journals (Sweden)

    Puscas I.

    2001-01-01

    Full Text Available We studied the relationship between alpha- and beta-adrenergic agonists and the activity of carbonic anhydrase I and II in erythrocyte, clinical and vessel studies. Kinetic studies were performed. Adrenergic agonists increased erythrocyte carbonic anhydrase as follows: adrenaline by 75%, noradrenaline by 68%, isoprenaline by 55%, and orciprenaline by 62%. The kinetic data indicated a non-competitive mechanism of action. In clinical studies carbonic anhydrase I from erythrocytes increased by 87% after noradrenaline administration, by 71% after orciprenaline and by 82% after isoprenaline. The increase in carbonic anhydrase I paralleled the increase in blood pressure. Similar results were obtained in vessel studies on piglet vascular smooth muscle. We believe that adrenergic agonists may have a dual mechanism of action: the first one consists of a catecholamine action on its receptor with the formation of a stimulus-receptor complex. The second mechanism proposed completes the first one. By this second component of the mechanism, the same stimulus directly acts on the carbonic anhydrase I isozyme (that might be functionally coupled with adrenergic receptors, so that its activation ensures an adequate pH for stimulus-receptor coupling for signal transduction into the cell, resulting in vasoconstriction.

  3. Effect of Ramadan Fasting on Stress Neurohormones in Women with Polycystic Ovary Syndrome.

    Directory of Open Access Journals (Sweden)

    Farideh Zangeneh

    2015-06-01

    Full Text Available To determine the effects of Ramadan fasting on serum levels of stress neurohormones in Iranian women with polycystic ovary syndrome (PCOS.This study was a clinical trial and was performed during July 2011 (month of Ramadan in Royan institute, Tehran. A total of 40 women who were aged 20-40 years and known cases of PCOS and had no other medical diseases were included in the study. They were divided into two groups as follows: (i study group (n = 20 who participated in Ramadan fasting and (ii control group (n = 20 who did not participate in fasting. For evaluating Ramadan's effect on the level of neurohormones serum level of the following variables were evaluated before and after Ramadan: cortisol, adrenaline (A, noradrenalin (NA, beta-endorphin (β-End, insulin, as well as sex hormones including follicle-stimulating hormone (FSH, luteinizing hormone (LH, and testosterone.In the study group after Ramadan serum cortisol and nor-adrenaline levels were significantly lower than the initial levels obtained at beginning of Ramadan (p < 0.05 as compared to control group.This study indicates that Ramadan fasting decreases stress neurohormones in women with PCOS.

  4. Early attempts to visualize cortical monoamine nerve terminals.

    Science.gov (United States)

    Hökfelt, Tomas

    2016-08-15

    The Falck-Hillarp, formaldehyde fluorescence method for the demonstration of monoamine neurons in a microscope was established in Lund, Sweden and published in 1962. In the same year Hillarp moved to Karolinska Institutet in Stockholm. Two years later Dahlström and Fuxe published the famous supplement in Acta Physiologica Scandinavica, describing the distribution of the dopamine, noradrenaline and serotonin cell groups in the rat brain. This landmark paper also represented an important contribution to an emerging discipline in neuroscience - chemical neuroanatomy. During the following years several modifications of the original method were developed, attempting to solve some shortcomings, one being the reproducible demonstration of noradrenaline nerve terminals in cortical regions. One result was the paper focused on in the present article, which also describes other efforts in the same direction going on in parallel, primarily, in Lund and Stockholm. As a result there was, in the mid 1970s, a fairly complete knowledge of the catecholamine systems in the rat brain. This article is part of a Special Issue entitled SI:50th Anniversary Issue. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Vascular effects of the Mangifera indica L. extract (Vimang).

    Science.gov (United States)

    Beltrán, Amada E; Alvarez, Yolanda; Xavier, Fabiano E; Hernanz, Raquel; Rodriguez, Janet; Núñez, Alberto J; Alonso, María J; Salaices, Mercedes

    2004-09-24

    The effects of the Mangiferia indica L. (Vimang) extract, and mangiferin (a C-glucosylxanthone of Vimang) on the inducible isoforms of cyclooxygenase (cyclooxygenase-2) and nitric oxide synthase (iNOS) expression and on vasoconstrictor responses were investigated in vascular smooth muscle cells and mesenteric resistance arteries, respectively, from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Vimang (0.5-0.1 mg/ml) and mangiferin (0.025 mg/ml) inhibited the interleukin-1beta (1 ng/ml)-induced iNOS expression more in SHR than in WKY, and cyclooxygenase-2 expression more in WKY than in SHR. Vimang (0.25-1 mg/ml) reduced noradrenaline (0.1-30 microM)- and U46619 (1 nM-30 microM)- but not KCl (15-70 mM)-induced contractions. Mangiferin (0.05 mg/ml) did not affect noradrenaline-induced contraction. In conclusion, the antiinflammatory action of Vimang would be related with the inhibition of iNOS and cyclooxygenase-2 expression, but not with its effect on vasoconstrictor responses. Alterations in the regulation of both enzymes in hypertension would explain the differences observed in the Vimang effect.

  6. Why is vitamin B6 effective in alleviating the symptoms of autism?

    Science.gov (United States)

    Sato, Kohji

    2018-06-01

    Many factors are reported to be involved in the complex pathophysiological processes of autism, suggesting that there is considerable variability in the manifestations of this disease. Several interventions are used to treat this disorder. Among them, vitamin B6 is widely used to treat the symptoms observed in autism. Vitamin B6 is beneficial for about half of autistic individuals in decreasing behavioral problems. However, until now, it remains unknown why vitamin B6 is effective for this disease. Although the exact pathogenesis is not defined, it is evident that certain neurotransmitter systems are impaired in the brains of autistic patients, causing the symptoms observed in the disease. In fact, impairment of many neurotransmitter systems has been reported, including GABA, serotonin, dopamine, and noradrenalin. Furthermore, vitamin B6 is important for the synthesis of many neurotransmitters, including GABA, serotonin, dopamine, noradrenalin, histamine, glycine, and d-serine, indicating that vitamin B6 supplementation may enhance many neurotransmitter systems. Thus, vitamin B6 supplementation can treat the impaired neurotransmitter systems in a given patient, even if the actual impaired neurotransmitter systems are not defined in that patient. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Mechanism of the cardiovascular activity of dibenzoxazepine in cats.

    Science.gov (United States)

    Lundy, P M

    1978-04-01

    Small i.v. doses of dibenzoxazepine (DBO) (50--400 microgram/kg) given to anesthetized cats resulted in dose related increases in heart rate (up to 70 beats/min) and blood pressure (up to 80 mm Hg). The pressor response was blocked by pretreatment of the animals with phentolamine; pretreatment for 3 days with 6-hydroxdopamine; with mecamylamine and spinal transection between C1 and C2 but not by propranolol or adrenalectomy. The increase in heart rate was blocked by pretreatment with propranolol, 6-hydroxydopamine, mecamylamine and spinal transection whereas adrenalectomy only affected the response slightly. DBO produced only negative effects on the isolated rabbit heart. Bioassay of arterial blood showed an increased level of circulating catecholamines corresponding to the cardiovascular stimulation. DBO had no tyramine-like activity on the isolated rabbit aortic strip but slightly potentiated the contraction induced by noradrenaline. These findings strongly suggest that the cardiovascular effects resulted from central stimulation of the sympathetic nervous system. A minor part of the observed sympathomimetic effects may also be the result of the ability of DBO to potentiate the effects of noradrenaline perhaps by blocking catecholamine uptake.

  8. Radioautographic study of the synthesis and migration of glycoproteins in the cells of the rat adrenal medulla

    International Nuclear Information System (INIS)

    Benchimol, Sarita; Cantin, Marc

    1978-01-01

    Rats were injected intravenously with ( 3 H) fucose to study the synthesis and migration of glycoproteins into adrenaline-storing and noradrenaline-storing cells of the adrenal medulla and to evaluate the fate of this radioactive sugar in both serum and adrenal-medulla at various time intervals. Radioactivity was decreased in serum by 50% between 5 and 20 min after the injection and by a hundred fold with 1 h. There was a sharp decrease in the radioactivity of the adrenal-medulla between 5 and 20 min after the injection and a slight, continuous decrease thereafter. The adrenal-medullae were fixed 5 min, 20 min, 1 h and 4 h after intravenous injection of [ 3 H] fucose, and radiautographs were analysed quantitatively after development in Microdol X. Kinetic analysis showed that, in both cell types, glycoprotein synthesis is completed in the Golgi complex and glycoproteins migrate subsequently to the secretory granules and to the cell coat. This analysis also revealed that [ 3 H] fucose moves much more rapidly in the Golgi complex of noradrenaline-storing cells than in that of adrenaline-storing cells and appears much earlier in the secretory granules of the former cell type [fr

  9. Cilnidipine lowered psychological stress-induced increase in blood pressure in a hypertensive man: a case report

    Directory of Open Access Journals (Sweden)

    Tsuji Sadatoshi

    2007-09-01

    Full Text Available Abstract Background In some hypertensive patients, psychological stress makes blood pressure difficult to control and causes physical symptoms such as headache or dizziness. We report the case of a hypertensive man whose psychological stress-induced increase in blood pressure was attenuated by cilnidipine. Case Presentation The patient (a 72-year-old man had hypertension and was on antihypertensive therapy. When mentally concentrating, he experienced occipital headaches and dizziness, and despite thorough testing, no abnormality was found. He was subsequently referred to our department. The mirror drawing test (MDT, a psychological stress test, increased blood pressure by about 40 mmHg, and the patient described occipital headache. Plasma noradrenaline level also increased from 212 to 548 pg/ml. We therefore switched the patient from nifedipine, an L-type calcium (Ca channel blocker, to cilnidipine, an L-type/N-type Ca channel blocker with suppressive effects on sympathetic activity. Cilnipidine attenuated MDT-induced an increase in blood pressure and plasma noradrenaline level and prevented the development of headache during testing. Conclusion These findings suggest that cilnidipine is a useful antihypertensive agent for hypertensive patients in whom psychological stress causes marked fluctuations in blood pressure.

  10. Synthesis of organic substances labelled with 14C and 35S

    International Nuclear Information System (INIS)

    Pichat, L.

    1958-01-01

    After a brief history of the development of the Section des Molecules marquees of the French Atomic Energy Commission, the author gives an outline of the synthesis of the following labelled compounds: benzene 14 C-6; phenyl-p-fluorophenyl, thienyl-2 β alanines β 14 C; noradrenaline β 14 C (arterenol β 14 C), dotriacontane 14 C-16-17, aminoethane sulfinic acid (hypotaurine 35 S). (author) [fr

  11. Biomarkers of Fatigue: Metabolomics Profiles Predictive of Cognitive Performance

    Science.gov (United States)

    2013-05-01

    Bin boundaries were then manually adjusted to further mitigate peak misalignment, and to keep known J-coupled multiplets within that same bin (e.g...synthesis of dopamine, noradrenaline, adrenaline, and serotonin. 5- HTP , 5-Hydroxytryptophan; PNMT, phenylethanolamine-N-methyl transferase; MAO...be taken when considering the interpretation of the current study results due to the low sample size (N-value) commonly seen with these types of

  12. Chronic oral nicotine increases brain [3H]epibatidine binding and responsiveness to antidepressant drugs, but not nicotine, in the mouse forced swim test

    DEFF Research Database (Denmark)

    Andreasen T., Jesper; Nielsen, Elsebet O; Redrobe, John P

    2009-01-01

    Smoking rates among depressed individuals is higher than among healthy subjects, and nicotine alleviates depressive symptoms. Nicotine increases serotonergic and noradrenergic neuronal activity and facilitates serotonin and noradrenaline release. In mice, acute nicotine administration enhances...... the activity of antidepressants in the mouse forced swim (mFST) and tail suspension tests. Here, we investigated if this action of nicotine is also reflected in a chronic treatment regimen....

  13. Endocrine and Metabolic Changes during Exhaustive Multifactorial Military Stress. Results from Studies during the Ranger Training Course of the Norwegian Military Academy

    Science.gov (United States)

    2001-03-01

    effect is due to secondary mechanisms. In the brain, noradrenaline serves as neurotransmitter for the neurones in the locus coeruleus, which have a...stimulates energy mobilization at many levels. First of all cortisol stimulates gluconeogenesis through the stimulation of relevant hepatic enzyme...behaviour, mood, neuronal excitability and electrical activity. Behavioural changes are observed both in excess states such as Cushing’s disease and

  14. Cooperative regulation of non-small cell lung carcinoma by nicotinic and beta-adrenergic receptors: a novel target for intervention.

    Directory of Open Access Journals (Sweden)

    Hussein A N Al-Wadei

    Full Text Available Lung cancer is the leading cause of cancer death; 80-85% of lung cancer cases are non-small cell lung cancer (NSCLC. Smoking is a documented risk factor for the development of this cancer. Although nicotine does not have the ability to initiate carcinogenic events, recent studies have implicated nicotine in growth stimulation of NSCLC. Using three NSCLC cell lines (NCI-H322, NCI-H441 and NCI-H1299, we identified the cooperation of nicotinic acetylcholine receptors (nAChRs and β-adrenergic receptors (β-ARs as principal regulators of these effects. Proliferation was measured by thymidine incorporation and MTT assays, and Western blots were used to monitor the upregulation of the nAChRs and activation of signaling molecules. Noradrenaline and GABA were measured by immunoassays. Nicotine-treated NSCLC cells showed significant induction of the α7nAChR and α4nAChR, along with significant inductions of p-CREB and p-ERK1/2 accompanied by increases in the stress neurotransmitter noradrenaline, which in turn led to the observed increase in DNA synthesis and cell proliferation. Effects on cell proliferation and signaling proteins were reversed by the α7nAChR antagonist α-BTX or the β-blocker propranolol. Nicotine treatment also down-regulated expression of the GABA synthesizing enzyme GAD 65 and the level of endogenous GABA, while treatment of NSCLC cells with GABA inhibited cell proliferation. Interestingly, GABA acts by reducing β-adrenergic activated cAMP signaling. Our findings suggest that nicotine-induced activation of this autocrine noradrenaline-initiated signaling cascade and concomitant deficiency in inhibitory GABA, similar to modulation of these neurotransmitters in the nicotine-addicted brain, may contribute to the development of NSCLC in smokers. Our data suggest that exposure to nicotine either by tobacco smoke or nicotine supplements facilitates growth and progression of NSCLC and that pharmacological intervention by β blocker may

  15. PDE3, but not PDE4, reduces β1- and β2-adrenoceptor-mediated inotropic and lusitropic effects in failing ventricle from metoprolol-treated patients

    Science.gov (United States)

    Molenaar, Peter; Christ, Torsten; Hussain, Rizwan I; Engel, Andreas; Berk, Emanuel; Gillette, Katherine T; Chen, Lu; Galindo-Tovar, Alejandro; Krobert, Kurt A; Ravens, Ursula; Levy, Finn Olav; Kaumann, Alberto J

    2013-01-01

    Background and Purpose PDE3 and/or PDE4 control ventricular effects of catecholamines in several species but their relative effects in failing human ventricle are unknown. We investigated whether the PDE3-selective inhibitor cilostamide (0.3–1 μM) or PDE4 inhibitor rolipram (1–10 μM) modified the positive inotropic and lusitropic effects of catecholamines in human failing myocardium. Experimental Approach Right and left ventricular trabeculae from freshly explanted hearts of 5 non-β-blocker-treated and 15 metoprolol-treated patients with terminal heart failure were paced to contract at 1 Hz. The effects of (-)-noradrenaline, mediated through β1 adrenoceptors (β2 adrenoceptors blocked with ICI118551), and (-)-adrenaline, mediated through β2 adrenoceptors (β1 adrenoceptors blocked with CGP20712A), were assessed in the absence and presence of PDE inhibitors. Catecholamine potencies were estimated from –logEC50s. Key Results Cilostamide did not significantly potentiate the inotropic effects of the catecholamines in non-β-blocker-treated patients. Cilostamide caused greater potentiation (P = 0.037) of the positive inotropic effects of (-)-adrenaline (0.78 ± 0.12 log units) than (-)-noradrenaline (0.47 ± 0.12 log units) in metoprolol-treated patients. Lusitropic effects of the catecholamines were also potentiated by cilostamide. Rolipram did not affect the inotropic and lusitropic potencies of (-)-noradrenaline or (-)-adrenaline on right and left ventricular trabeculae from metoprolol-treated patients. Conclusions and Implications Metoprolol induces a control by PDE3 of ventricular effects mediated through both β1 and β2 adrenoceptors, thereby further reducing sympathetic cardiostimulation in patients with terminal heart failure. Concurrent therapy with a PDE3 blocker and metoprolol could conceivably facilitate cardiostimulation evoked by adrenaline through β2 adrenoceptors. PDE4 does not appear to reduce inotropic and lusitropic effects of

  16. Stress hormones promote growth of B16-F10 melanoma metastases: an interleukin 6- and glutathione-dependent mechanism.

    Science.gov (United States)

    Valles, Soraya L; Benlloch, María; Rodriguez, María L; Mena, Salvador; Pellicer, José A; Asensi, Miguel; Obrador, Elena; Estrela, José M

    2013-03-22

    Interleukin (IL)-6 (mainly of tumor origin) activates glutathione (GSH) release from hepatocytes and its interorgan transport to B16-F10 melanoma metastatic foci. We studied if this capacity to overproduce IL-6 is regulated by cancer cell-independent mechanisms. Murine B16-F10 melanoma cells were cultured, transfected with red fluorescent protein, injected i.v. into syngenic C57BL/6J mice to generate lung and liver metastases, and isolated from metastatic foci using high-performance cell sorting. Stress hormones and IL-6 levels were measured by ELISA, and CRH expression in the brain by in situ hybridization. DNA binding activity of NF-κB, CREB, AP-1, and NF-IL-6 was measured using specific transcription factor assay kits. IL-6 expression was measured by RT-PCR, and silencing was achieved by transfection of anti-IL-6 small interfering RNA. GSH was determined by HPLC. Cell death analysis was distinguished using fluorescence microscopy, TUNEL labeling, and flow cytometry techniques. Statistical analyses were performed using Student's t test. Plasma levels of stress-related hormones (adrenocorticotropin hormone, corticosterone, and noradrenaline) increased, following a circadian pattern and as compared to non-tumor controls, in mice bearing B16-F10 lung or liver metastases. Corticosterone and noradrenaline, at pathophysiological levels, increased expression and secretion of IL-6 in B16-F10 cells in vitro. Corticosterone- and noradrenaline-induced transcriptional up-regulation of IL-6 gene involves changes in the DNA binding activity of nuclear factor-κB, cAMP response element-binding protein, activator protein-1, and nuclear factor for IL-6. In vivo inoculation of B16-F10 cells transfected with anti-IL-6-siRNA, treatment with a glucocorticoid receptor blocker (RU-486) or with a β-adrenoceptor blocker (propranolol), increased hepatic GSH whereas decreased plasma IL-6 levels and metastatic growth. Corticosterone, but not NORA, also induced apoptotic cell death in

  17. A psychopharmacological aspects of human emotional memory for emotional material.

    OpenAIRE

    Brignell, C. M.

    2004-01-01

    It is often assumed that emotional events are remembered in great clarity and detail. This thesis begins with a review of the literature on memory enhancement by emotional material. This enhancement may involve mechanisms that are psychologically and neurobiologically distinct from the mechanisms usually employed in memory for neutral material, such as modulation of consolidation by emotional arousal via noradrenaline action in the amygdala. Theoretically, pharmacological manipulation of nora...

  18. [The catecholamine content of the hypothalamus during the modelling of the ulcer process in the gastroduodenal area].

    Science.gov (United States)

    Iemel'ianenko, I V; Sultanova, I D; Voronych, N M

    1995-01-01

    The content of catecholamines in rat hypothalamus in experimental ulcer process in gastroduodenal region has been studied in experiments on rats. It was determined that under these conditions the content of hypothalamus adrenalin increases and the content of noradrenalin decreases. The level of dofamin and DOFA in this brain structure changes in phases. The mentioned shifts depended on the duration and character of the pathological process in the gastroduodenal region.

  19. Inhibition of reflex vagal bradycardia by a central action of 5-hydroxytryptophan.

    OpenAIRE

    Tadepalli, A. S.

    1980-01-01

    1 Vagally mediated reflex bradycardia was elicited in spinal cats with intravenous pressor doses of noradrenaline. Administration of 5-hydroxytryptophan (1.5 and 3 mg total dose) into the fourth cerebral ventricle reduced the reflex bradycardia. 2 Inhibition of central amino acid decarboxylase with R044602 prevented the effects of 5-hydroxytryptophan. After intravenous administration of 5-hydroxytryptophan, vagal reflex bradycardia was not affected. 3 Results suggest that 5-hydroxytryptophan ...

  20. Photochemical decomposition of catecholamines

    International Nuclear Information System (INIS)

    Mol, N.J. de; Henegouwen, G.M.J.B. van; Gerritsma, K.W.

    1979-01-01

    During photochemical decomposition (lambda=254 nm) adrenaline, isoprenaline and noradrenaline in aqueous solution were converted to the corresponding aminochrome for 65, 56 and 35% respectively. In determining this conversion, photochemical instability of the aminochromes was taken into account. Irradiations were performed in such dilute solutions that the neglect of the inner filter effect is permissible. Furthermore, quantum yields for the decomposition of the aminochromes in aqueous solution are given. (Author)

  1. Apathy and noradrenaline: silent partners to mild cognitive impairment in Parkinson's disease?

    OpenAIRE

    Loued-Khenissi Leyla; Preuschoff Kerstin

    2015-01-01

    PURPOSE OF REVIEW: Mild cognitive impairment (MCI) is a comorbid factor in Parkinson's disease. The aim of this review is to examine the recent neuroimaging findings in the search for Parkinson's disease MCI (PD MCI) biomarkers to gain insight on whether MCI and specific cognitive deficits in Parkinson's disease implicate striatal dopamine or another system. RECENT FINDINGS: The evidence implicates a diffuse pathophysiology in PD MCI rather than acute dopaminergic involvement. On the one han...

  2. Determination of plasma adrenaline and noradrenaline levels with the Cat-a-Kit

    International Nuclear Information System (INIS)

    Nel, P.B.; Du Preez, S.E.

    1980-01-01

    A method for the determination of catecholamines (Cat-a-Kit; Upjohn Diagnostics) is discussed. It depends upon the enzymatic conversion of the catecholamines to their ring o-methylated analogues in the presence of s-adenosyl-L-methionine-methyl- 14 C and catechol-o-methyltransferase. Values obtained from the blood plasma of 16 tetraplegic and 11 healthy volunteers are reported. The advantages and disadvantages of the Cat-a-Kit are discussed

  3. Stress hormone epinephrine (adrenaline) and norepinephrine (noradrenaline) effects on the anaerobic bacteria.

    Science.gov (United States)

    Boyanova, Lyudmila

    2017-04-01

    Microbial endocrinology is a relatively new research area that already encompasses the anaerobes. Stress hormones, epinephrine and norepinephrine, can affect the growth of anaerobic bacteria such as Fusobacterium nucleatum, Prevotella spp., Porhyromonas spp., Tanerella forsythia and Propionibacterium acnes and can increase virulence gene expression, iron acquisition and many virulence factors of some anaerobic species such as Clostridium perfringens, Porphyromonas gingivalis and Brachyspira pilosicoli. Epinephrine and norepinephrine effects can lead to a growth increase or decrease, or no effect on the growth of the anaerobes. The effects are species-specific and perhaps strain-specific. Discrepancies in the results of some studies can be due to the different methods and media used, catecholamine concentrations, measurement techniques and the low number of strains tested. Biological effects of the stress hormones on the anaerobes may range from halitosis and a worsening of periodontal diseases to tissue damages and atherosclerotic plaque ruptures. Optimizations of the research methods and a detailed assessment of the catecholamine effects in conditions mimicking those in affected organs and tissues, as well as the effects on the quorum sensing and virulence of the anaerobes and the full spectrum of biological consequences of the effects are interesting topics for further evaluation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Neuroendocrine tumors of the adrenal glands

    International Nuclear Information System (INIS)

    Antova, R.; Valcheva, V.; Genova, K.

    2013-01-01

    Full text: Introduction: Paraganglioma is neuroendocrine neoplasm derived from the sympathetic and parasympathetic paraganglia. They produce large amounts of catecholamine, usually noradrenaline and adrenaline. In 10% of cases are malignant, the criterion for which is not local tumor invasion, and the presence of distant metastases. What you will learn: We present a case of 17 years old boy with headache in the occipital region. Measured blood pressure is 200/100. Patient was consulted by children cardiologist and Holter examination was conducted and a high arterial hypertension (AH) with maximum values to 217/120 mmHg, was recognized with a pattern corresponding to secondary hypertension. An antihypertensive therapy with two drugs has started. Laboratory indicators showed enhanced levels of catecholamines in the urine, enhanced serum levels of noradrenaline, dopamine, renin, adosteron. Doppler ultrasound of the renal arteries showed evidence of stenosis of the left renal artery. Discussion: The performed CT abdomen with contrast enhancement demonstrated retroperitoneal heterogeneous, well- vascularized with lobular surface tumor formation, located between the left renal artery, as the latter ones are in varying degrees stenosed. It was considered that this was a paraganglioma. The diagnosis was confirmed postoperatively. Conclusion: CT is a diagnostic non-invasive imaging method serving for preoperative evaluation of tumors of the sympathetic and parasympathetic paraganglia

  5. Peripheral vascular effects of bretylium tosylate in man.

    Science.gov (United States)

    Blair, D A; Glover, W E; Kidd, B S; Roddie, I C

    1960-09-01

    After intra-arterial infusion of bretylium tosylate (12.5 mg.), the reflex changes in vasoconstrictor tone which normally occur in the forearm with body cooling, positive pressure breathing, the Valsalva manoeuvre and postural change were greatly reduced or abolished. Reflex vasodilatation mediated by cholinergic fibres in response to body heating or to emotional stress was little affected. It was concluded that bretylium can selectively block the activity of sympathetic noradrenergic fibres without causing a similar block of sympathetic cholinergic fibres. As the responses to intravenous or intra-arterial infusions of adrenaline or noradrenaline were not reduced after bretylium, it was concluded that bretylium interferes with the activity of noradrenergic fibres rather than with the activity of the noradrenaline released at the nerve ending. After bretylium infusion, forearm and hand blood flow did not often rise to levels characteristic of full release of vasoconstrictor tone. As infusion of bretylium into a nerve-blocked forearm resulted in a pronounced reduction in flow, it is concluded that bretylium also has a constrictor effect on blood vessels. The state of the vessels following an infusion of bretylium appears to depend on the balance between this constrictor action and the longer-acting sympathetic blocking effect.

  6. Neuronal basis of innate olfactory attraction to ethanol in Drosophila.

    Directory of Open Access Journals (Sweden)

    Andrea Schneider

    Full Text Available The decision to move towards a mating partner or a food source is essential for life. The mechanisms underlying these behaviors are not well understood. Here, we investigated the role of octopamine - the invertebrate analogue of noradrenaline - in innate olfactory attraction to ethanol. We confirmed that preference is caused via an olfactory stimulus by dissecting the function of the olfactory co-receptor Orco (formally known as OR83b. Orco function is not required for ethanol recognition per se, however it plays a role in context dependent recognition of ethanol. Odor-evoked ethanol preference requires the function of Tbh (Tyramine β hydroxalyse, the rate-limiting enzyme of octopamine synthesis. In addition, neuronal activity in a subset of octopaminergic neurons is necessary for olfactory ethanol preference. Notably, a specific neuronal activation pattern of tyraminergic/octopaminergic neurons elicit preference and is therefore sufficient to induce preference. In contrast, dopamine dependent increase in locomotor activity is not sufficient for olfactory ethanol preference. Consistent with the role of noradrenaline in mammalian drug induced rewards, we provide evidence that in adult Drosophila the octopaminergic neurotransmitter functions as a reinforcer and that the molecular dissection of the innate attraction to ethanol uncovers the basic properties of a response selection system.

  7. The effects of chronic resveratrol treatment on vascular responsiveness of streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Silan, Coskun

    2008-05-01

    Deficiency in the vasorelaxant capacity is a result of an oxidative stress in diabetic animals and seems to be an etiological factor of vascular complications of diabetes. The present study was designed to examine whether resveratrol (RSV), a polyphenolic compound which is naturally present in grape and red wine, has a protective effect on diabetic aorta. Resveratrol (5 mg/kg/d, i.p.) was administered for 42 d to streptozotocin (STZ) (60 mg/kg) induced diabetic rats. Loss of weight, hyperglycemia, and elevated levels of plasma malondialdehyde (MDA) were observed in diabetic rats. Resveratrol treatment was significantly effective for these metabolic and biochemical abnormalities. The contractile responses of the aorta were recorded. Compared with control subjects, the aorta showed significantly enhanced contractile responses to noradrenaline (NA), but not to potassium chloride (KCl), in diabetic rats. Treatment of diabetic rats with resveratrol significantly reversed the increases in responsiveness and sensitivity of aorta to noradrenaline. In diabetic aorta, the relaxation response to acetylcholine (Ach) was found to be significantly decreased compared with control subjects, and resveratrol treatment reversed this; no such change was observed in the relaxation response to sodium nitroprusside (SNP). These results indicated that resveratrol significantly improved not only glucose metabolism and oxidative injury but also impaired vascular responses in streptozotocin induced diabetic rats.

  8. Effects of Electromagnetic Radiation Exposure on Stress-Related Behaviors and Stress Hormones in Male Wistar Rats

    Science.gov (United States)

    Mahdavi, Seyed Mohammad; Sahraei, Hedayat; Yaghmaei, Parichehreh; Tavakoli, Hassan

    2014-01-01

    Studies have demonstrated that electromagnetic waves, as the one of the most important physical factors, may alter cognitive and non-cognitive behaviors, depending on the frequency and energy. Moreover, non-ionizing radiation of low energy waves e.g. very low frequency waves could alter this phenomenon via alterations in neurotransmitters and neurohormones. In this study, short, medium, and long-term exposure to the extremely low frequency electromagnetic field (ELF-EMF) (1 and 5 Hz radiation) on behavioral, hormonal, and metabolic changes in male Wistar rats (250 g) were studied. In addition, changes in plasma concentrations for two main stress hormones, noradrenaline and adrenocorticotropic hormone (ACTH) were evaluated. ELF-EMF exposure did not alter body weight, and food and water intake. Plasma glucose level was increased and decreased in the groups which exposed to the 5 and 1Hz wave, respectively. Plasma ACTH concentration increased in both using frequencies, whereas nor-adrenaline concentration showed overall reduction. At last, numbers of rearing, sniffing, locomotor activity was increased in group receiving 5 Hz wave over the time. In conclusions, these data showed that the effects of 1 and 5 Hz on the hormonal, metabolic and stress-like behaviors may be different. Moreover, the influence of waves on stress system is depending on time of exposure. PMID:25489427

  9. Mild prenatal protein malnutrition increases alpha2C-adrenoceptor density in the cerebral cortex during postnatal life and impairs neocortical long-term potentiation and visuo-spatial performance in rats.

    Science.gov (United States)

    Soto-Moyano, Rubén; Valladares, Luis; Sierralta, Walter; Pérez, Hernán; Mondaca, Mauricio; Fernández, Victor; Burgos, Héctor; Hernández, Alejandro

    2005-06-01

    Mild reduction in the protein content of the mother's diet from 25 to 8% casein, calorically compensated by carbohydrates, does not alter body and brain weights of rat pups at birth, but leads to significant enhancements in the concentration and release of cortical noradrenaline during early postnatal life. Since central noradrenaline and some of its receptors are critically involved in long-term potentiation (LTP) and memory formation, this study evaluated the effect of mild prenatal protein malnutrition on the alpha2C-adrenoceptor density in the frontal and occipital cortices, induction of LTP in the same cortical regions and the visuo-spatial memory. Pups born from rats fed a 25% casein diet throughout pregnancy served as controls. At day 8 of postnatal age, prenatally malnourished rats showed a threefold increase in neocortical alpha2C-adrenoceptor density. At 60 days-of-age, alpha2C-adrenoceptor density was still elevated in the neocortex, and the animals were unable to maintain neocortical LTP and presented lower visuo-spatial memory performance. Results suggest that overexpression of neocortical alpha2C-adrenoceptors during postnatal life, subsequent to mild prenatal protein malnutrition, could functionally affect the synaptic networks subserving neocortical LTP and visuo-spatial memory formation.

  10. EPR studies of chromium(V) intermediates generated via reduction of chromium(VI) by DOPA and related catecholamines

    DEFF Research Database (Denmark)

    Pattison, D I; Lay, P A; Davies, Michael Jonathan

    2000-01-01

    The reductions of K2Cr2O7 by catecholamines, DOPA, DOPA-beta,beta-d2, N-acetyl-DOPA, alpha-methyl-DOPA, dopamine, adrenaline, noradrenaline, catechol, 1,2-dihydroxybenzoic acid (DHBA), and 4-tert-butylcatechol (TBC), produce a number of Cr(V) electron paramagnetic resonance (EPR) signals. These s......The reductions of K2Cr2O7 by catecholamines, DOPA, DOPA-beta,beta-d2, N-acetyl-DOPA, alpha-methyl-DOPA, dopamine, adrenaline, noradrenaline, catechol, 1,2-dihydroxybenzoic acid (DHBA), and 4-tert-butylcatechol (TBC), produce a number of Cr(V) electron paramagnetic resonance (EPR) signals...... deuteration or enrichment with 15N), and simulation of the signals, show that the superhyperfine couplings originate from the side chain protons, confirming that the catecholamine ligands are cyclized. At pH 3.5, a major short-lived EPR signal is observed for many of the substrates at g(iso) approximately 1......) species with a sixth ligand (e.g. H2O). Addition of catalase or deoxygenation of the solutions did not affect the main EPR signals. When the substrates were in excess (pH > 4.5), primary and secondary (cyclized) semiquinones were also detected. Semiquinone stabilization by Zn(II) complexation yielded...

  11. Neuroendocrine response to film-induced sexual arousal in men and women.

    Science.gov (United States)

    Exton, N G; Truong, T C; Exton, M S; Wingenfeld, S A; Leygraf, N; Saller, B; Hartmann, U; Schedlowski, M

    2000-02-01

    The psychoneuroendocrine responses to sexual arousal have not been clearly established in humans. However, we have demonstrated previously that masturbation-induced orgasm stimulates cardiovascular activity and induces increases in catecholamines and prolactin in blood of both males and females. We presently investigated the role of orgasm in producing these effects. Therefore, in this study parallel analysis of prolactin, adrenaline, noradrenaline, and cortisol concentrations, together with cardiovascular variables of systolic/diastolic blood pressure and heart rate were undertaken during film-induced sexual arousal in nine healthy adult men and nine healthy adult women. Blood was drawn continuously via an indwelling cannula and connected tubing system passed through a mini-pump. In parallel, the cardiovascular parameters were recorded continuously via a computerised finger-cuff sensor. Subjective sexual arousal increased significantly in both men and women during the erotic film, with sexual arousal eliciting an increase in blood pressure in both males and females, and plasma noradrenaline in females only. In contrast, adrenaline, cortisol and prolactin levels were unaffected by sexual arousal. These data further consolidate the role of sympathetic activation in sexual arousal processes. Furthermore, they demonstrate that increases in plasma prolactin during sexual stimulation are orgasm-dependent, suggesting that prolactin may regulate a negative-feedback sexual-satiation mechanism.

  12. Polymorphisms of serotonin receptor 2A and 2C genes and COMT in relation to obesity and type 2 diabetes

    DEFF Research Database (Denmark)

    Kring, Sofia I I; Werge, Thomas; Holst, Claus

    2009-01-01

    BACKGROUND: Candidate genes of psychological importance include 5HT2A, 5HT2C, and COMT, implicated in the serotonin, noradrenaline and dopamine pathways, which also may be involved in regulation of energy balance. We investigated the associations of single nucleotide polymorphisms (SNPs) of these......BACKGROUND: Candidate genes of psychological importance include 5HT2A, 5HT2C, and COMT, implicated in the serotonin, noradrenaline and dopamine pathways, which also may be involved in regulation of energy balance. We investigated the associations of single nucleotide polymorphisms (SNPs......) of these genes with obesity and metabolic traits. METHODOLOGY/PRINCIPAL FINDINGS: In a population of 166 200 young men examined at the draft boards, obese men (n = 726, BMI> or =31.0 kg/m(2)) and a randomly selected group (n = 831) were re-examined at two surveys at mean ages 46 and 49 years (S-46, S-49......). Anthropometric, physiological and biochemical measures were available. Logistic regression analyses were used to assess age-adjusted odds ratios. No significant associations were observed of 5HT2A rs6311, 5HT2C rs3813929 and COMT rs4680 with obesity, except that COMT rs4680 GG-genotype was associated with fat...

  13. Phosphatidic acid accumulation and catecholamine release in adrenal chromaffin cells: stimulation by high potassium and by nicotine, and effect of a diacylglycerol kinase inhibitor R 59 022.

    Science.gov (United States)

    Owen, P J; Jones, J A; Boarder, M R

    1991-09-01

    Using primary cultures of bovine adrenal chromaffin cells labelled with 32Pi, we show that stimulation with bradykinin, nicotine, or a depolarising concentration of potassium stimulates the accumulation of [32P]phosphatidic acid. The effects of nicotine and potassium are smaller than the effect of bradykinin, and are dependent entirely on extracellular calcium. The diacylglycerol kinase inhibitor R 59 022 attenuates the formation of phosphatidic acid by nicotine and depolarising concentrations of potassium. This inhibitor also blocks the nicotine and potassium stimulation of noradrenaline release from chromaffin cells. Using 45Ca2+ influx studies, we show that the nicotine-evoked calcium influx is also attenuated by R 59 022. These observations contrast with those in another report in which we showed that bradykinin stimulation of either [32P]phosphatidic acid accumulation or noradrenaline release is not affected by R 59 022. It is likely that the calcium influx produced by nicotine and depolarising potassium is blocked by R 59 022 by a mechanism that is independent of its ability to block diacylglycerol kinase. The nicotine- and potassium-stimulated [32P]phosphatidic acid accumulation is a consequence of this calcium influx and presumably reflects calcium activation of either phospholipase C or phospholipase D.

  14. Effects of hirsutine, an antihypertensive indole alkaloid from Uncaria rhynchophylla, on intracellular calcium in rat thoracic aorta.

    Science.gov (United States)

    Horie, S; Yano, S; Aimi, N; Sakai, S; Watanabe, K

    1992-01-01

    The effects of hirsutine, an indole alkaloid from Uncaria rhynchophylla (MIQ.) Jackson, on cytosolic Ca2+ level ([Ca2+]cyt) were studied by using fura-2-Ca2+ fluorescence in smooth muscle of the isolated rat aorta. Noradrenaline and high K+ solution produced a sustained increase in [Ca2+]cyt. Application of hirsutine after the increases in [Ca2+]cyt induced by noradrenaline and high K+ notably decreased [Ca2+]cyt, suggesting that hirsutine inhibits Ca2+ influx mainly through a voltage-dependent Ca2+ channel. Furthermore, the effect of hirsutine on intracellular Ca2+ store was studied by using contractile responses to caffeine under the Ca(2+)-free nutrient condition in the rat aorta. When hirsutine was added at 30 microM before caffeine treatment, the agent slightly but significantly reduced the caffeine-induced contraction. When added during Ca2+ loading, hirsutine definitely augmented the contractile response to caffeine. These results suggest that hirsutine inhibits Ca2+ release from the Ca2+ store and increases Ca2+ uptake into the Ca2+ store, leading to a reduction of intracellular Ca2+ level. It is concluded that hirsutine reduces intracellular Ca2+ level through its effect on the Ca2+ store as well as through its effect on the voltage-dependent Ca2+ channel.

  15. Effects of electromagnetic radiation exposure on stress-related behaviors and stress hormones in male wistar rats.

    Science.gov (United States)

    Mahdavi, Seyed Mohammad; Sahraei, Hedayat; Yaghmaei, Parichehreh; Tavakoli, Hassan

    2014-11-01

    Studies have demonstrated that electromagnetic waves, as the one of the most important physical factors, may alter cognitive and non-cognitive behaviors, depending on the frequency and energy. Moreover, non-ionizing radiation of low energy waves e.g. very low frequency waves could alter this phenomenon via alterations in neurotransmitters and neurohormones. In this study, short, medium, and long-term exposure to the extremely low frequency electromagnetic field (ELF-EMF) (1 and 5 Hz radiation) on behavioral, hormonal, and metabolic changes in male Wistar rats (250 g) were studied. In addition, changes in plasma concentrations for two main stress hormones, noradrenaline and adrenocorticotropic hormone (ACTH) were evaluated. ELF-EMF exposure did not alter body weight, and food and water intake. Plasma glucose level was increased and decreased in the groups which exposed to the 5 and 1Hz wave, respectively. Plasma ACTH concentration increased in both using frequencies, whereas nor-adrenaline concentration showed overall reduction. At last, numbers of rearing, sniffing, locomotor activity was increased in group receiving 5 Hz wave over the time. In conclusions, these data showed that the effects of 1 and 5 Hz on the hormonal, metabolic and stress-like behaviors may be different. Moreover, the influence of waves on stress system is depending on time of exposure.

  16. Pharmacological Fingerprints of Contextual Uncertainty.

    Directory of Open Access Journals (Sweden)

    Louise Marshall

    2016-11-01

    Full Text Available Successful interaction with the environment requires flexible updating of our beliefs about the world. By estimating the likelihood of future events, it is possible to prepare appropriate actions in advance and execute fast, accurate motor responses. According to theoretical proposals, agents track the variability arising from changing environments by computing various forms of uncertainty. Several neuromodulators have been linked to uncertainty signalling, but comprehensive empirical characterisation of their relative contributions to perceptual belief updating, and to the selection of motor responses, is lacking. Here we assess the roles of noradrenaline, acetylcholine, and dopamine within a single, unified computational framework of uncertainty. Using pharmacological interventions in a sample of 128 healthy human volunteers and a hierarchical Bayesian learning model, we characterise the influences of noradrenergic, cholinergic, and dopaminergic receptor antagonism on individual computations of uncertainty during a probabilistic serial reaction time task. We propose that noradrenaline influences learning of uncertain events arising from unexpected changes in the environment. In contrast, acetylcholine balances attribution of uncertainty to chance fluctuations within an environmental context, defined by a stable set of probabilistic associations, or to gross environmental violations following a contextual switch. Dopamine supports the use of uncertainty representations to engender fast, adaptive responses.

  17. Plasma catecholamine and corticosterone responses to predictable and unpredictable noise stress in rats

    OpenAIRE

    Van der Gugten, J; Slangen, J L; de Boer, S.F.

    1989-01-01

    Plasma noradrenaline (NA), adrenaline (A) and corticosterone (CS) increases were determined in individual rats subjected to either 20 regularly or irregularly scheduled white-noise stimulations (4 min, 100 dBA). Blood was frequently sampled during the first and twentieth noise exposure, and during a reexposure after 24 hr. During the sampling periods, behavioral activities of the rats were recorded. The initial noise-induced CS release was partially reduced following the regular noise present...

  18. The effect of experimental diabetes on phenylalanine metabolism in isolated liver cells.

    OpenAIRE

    Santana, M A; Fisher, M J; Bate, A J; Pogson, C I

    1985-01-01

    Chronic (10-day) diabetes was associated with increased metabolic flux through phenylalanine hydroxylase in isolated liver cells. This flux was stimulated by 0.1 microM-glucagon, but not by 10 microM-noradrenaline; 0.1 microM-insulin affected neither basal nor glucagon-stimulated flux. The increased rate of phenylalanine hydroxylation in diabetes was accompanied by parallel increases in enzyme activity (as measured with artificial cofactor) and immunoreactive-enzyme-protein content. In contra...

  19. The cardiorespiratory effects of detomidine in the primate (Papio ursinus)

    OpenAIRE

    H. Bosman

    1990-01-01

    Detomidine is a novel imidazole derivative with a high affinity for a₂-adrenoceptors. The cardiorespiratory effects of this drug were evaluated in the primate (Papio ursinus) under ketamine anaesthesia. The release of noradrenalin is modulated by a₂-adrenoceptors, and this resulted in a longer duration of anaesthesia when ketamine was combined with detomidine in comparison with ketamine alone. Detomidine caused a marked bradycardia, which was not reflex induced, but probably the result of...

  20. The nature of catecholamine-containing neurons in the enteric nervous system in relationship with organogenesis, normal human anatomy and neurodegeneration.

    Science.gov (United States)

    Natale, G; Ryskalin, L; Busceti, C L; Biagioni, F; Fornai, F

    2017-09-01

    The gastrointestinal tract is provided with extrinsic and intrinsic innervation. The extrinsic innervation includes the classic vagal parasympathetic and sympathetic components, with afferent sensitive and efferent secretomotor fibers. The intrinsic innervations is represented by the enteric nervous system (ENS), which is recognized as a complex neural network controlling a variety of cell populations, including smooth muscle cells, mucosal secretory cells, endocrine cells, microvasculature, immune and inflammatory cells. This is finalized to regulate gastrointestinal secretion, absorption and motility. In particular, this network is organized in several plexuses each one providing quite autonomous control of gastrointestinal functions (hence the definition of "second brain"). The similarity between ENS and CNS is further substantiated by the presence of local sensitive pseudo- unipolar ganglionic neurons with both peripheral and central branching which terminate in the enteric wall. A large variety of neurons and neurotransmitters takes part in the ENS. However, the nature of these neurons and their role in the regulation of gastrointestinal functions is debatable. In particular, the available literature reporting the specific nature of catecholamine- containing neurons provides conflicting evidence. This is critical both for understanding the specific role of each catecholamine in the gut and, mostly, to characterize specifically the enteric neuropathology occurring in a variety of diseases. An emphasis is posed on neurodegenerative disorders, such as Parkinson's disease, which is associated with the loss of catecholamine neurons. In this respect, the recognition of the nature of such neurons within the ENS would contribute to elucidate the pathological mechanisms which produce both CNS and ENS degeneration and to achieve more effective therapeutic approaches. Despite a great emphasis is posed on the role of noradrenaline to regulate enteric activities only a few

  1. Anorexia nervosa depends on adrenal sympathetic hyperactivity: opposite neuroautonomic profile of hyperinsulinism syndrome

    Directory of Open Access Journals (Sweden)

    Lechin F

    2010-09-01

    Full Text Available Fuad Lechin1,2, Bertha van der Dijs1,2, Betty Pardey-Maldonado1, Jairo E Rivera1, Scarlet Baez1, Marcel E Lechin31Department of Pathophysiology, Sections of Neuroendocrinology, Neuropharmacology, and Neurochemistry, Instituto de Medicina Experimental, Faculty of Medicine, Universidad Central de Venezuela, Caracas; 2Instituto de Vias Digestivas Caracas, Centro Clínico Profesional, Caracas, Venezuela; 3Department of Internal Medicine, Texas A and M Health Science Center, College of Medicine, Texas, USAObjective: The aim of our study was to determine the central and peripheral autonomic nervous system profiles underlying anorexia nervosa (AN syndrome, given that affected patients present with the opposite clinical profile to that seen in the hyperinsulinism syndrome.Design: We measured blood pressure and heart rate, as well as circulating neurotransmitters (noradrenaline, adrenaline, dopamine, plasma serotonin, and platelet serotonin, using high-performance liquid chromatography with electrochemical detection, during supine resting, one minute of orthostasis, and after five minutes of exercise. In total, 22 AN patients (12 binge-eating/purging type and 10 restricting type and age-, gender-, and race-matched controls (70 ± 10.1% versus 98 ± 3.0% of ideal body weight were recruited.Results: We found that patients with AN had adrenal sympathetic overactivity and neural sympathetic underactivity, demonstrated by a predominance of circulating adrenaline over noradrenaline levels, not only during the supine resting state (52 ± 2 versus 29 ± 1 pg/mL but also during orthostasis (67 ± 3 versus 32 ± 2 pg/mL, P < 0.05 and after exercise challenge (84 ± 4 versus 30 ± 3 pg/mL, P < 0.01.Conclusion: Considering that this peripheral autonomic nervous system disorder depends on the absolute predominance of adrenomedullary C1 adrenergic nuclei over A5 noradrenergic pontine nucleus, let us ratify the abovementioned findings. The AN syndrome depends on the

  2. Sympathomimetic effects of Scoparia dulcis L. and catecholamines isolated from plant extracts.

    Science.gov (United States)

    Freire, S M; Torres, L M; Souccar, C; Lapa, A J

    1996-06-01

    The herb Scoparia dulcis L. is used in Brazilian folk medicine to treat bronchitis, gastric disorders, haemorrhoids, insect bites and skin wounds, and in oriental medicine to treat hypertension. A previous study has shown that extracts of S. dulcis have analgesic and anti-inflammatory properties; in this work the sympathomimetic activity of an ethanolic extract of Scoparia dulcis L. has been investigated in rodent preparations in-vivo and in-vitro. Administration of the extract (0.5-2 mg kg-1, i.v.) to anaesthetized rats produced dose-related hypertension blocked by the alpha-adrenoceptor antagonist prazosin (1 mg kg-1). Partition of the extract in chloroform-water yielded an aqueous phase 20 times more potent than the extract; this produced hypertension in either reserpine-treated or pithed rats. In untreated and reserpine-treated rats the same fraction (1-3 x 10(3) micrograms mL-1) produced concentration-dependent contractions of the vas deferens musculature parallel to those obtained with noradrenaline (10(-8)-10(-4)M). Prazosin (10(-7)M) reduced the maximum contractile effect of the aqueous fraction, and shifted the concentration-response curves for noradrenaline to the right. The aqueous fraction (25 and 50 micrograms mL-1) increased the inotropism of electrically driven left atria of rats, the effect being blocked by propranolol (0.4 microgram mL-1). In preparations of guinea-pig tracheal rings the aqueous fraction (1-3 x 10(3) micrograms mL-1) relaxed the muscle contraction induced by histamine (10(-4) M) in proportion to the concentration. The effect was antagonized competitively by propranolol (1.5 microM). High-performance liquid-chromatographic analysis of the aqueous fraction revealed the presence of both noradrenaline and adrenaline in the plant extract. The results indicated that both catecholamines may account for the hypertensive and inotropic effects obtained after parenteral administration of S. dulcis extracts. This sympathomimetic activity is

  3. In utero exposure to a low concentration of diesel exhaust affects spontaneous locomotor activity and monoaminergic system in male mice

    Directory of Open Access Journals (Sweden)

    Odagiri Takashi

    2010-03-01

    Full Text Available Abstract Background Epidemiological studies have suggested that suspended particulate matter (SPM causes detrimental health effects such as respiratory and cardiovascular diseases, and that diesel exhaust particles from automobiles is a major contributor to SPM. It has been reported that neonatal and adult exposure to diesel exhaust damages the central nervous system (CNS and induces behavioral alteration. Recently, we have focused on the effects of prenatal exposure to diesel exhaust on the CNS. In this study, we examined the effects of prenatal exposure to low concentration of diesel exhaust on behaviour and the monoaminergic neuron system. Spontaneous locomotor activity (SLA and monoamine levels in the CNS were assessed. Methods Mice were exposed prenatally to a low concentration of diesel exhaust (171 μg DEP/m3 for 8 hours/day on gestational days 2-16. SLA was assessed for 3 days in 4-week-old mice by analysis of the release of temperature-associated infrared rays. At 5 weeks of age, the mice were sacrificed and the brains were used for analysis by high-performance liquid chromatography (HPLC. Results and Discussion Mice exposed to a low concentration of diesel exhaust showed decreased SLA in the first 60 minutes of exposure. Over the entire test period, the mice exposed prenatally to diesel exhaust showed decreased daily SLA compared to that in control mice, and the SLA in each 3 hour period was decreased when the lights were turned on. Neurotransmitter levels, including dopamine and noradrenaline, were increased in the prefrontal cortex (PFC in the exposure group compared to the control group. The metabolites of dopamine and noradrenaline also increased in the PFC. Neurotransmitter turnover, an index of neuronal activity, of dopamine and noradrenaline was decreased in various regions of the CNS, including the striatum, in the exposure group. The serum corticosterone level was not different between groups. The data suggest that decreased

  4. Current real-life use of vasopressors and inotropes in cardiogenic shock - adrenaline use is associated with excess organ injury and mortality.

    Science.gov (United States)

    Tarvasmäki, Tuukka; Lassus, Johan; Varpula, Marjut; Sionis, Alessandro; Sund, Reijo; Køber, Lars; Spinar, Jindrich; Parissis, John; Banaszewski, Marek; Silva Cardoso, Jose; Carubelli, Valentina; Di Somma, Salvatore; Mebazaa, Alexandre; Harjola, Veli-Pekka

    2016-07-04

    Vasopressors and inotropes remain a cornerstone in stabilization of the severely impaired hemodynamics and cardiac output in cardiogenic shock (CS). The aim of this study was to analyze current real-life use of these medications, and their impact on outcome and on changes in cardiac and renal biomarkers over time in CS. The multinational CardShock study prospectively enrolled 219 patients with CS. The use of vasopressors and inotropes was analyzed in relation to the primary outcome, i.e., 90-day mortality, with propensity score methods in 216 patients with follow-up data available. Changes in cardiac and renal biomarkers over time until 96 hours from baseline were analyzed with linear mixed modeling. Patients were 67 (SD 12) years old, 26 % were women, and 28 % had been resuscitated from cardiac arrest prior to inclusion. On average, systolic blood pressure was 78 (14) and mean arterial pressure 57 (11) mmHg at detection of shock. 90-day mortality was 41 %. Vasopressors and/or inotropes were administered to 94 % of patients and initiated principally within the first 24 hours. Noradrenaline and adrenaline were given to 75 % and 21 % of patients, and 30 % received several vasopressors. In multivariable logistic regression, only adrenaline (21 %) was independently associated with increased 90-day mortality (OR 5.2, 95 % CI 1.88, 14.7, p = 0.002). The result was independent of prior cardiac arrest (39 % of patients treated with adrenaline), and the association remained in propensity-score-adjusted analysis among vasopressor-treated patients (OR 3.0, 95 % CI 1.3, 7.2, p = 0.013); this was further confirmed by propensity-score-matched analysis. Adrenaline was also associated, independent of prior cardiac arrest, with marked worsening of cardiac and renal biomarkers during the first days. Dobutamine and levosimendan were the most commonly used inotropes (49 % and 24 %). There were no differences in mortality, whether noradrenaline was combined

  5. Combination Therapy for the Cardiovascular Effects of Perinatal Lead Exposure in Young and Adult Rats

    International Nuclear Information System (INIS)

    Gaspar, Andréia Fresneda; Cordellini, Sandra

    2014-01-01

    Combination therapy can play a significant role in the amelioration of several toxic effects of lead (Pb) and recovery from associated cardiovascular changes. To investigate the effects of combination therapy on the cardiovascular effects of perinatal lead exposure in young and adult rats Female Wistar rats received drinking water with or without 500 ppm of Pb during pregnancy and lactation. Twenty-two- and 70-day-old rat offspring who were or were not exposed to Pb in the perinatal period received meso-dimercaptosuccinic acid (DMSA), L-arginine, or enalapril and a combination of these compounds for 30 additional days. Noradrenaline response curves were plotted for intact and denuded aortas from 23-, 52-, 70-, and 100-day-old rats stratified by perinatal Pb exposure (exposed/unexposed) and treatment received (treated/untreated). Systolic blood pressure was evaluated and shown to be higher in the 23-, 52-, 70-, and 100-day age groups with Pb exposure than in the corresponding control age groups: 117.8 ± 3.9*, 135.2 ± 1.3*, 139.6 ± 1.6*, and 131.7 ± 2.8*, respectively and 107.1 ± 1.8, 118.8 ± 2.1, 126.1 ± 1.1, and 120.5 ± 2.2, respectively (p < 0.05). Increased reactivity to noradrenaline was observed in intact, but not denuded, aortas from 52-, 70-, and 100-day-old exposed rats, and the maximum responses (g of tension) in the respective Pb-exposed and control age groups were as follows: 3.43 ± 0.16*, 4.32 ± 0.18*, and 4.21 ± 0.23*, respectively and 2.38 ± 0.33, 3.37 ± 0.13, and 3.22 ± 0.21, respectively (p < 0.05). All treatments reversed the changes in vascular reactivity to noradrenaline in rats perinatally exposed to Pb. The combination therapy resulted in an earlier restoration of blood pressure in Pb-exposed rats compared with the monotherapies, except for enalapril therapy in young rats. These findings represent a new approach to the development of therapeutic protocols for the treatment of Pb-induced hypertension

  6. Estimation of systemic catecholamine levels, in the Edible frog, using a radioenzymatic assay

    International Nuclear Information System (INIS)

    Bourgeois, Philippe; Dupont, Willy; Vaillant, Rene

    1978-01-01

    We have developed a radio-enzymatic assay for systemic catecholamines in the Frog. Such are its specificity and sensibility that adrenaline and noradrenaline may be measured in 50 μl of plasma samples, the withdrawal of which strongly influenced the results. The smaller values were obtained in plasma withdrawn from canulated animals. In this case, adrenaline was the major catecholamine in the plasma: 190 +- 55 ng/100 ml versus 35 +- 18 ng/100 ml for noradreline [fr

  7. Double isotope method for the determination of catecholamines, serotonin, and other amines in the picomole range as their dansyl derivatives

    International Nuclear Information System (INIS)

    Recasens, M.; Zwiller, J.; Mack, G.; Zanetta, J.P.; Mandel, P.

    1977-01-01

    A method based on thin-layer chromatographic separation of radioactive products is described for the determination and the quantification of dopamine (DA), noradrenaline (NA), adrenaline (A), normetanephrine (NMN), and serotonin (5HT) in small samples of brain tissue. In this method the amines are converted to [ 14 C]dansyl derivatives by reaction with [ 14 C]dansyl chloride [ 14 C]Dans-Cl) and 3 H-labeled amines are used as internal standards to determine variations in yield

  8. Exercise performance, core temperature, and metabolism after prolonged restricted activity and retraining in dogs

    Science.gov (United States)

    Nazar, K.; Greenleaf, J. E.; Pohoska, E.; Turlejska, E.; Kaciuba-Uscilko, H.; Kozlowski, S.

    1992-01-01

    Physiological effects of restricted activity (RA) and subsequent retraining have been studied. Ten male mongrel dogs performed a submaximal exercise endurance test on a treadmill during kennel control, after 8 weeks of cage confinement and after eight weeks of retraining using the same treadmill protocol 1 h/d for 6 d/week. Data obtained show that RA reduces exercise endurance, the effectiveness of exercise thermoregulation, muscle glycogen stores, and the lipolytic response to exercise and to noradrenaline stimulation.

  9. Neuro-ergonomic Research for Online Assessment of Cognitive Workload

    Science.gov (United States)

    2011-10-01

    than a visual-only format, since the audio form is also being used to carry information to the learner and ease the load experienced. It is 5 desirable...e.g., Catecholamine, Adrenaline, and Noradrenaline). Physiological measures can best be used to visualise the detailed trend and pattern of load (i.e...to reduce the noise and make the signals suitable for processing and visualisation . The filters are designed in such a way not to change or distort

  10. Determination of the changes of the plasma catecholamine level by radioenzymatic method following noise-exposition

    International Nuclear Information System (INIS)

    Pinter, Cs.; Vincze, I.

    1982-01-01

    A new method was applied for the determination of plasma catecholamine levels: all the catecholamines were methylated in the presence of S-adenosyl-1-methyl 3 H-methyonine and the radioactivity of the components - separated with thin-layer chromatography - was measured by liquid scintillation. It is concluded that noise exposition for one hour per day significantly increases the plasma concentration of noradrenaline and dopamine whereas the adrenaline-level shows biphasic change: after a short increase it decreases. (L.E.)

  11. On the role played by direct protection of the haemopoietic system cells in radioprotective action of some biogenous amines on the animal organism

    International Nuclear Information System (INIS)

    Smirnova, I.B.; Dontsova, G.V.; Yanushevskaya, M.I.; Graevskij, E.Ya.

    1975-01-01

    It has been found in mice, by a method of splenic exocolonies, that: (1) serotonin, adrenaline and noradrenaline can protect both isolated bone marrow cells and cells in situ (2) a considerable contribution to a radioprotective action of the amines under study on the animal organism is made by their direct protective effect on cells, (3) with serotonin and adrenaline, ''cell'' protection in the organism is added by a radioprotective action of tissue hypoxia caused by these amines

  12. Effects of Hypocretin/Orexin and Major Transmitters of Arousal on Fast Spiking Neurons in Mouse Cortical Layer 6B.

    Science.gov (United States)

    Wenger Combremont, Anne-Laure; Bayer, Laurence; Dupré, Anouk; Mühlethaler, Michel; Serafin, Mauro

    2016-08-01

    Fast spiking (FS) GABAergic neurons are thought to be involved in the generation of high-frequency cortical rhythms during the waking state. We previously showed that cortical layer 6b (L6b) was a specific target for the wake-promoting transmitter, hypocretin/orexin (hcrt/orx). Here, we have investigated whether L6b FS cells were sensitive to hcrt/orx and other transmitters associated with cortical activation. Recordings were thus made from L6b FS cells in either wild-type mice or in transgenic mice in which GFP-positive GABAergic cells are parvalbumin positive. Whereas in a control condition hcrt/orx induced a strong increase in the frequency, but not amplitude, of spontaneous synaptic currents, in the presence of TTX, it had no effect at all on miniature synaptic currents. Hcrt/orx effect was thus presynaptic although not by an action on glutamatergic terminals but rather on neighboring cells. In contrast, noradrenaline and acetylcholine depolarized and excited these cells through a direct postsynaptic action. Neurotensin, which is colocalized in hcrt/orx neurons, also depolarized and excited these cells but the effect was indirect. Morphologically, these cells exhibited basket-like features. These results suggest that hcrt/orx, noradrenaline, acetylcholine, and neurotensin could contribute to high-frequency cortical activity through an action on L6b GABAergic FS cells. © The Author 2016. Published by Oxford University Press.

  13. Protein kinase A mediates adenosine A2a receptor modulation of neurotransmitter release via synapsin I phosphorylation in cultured cells from medulla oblongata.

    Science.gov (United States)

    Matsumoto, Joao Paulo Pontes; Almeida, Marina Gomes; Castilho-Martins, Emerson Augusto; Costa, Maisa Aparecida; Fior-Chadi, Debora Rejane

    2014-08-01

    Synaptic transmission is an essential process for neuron physiology. Such process is enabled in part due to modulation of neurotransmitter release. Adenosine is a synaptic modulator of neurotransmitter release in the Central Nervous System, including neurons of medulla oblongata, where several nuclei are involved with neurovegetative reflexes. Adenosine modulates different neurotransmitter systems in medulla oblongata, specially glutamate and noradrenaline in the nucleus tractussolitarii, which are involved in hypotensive responses. However, the intracellular mechanisms involved in this modulation remain unknown. The adenosine A2a receptor modulates neurotransmitter release by activating two cAMP protein effectors, the protein kinase A and the exchange protein activated by cAMP. Therefore, an in vitro approach (cultured cells) was carried out to evaluate modulation of neurotransmission by adenosine A2a receptor and the signaling intracellular pathway involved. Results show that the adenosine A2a receptor agonist, CGS 21680, increases neurotransmitter release, in particular, glutamate and noradrenaline and such response is mediated by protein kinase A activation, which in turn increased synapsin I phosphorylation. This suggests a mechanism of A2aR modulation of neurotransmitter release in cultured cells from medulla oblongata of Wistar rats and suggest that protein kinase A mediates this modulation of neurotransmitter release via synapsin I phosphorylation. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  14. Beta2-adrenergic activity modulates vascular tone regulation in lecithin:cholesterol acyltransferase knockout mice

    Science.gov (United States)

    Manzini, S.; Pinna, C.; Busnelli, M.; Cinquanta, P.; Rigamonti, E.; Ganzetti, G.S.; Dellera, F.; Sala, A.; Calabresi, L.; Franceschini, G.; Parolini, C.; Chiesa, G.

    2015-01-01

    Lecithin:cholesterol acyltransferase (LCAT) deficiency is associated with hypoalphalipoproteinemia, generally a predisposing factor for premature coronary heart disease. The evidence of accelerated atherosclerosis in LCAT-deficient subjects is however controversial. In this study, the effect of LCAT deficiency on vascular tone and endothelial function was investigated in LCAT knockout mice, which reproduce the human lipoprotein phenotype. Aortas from wild-type (Lcatwt) and LCAT knockout (LcatKO) mice exposed to noradrenaline showed reduced contractility in LcatKO mice (P < 0.005), whereas acetylcholine exposure showed a lower NO-dependent relaxation in LcatKO mice (P < 0.05). Quantitative PCR and Western blotting analyses suggested an adequate eNOS expression in LcatKO mouse aortas. Real-time PCR analysis indicated increased expression of β2-adrenergic receptors vs wild-type mice. Aorta stimulation with noradrenaline in the presence of propranolol, to abolish the β-mediated relaxation, showed the same contractile response in the two mouse lines. Furthermore, propranolol pretreatment of mouse aortas exposed to L-NAME prevented the difference in responses between Lcatwt and LcatKO mice. The results indicate that LCAT deficiency leads to increased β2-adrenergic relaxation and to a consequently decreased NO-mediated vasodilation that can be reversed to guarantee a correct vascular tone. The present study suggests that LCAT deficiency is not associated with an impaired vascular reactivity. PMID:26254103

  15. Beta2-adrenergic activity modulates vascular tone regulation in lecithin:cholesterol acyltransferase knockout mice.

    Science.gov (United States)

    Manzini, S; Pinna, C; Busnelli, M; Cinquanta, P; Rigamonti, E; Ganzetti, G S; Dellera, F; Sala, A; Calabresi, L; Franceschini, G; Parolini, C; Chiesa, G

    2015-11-01

    Lecithin:cholesterol acyltransferase (LCAT) deficiency is associated with hypoalphalipoproteinemia, generally a predisposing factor for premature coronary heart disease. The evidence of accelerated atherosclerosis in LCAT-deficient subjects is however controversial. In this study, the effect of LCAT deficiency on vascular tone and endothelial function was investigated in LCAT knockout mice, which reproduce the human lipoprotein phenotype. Aortas from wild-type (Lcat(wt)) and LCAT knockout (Lcat(KO)) mice exposed to noradrenaline showed reduced contractility in Lcat(KO) mice (P<0.005), whereas acetylcholine exposure showed a lower NO-dependent relaxation in Lcat(KO) mice (P<0.05). Quantitative PCR and Western blotting analyses suggested an adequate eNOS expression in Lcat(KO) mouse aortas. Real-time PCR analysis indicated increased expression of β2-adrenergic receptors vs wild-type mice. Aorta stimulation with noradrenaline in the presence of propranolol, to abolish the β-mediated relaxation, showed the same contractile response in the two mouse lines. Furthermore, propranolol pretreatment of mouse aortas exposed to L-NAME prevented the difference in responses between Lcat(wt) and Lcat(KO) mice. The results indicate that LCAT deficiency leads to increased β2-adrenergic relaxation and to a consequently decreased NO-mediated vasodilation that can be reversed to guarantee a correct vascular tone. The present study suggests that LCAT deficiency is not associated with an impaired vascular reactivity. Copyright © 2015. Published by Elsevier Inc.

  16. Endogenous salivary α-amylase does not interact with skin conductance response during fear extinction in posttraumatic stress disorder.

    Science.gov (United States)

    Zuj, Daniel V; Palmer, Matthew A; Malhi, Gin S; Bryant, Richard A; Felmingham, Kim L

    2018-04-01

    Posttraumatic Stress Disorder (PTSD) is associated with elevated noradrenergic signaling, which has an impact on emotional learning and memory. Fear extinction is thought to underlie the processes of exposure therapy, however the relationship between noradrenaline and extinction in PTSD is unclear. Participants with PTSD (n = 21), trauma-exposure without PTSD (TC; n = 36), and non-trauma-exposed controls (NTC; n = 27) completed a fear conditioning and extinction paradigm, and conditioned fear was indexed by skin conductance response (SCR). Salivary α-amylase (sAA) collected at baseline and immediately post-fear acquisition was used as an index of noradrenaline, and we examined whether sAA in response to fear acquisition was a moderator between fear extinction and PTSD symptoms. While there was a significant increase in sAA from baseline to post-fear acquisition, this was not modulated by group. Compared to TC and NTC, the PTSD group displayed a slower decline in SCRs during early extinction, which generalized across stimulus type, and was not moderated by sAA. These findings suggest that the relationship between fear extinction and PTSD symptoms does not change as a function of sAA levels; however previous research suggests other processes of fear learning may be associated with noradrenergic activity in PTSD. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  17. Antidepressant-Like Effect of Lipid Extract of Channa striatus in Chronic Unpredictable Mild Stress Model of Depression in Rats

    Directory of Open Access Journals (Sweden)

    Mohamed Saleem Abdul Shukkoor

    2016-01-01

    Full Text Available This study evaluated the antidepressant-like effect of lipid extract of C. striatus in chronic unpredictable mild stress (CUMS model of depression in male rats and its mechanism of action. The animals were subjected to CUMS for six weeks by using variety of stressors. At the end of CUMS protocol, animals were subjected to forced swimming test (FST and open field test followed by biochemical assay. The CUMS protocol produced depressive-like behavior in rats by decreasing the body weight, decreasing the sucrose preference, and increasing the duration of immobility in FST. The CUMS protocol increased plasma corticosterone and decreased hippocampal and prefrontal cortex levels of monoamines (serotonin, noradrenaline, and dopamine and brain-derived neurotrophic factor. Further, the CUMS protocol increased interleukin-6 (in hippocampus and prefrontal cortex and nuclear factor-kappa B (in prefrontal cortex but not in hippocampus. The lipid extract of C. striatus (125, 250, and 500 mg/kg significantly (p<0.05 reversed all the above parameters in rats subjected to CUMS, thus exhibiting antidepressant-like effect. The mechanism was found to be mediated through decrease in plasma corticosterone, increase in serotonin levels in prefrontal cortex, increase in dopamine and noradrenaline levels in hippocampus and prefrontal cortex, increase in BDNF in hippocampus and prefrontal cortex, and decrease in IL-6 and NF-κB in prefrontal cortex.

  18. Stress and Fatigue in Operators Under Radiofrequency Electromagnetic Radiation and Shift Work

    Directory of Open Access Journals (Sweden)

    Vangelova K.

    2014-12-01

    Full Text Available The aim was to study the effect of radiofrequency electromagnetic radiation (EMR on stress indices, health complaints and fatigue of operators working fast-rotating extended shifts. Working conditions, job content, job control, social support, health complaints and fatigue were followed in 220 operators, 110 exposed to EMR and 110 control operators, matched by age and sex. The EMR was measured and time-weighted average (TWA was calculated. The excretion rates of stress hormones cortisol, adrenaline and noradrenaline were followed during the extended shifts in 36 operators, working at different levels of exposure and 24-hour exposure was calculated. The exposed group pointed more problems with the working conditions, including EMR, noise, currents and risk of accidents, more health complaints and higher level of fatigue. The most common health complaints were mental and physical exhaustion after work, pains in the chest, musculoskeletal complaints, headache, and apathy. High level EMR exposure (TWAmean = 3.10 μW/cm2, TWAmax = 137.00 μW/cm2 significantly increased the 24-hour excretion of cortisol and noradrenaline, whereas the increase of adrenaline excretion did not reach significance, as well as hormone excretion rates under low level exposure (TWAmean = 1.89 μW/cm2, TWAmax = 5.24 μW/cm2. In conclusion, higher number of health complaints, higher stress hormone excretion rates and fatigue were found in operators under EMR.

  19. Characterization of the positive and negative inotropic effects of acetylcholine in the human myocardium

    OpenAIRE

    Du, Xiaoyi; Schoemaker, Regien; Bos, Egbert; Saxena, Pramod Ranjan

    1995-01-01

    textabstractIn the human isolated myocardium, acetylcholine (10−9 to 10−3 M) elicited a biphasic inotropic effect (a decrease in the lower and an increase in the higher concentration range) in atrial and a positive inotropic effect in ventricular trabeculae. However, under conditions of raised contractility achieved by exposure to noradrenaline (10−5 M), only negative inotropic effects were observed in both atria and ventricles. Atropine (10−6 M), but not propranolol (10−6 M), antagonized bot...

  20. Iatrogenic nocturnal eneuresis- an overlooked side effect of anti histamines?

    Directory of Open Access Journals (Sweden)

    D Italiano

    2015-01-01

    Full Text Available Nocturnal enuresis is a common disorder in childhood, but its pathophysiological mechanisms have not been fully elucidated. Iatrogenic nocturnal enuresis has been described following treatment with several psychotropic medications. Herein, we describe a 6-year-old child who experienced nocturnal enuresis during treatment with the antihistamine cetirizine. Drug rechallenge was positive. Several neurotransmitters are implicated in the pathogenesis of nocturnal enuresis, including noradrenaline, serotonin and dopamine. Antihistamine treatment may provoke functional imbalance of these pathways resulting in incontinence.

  1. Night-rest urinary catecholamine excretion in relation to aspects of free time, work and background data in a teacher group.

    Science.gov (United States)

    Kinnunen, U; Vihko, V

    1991-01-01

    Free time, work and background data were related to night-rest catecholamine excretion rates in a teacher group (n = 137) during an autumn term. The explained interindividual variance increased slightly towards the end of the term. Adrenaline excretion was predicted better than noradrenaline, notedly by coffee consumption, amount of physical activity, and subjective stress feelings which explained 16% of the variance in adrenaline excretion during night rest. However, the results indicated that the differences in catecholamine excretion during night rest remained mostly unpredictable.

  2. Trauma Induced Coagulopathy

    DEFF Research Database (Denmark)

    Genét, Gustav Folmer; Johansson, Per; Meyer, Martin Abild Stengaard

    2013-01-01

    It remains debated whether traumatic brain injury (TBI) induces a different coagulopathy compared to non-TBI. This study investigated traditional coagulation tests, biomarkers of coagulopathy and endothelial damage in trauma patients with and without TBI. Blood from 80 adult trauma patients were...... sampled (median of 68 min (IQR 48-88) post-injury) upon admission to our trauma centre. Plasma/serum were retrospectively analysed for biomarkers reflecting sympathoadrenal activation (adrenaline, noradrenaline), coagulation activation/inhibition and fibrinolysis (protein C, activated protein C, tissue...

  3. Effect of head x-irradiation on adrenal medullary secretion

    International Nuclear Information System (INIS)

    Mieno, Masahiro

    1977-01-01

    The purpose of the present experiments was to investigate an immediate effect of head x-irradiation on the secretion of adrenaline and noradrenaline by the adrenal medulla. When the dogs were irradiated with 200 or 800 R of x-rays to their heads under pentobarbital anesthesia, the majority of the animals showed no stimulation of the adrenal medulla but the minority showed a slight but definite increase in the secretion of adrenaline, the peak being attained within 60 min after exposure. (auth.)

  4. Investigation of the mechanism of radioprotective action of adrenoceptor agonists

    International Nuclear Information System (INIS)

    Kulinskij, V.I.; Klimova, A.D.; Yashunskij, V.G.; Alpatova, T.V.; 4205700SU)

    1986-01-01

    α-Adrenoceptor agonists of both main groups, i.e. arylalkylamines and imidazolines, have a pronounced radioprotective effect. Their chemical analogs, which fail to stimulate α-adrenoceptors, do not protect mice. The effect of phenylephrine, adrenaline, and noradrenaline comes into play via α 1 -adrenoceptors and that of clonidine, via α 2 -adrenoceptors and also via α 1 -adrenoceptors. Adrenoceptor agonists can probably manifest their radioprotective action via both subtypes of α-adrenoceptors. Possible intracellular mechanisms of the radioprotective action are discussed

  5. Investigation of ionizing sublethal doses effects on endogenous radioresistance background

    International Nuclear Information System (INIS)

    Kudryashov, Yu.B.; Goncharenko, E.N.; Antonova, S.V.; Akhalaya, M.Ya.; Bajzhumanov, A.A.; Shestakova, S.V.

    1997-01-01

    Sublethal doses of X-radiation (0.5 Gy and 1 Gy) caused the alterations in levels of main components of endogenous radioresistance background in rat tissues. There were demonstrated the decrease of serotonin content in stomach mocosa and spleen, adrenalin, noradrenalin and corticosteroids contents in adrenal glands, nonprotein thiols content in spleen and the increase of lipid peroxide level in serum on the 3-14 days after irradiation. The recovery of the investigated parameters was occurred to the 21 day after exposure. (author)

  6. Pheochromocytoma with Negative Metanephrines: A Rarity and the Significance of Dopamine Secreting Tumors

    Directory of Open Access Journals (Sweden)

    Michael Bozin

    2017-05-01

    Full Text Available We describe a case of a 25-year-old female with a dopamine secreting PPGL diagnosed retrospectively with biochemical analysis. This finding resulted in change in approach to investigation and management, given their important clinical implications. There are important differences in management of dopamine secreting PPGL compared to classical noradrenaline and adrenaline-secreting PPGL. This includes the risk of peri-operative cardiovascular collapse peri-operatively with alpha/beta blockade, risk of malignancy/recurrence, and associated genetic abnormalities.

  7. Dopamine/noradrenaline reuptake inhibition in women improves endurance exercise performance in the heat.

    Science.gov (United States)

    Cordery, P; Peirce, N; Maughan, R J; Watson, P

    2017-11-01

    Catecholamine reuptake inhibition improves the performance of male volunteers exercising in warm conditions, but sex differences in thermoregulation, circulating hormones, and central neurotransmission may alter this response. With local ethics committee approval, nine physically active women (mean ± SD age 21 ± 2 years; height 1.68 ± 0.08 m; body mass 64.1 ± 6.0 kg; VO 2peak 51 ± 7 mL/kg/min) were recruited to examine the effect of pre-exercise administration of Bupropion (BUP; 4 × 150 mg) on prolonged exercise performance in a warm environment. Participants completed a VO 2peak test, two familiarization trials, and two randomized, double-blind experimental trials. All trials took place during the first 10 days of the follicular phase of the menstrual cycle. Participants cycled for 1 h at 60% VO 2peak followed by a 30-min performance test. Total work done was greater during the BUP trial (291 ± 48 kJ) than the placebo trial (269 ± 46 kJ, P = 0.042, d = 0.497). At the end of the performance test, core temperature was higher on the BUP trial (39.5 ± 0.4 °C) than on the placebo trial (39.2 ± 0.6 °C, P = 0.021; d = 0.588), as was heart rate (185 ± 9 vs 179 ± 13, P = 0.043; d = 0.537). The results indicate that during the follicular phase of the menstrual cycle, an acute dosing protocol of BUP can improve self-regulated performance in warm conditions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. On the action of radioprotective agents on the endogenous serotonin content and radiosensitivity of isolated Ehrlich ascites tumour and E. coli B. cells

    International Nuclear Information System (INIS)

    Goncharenko, E.N.; Gorskaya, T.G.; Gusareva, Eh.V.; Konstantinova, M.M.; Panyushkina, N.V.; AN SSSR, Moscow. Inst. Biologii Razvitiya)

    1976-01-01

    At a higher radioresistance level attained by incubation of isolated Ehrlich ascites tumour and E. coli B. cells with MEA or noradrenaline, the endogenous serotonin content of these cells was found to increase. The extent of radioresistance increase and the serotonin content of the cells were interrelated, i.e. washing the protector off cells decreased both the radioresistance and the content of endogenous serotonin. It is concluded that radioresistance of cells is connected with the content of biologically active substances (serotonin) that possess radioprotective action

  9. United States Air Force Research Initiation Program. 1984 Research Reports. Volume 2.

    Science.gov (United States)

    1986-05-01

    differential determination of adrenaline and noradrenaline in plasma." Clinica Chemica Acta. Vol. 30, pp. 373-376, 1970. 37. Stegemann, J., U. Meier, W...34%" . 1. Agh-anian, G. K. and R. Y. Wang. Physiology and Pharma - coloay cf central serotonergic neurons. In: Psych ph cl . j aGe tion A of P M...34, AIAA Journal, Vol. 18, No. 1, January 1980,"[ ’ "<. .’ip p . 1 1 - 1 5 . 39. Rotta, J.C., "Temperaturverteilungen in der Turbulenten Grenzschicht an

  10. Effect of β-endorphin on catecholamine levels in rat hypothalamus and cerebral cortex

    International Nuclear Information System (INIS)

    Slavnov, V.N.; Valueva, G.V.; Markov, V.V.; Luchitskii, E.V.

    1986-01-01

    The authors studied the effect of beta-endorphin on catecholamine concentrations in the hypothalmus and cerebral cortex in rats, as a contribution to the explanation of the mechanism of action of this peptide on certain pituitary trophic functions. Concentrations of dopamine, noradrenalin, and adrenalin were determined by a radioenzymatic method. A Mark 3 scintillation system was used for radiometric investigation of the samples. The results of these experiments indicate that beta-endorphin has a marked effect on brain catecholamine levels mainly in the hypothalamus

  11. Carotid body paraganglioma metastatic to bone: report of two cases

    International Nuclear Information System (INIS)

    Kawai, A.; Healey, J.H.; Wilson, S.C.; Huvos, A.G.; Yeh, S.D.J.

    1998-01-01

    Two patients with carotid body paraganglioma developed bone metastases 3 and 6 years respectively after surgical excision of the primary tumors. Plain radiographs showed ill-defined metastatic lesions. Scintigram using radiolabeled metaiodobenzylguanidine, an analogue of noradrenaline that is taken up by neurosecretary granules, showed an abnormal accumulation in the corresponding metastatic lesion. Histologically, nests of epithelioid cells with clear cytoplasm and pyknotic nuclei and abundant collagen fibers were observed within destroyed trabeculae. Treatment including external radiation and surgery provided pain relief and early local disease control. (orig.)

  12. Effect of. beta. -endorphin on catecholamine levels in rat hypothalamus and cerebral cortex

    Energy Technology Data Exchange (ETDEWEB)

    Slavnov, V.N.; Valueva, G.V.; Markov, V.V.; Luchitskii, E.V.

    1986-10-01

    The authors studied the effect of beta-endorphin on catecholamine concentrations in the hypothalmus and cerebral cortex in rats, as a contribution to the explanation of the mechanism of action of this peptide on certain pituitary trophic functions. Concentrations of dopamine, noradrenalin, and adrenalin were determined by a radioenzymatic method. A Mark 3 scintillation system was used for radiometric investigation of the samples. The results of these experiments indicate that beta-endorphin has a marked effect on brain catecholamine levels mainly in the hypothalamus.

  13. Catecholamines of the body tissues and radiosensitivity of rodents

    International Nuclear Information System (INIS)

    Grayevskaya, V.M.; Zolotariova, N.N.

    1975-01-01

    Various species of rodents are distinguished by their radiosensitivity (increasing): bank vole 57 Br mouse < golden hamster < BALB mouse < guinea pig. There is a positive correlation between radiosensitivity of these species and catecholamines content in the adrenals, urea and blood; and negative correlation between radiosensitivity and adrenaline and noradrenaline concentrations in liver and spleen cells. Presumable causes of this correlation, and the possibility of application of the index under study for predicting the organism radiosensitivity and forecasting the outcome of radiation damage are discussed

  14. Neuroendocrine responses to hypoglycaemia decrease within the first year after diagnosis of type 1 diabetes

    DEFF Research Database (Denmark)

    Damholt, M B; Christensen, N J; Hilsted, Jannik

    2001-01-01

    in neuroendocrine responses occur early in the course of diabetes, we investigated the responses to insulin-induced hxypoglycaemia during the first year of type 1 diabetes. Autonomic and somatic nerve function tests were performed concomitantly. Six type 1 diabetes patients were studied 3 and 12 months after.......025) and noradrenaline (p 12 months compared with 3 months after diagnosis of type 1 diabetes. Rate of glucose recovery did not differ at month 12 compared with month 3. Cardiovascular autonomic nerve function tests did not change and remained...

  15. Evidence for a functional vasoconstrictor role for ATP in the human cutaneous microvasculature.

    Science.gov (United States)

    Lang, James A; Krajek, Alex C; Smaller, Kevin A

    2017-06-01

    What is the central question of this study? In young adults, about half of the cold-related reduction in skin blood flow during cold exposure is mediated by noradrenaline, while the remainder is attributable to other substances co-released with noradrenaline that have yet to be identified. What is the main finding and its importance? Purinergic receptor blockade blunted the vasoconstriction response to whole-body cooling and to intradermal administration of tyramine. These results indicate that ATP is necessary to vasoconstrict blood vessels in the skin adequately and prevent heat loss in a cold environment. Noradrenaline is responsible for eliciting ∼60% of the reflex cutaneous vasoconstriction (VC) response in young adults, while the remainder is attributable to one or more unidentified co-released sympathetic adrenergic neurotransmitter(s). Inconsistent evidence has placed neuropeptide Y in this role; however, other putative cotransmitters have yet to be tested. We hypothesize that ATP contributes to the reflex cutaneous VC response. Two protocols were conducted in young adults (n = 10); both involved the placement of three microdialysis probes in forearm skin and whole-body cooling (skin temperature = 30.5°C). In protocol 1, the following solutions were infused: (i) lactated Ringer solution (control); (ii) 10 mm l-NAME; and (iii) purinergic receptor blockade with 1 mm suramin plus l-NAME. In protocol 2, the following solutions were infused: (i) lactated Ringer solution; (ii) suramin plus l-NAME; and (iii) suramin plus l-NAME plus adrenoreceptor blockade with 5 mm yohimbine plus 1 mm propranolol. Laser Doppler flux (LDF) was measured over each microdialysis site, and cutaneous vascular conductance (CVC) was calculated (CVC = LDF/MAP) and expressed as percentage changes from baseline (%ΔCVC BASELINE ). l-NAME was used to block the vasodilatory influence of ATP and unmask the P 2 X-mediated VC response to exogenous ATP infusion (-21 ± 6%

  16. Case Study of Hepatic Radiofrequency Ablation Causing a Systemic Inflammatory Response Under Total Intravenous Anesthesia

    Energy Technology Data Exchange (ETDEWEB)

    Schalte, Gereon; Waning, Christian; Rossaint, Rolf; Mahnken, Andreas H. [University Hospital, RWTH Aachen, Aachen, (Germany); Henzler, Dietrich [Dalhousie University, Queen Elisabeth II Health Sciences Center, Halifax (Canada); Tacke, Josef [Interventional Radiology, Klinikum Passau, Passau (Germany)

    2010-12-15

    To investigate the effects of hepatic radiofrequency ablation (RFA) in patients with malignant liver disease with respect to inflammation activation and stress response. In an observational trial, we investigated the physiologic parameters of 17 patients (20 interventions) who underwent percutaneous RFA under general anesthesia after applying total intravenous anesthesia. TNF{alpha}, IL-6, IL-8, IL-10, adrenaline and noradrenaline, liver enzymes, lactate and creatine kinase were determined pre-interventionally after induction of anesthesia (T1), 90 minutes after initiation of RFA (T2), immediately after the conclusion of the procedure (T3), and 24 hours after the procedure (T4). A significant increase in body temperature (p < 0.001), and mean arterial pressure (p = 0.001) were measured intraoperatively (T2) and the day after the procedure (T4). Increased levels of IL-6 were measured at T3 and T4 (p = 0.001). IL-10 increased immediately after the procedure (T3; p = 0.007). IL-6 levels correlated well with the total energy applied ({gamma} = 0.837). Significant increases in the levels of adrenaline and noradrenaline were present at T3 and T4 (p < 0.001). The RFA-induced destruction of hepatic tissue was associated with increased levels of AST, ALT, GLDH and LDH. Percutaneous RFA of hepatic malignancies causes an inflammatory and endocrine activation, similar to the systemic inflammatory response syndrome. These effects have to be taken in account when dealing with patients susceptible to sepsis or multi-organ failure

  17. Direct and indirect cardiovascular actions of cathinone and MDMA in the anaesthetized rat.

    Science.gov (United States)

    Alsufyani, Hadeel A; Docherty, James R

    2015-07-05

    The stimulants cathinone (from Khat leaves) and methylenedioxymeth-amphetamine (MDMA) produce adrenoceptor mediated tachycardia and vasopressor actions that may be the result of direct receptor stimulation, actions on the noradrenaline transporter, and/or displacement of noradrenaline from nerve terminals. Effects of cathinone or MDMA were compared with those of the indirect sympathomimetic tyramine. Male Wistar rats were anaesthetized with pentobarbitone for blood pressure and heart rate recording. Some rats were sympathectomised by treatment with 6-hydroxydopamine. In the anaesthetised rat, cathinone, MDMA and tyramine (all 0.001-1 mg/kg) produced marked tachycardia, tyramine produced marked pressor responses and MDMA produced small pressor responses. The tachycardia to cathinone and MDMA was almost abolished by propranolol (1mg/kg). Pretreatment with cocaine (1mg/kg) did not significantly affect the tachycardia to cathinone or MDMA, but reduced the response to tyramine. However, in sympathectomised rats, the tachycardia to cathinone or MDMA was markedly attenuated, but the tachycardia to tyramine was only partially reduced. Blood pressure effects of tyramine and MDMA were also markedly attenuated by sympathectomy. The results demonstrate firstly that cocaine may not be the most suitable agent for assessing direct versus indirect agonism in cardiovascular studies. Secondly, the use of chemical sympathectomy achieved the desired goal of demonstrating that cardiac β-adrenoceptor mediated actions of cathinone and MDMA are probably largely indirect. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Combined treatment with atorvastatin and imipenem improves survival and vascular functions in mouse model of sepsis.

    Science.gov (United States)

    Choudhury, Soumen; Kannan, Kandasamy; Pule Addison, M; Darzi, Sazad A; Singh, Vishakha; Singh, Thakur Uttam; Thangamalai, Ramasamy; Dash, Jeevan Ranjan; Parida, Subhashree; Debroy, Biplab; Paul, Avishek; Mishra, Santosh Kumar

    2015-08-01

    We have recently reported that pre-treatment, but not the post-treatment with atorvastatin showed survival benefit and improved hemodynamic functions in cecal ligation and puncture (CLP) model of sepsis in mice. Here we examined whether combined treatment with atorvastatin and imipenem after onset of sepsis can prolong survival and improve vascular functions. At 6 and 18h after sepsis induction, treatment with atorvastatin plus imipenem, atorvastatin or imipenem alone or placebo was initiated. Ex vivo experiments were done on mouse aorta to examine the vascular reactivity to nor-adrenaline and acetylcholine and mRNA expressions of α1D AR, GRK2 and eNOS. Atorvastatin plus imipenem extended the survival time to 56.00±4.62h from 20.00±1.66h observed in CLP mice. The survival time with atorvastatin or imipenem alone was 20.50±1.89h and 27.00±4.09h, respectively. The combined treatment reversed the hyporeactivity to nor-adrenaline through preservation of α1D AR mRNA/protein expression and reversal of α1D AR desensitization mediated by GRK2/Gβγ pathway. The treatment also restored endothelium-dependent relaxation to ACh through restoration of aortic eNOS mRNA expression and NO availability. In conclusion, combined treatment with atorvastatin and imipenem exhibited survival benefit and improved vascular functions in septic mice. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Cold-induced vasoconstriction at forearm and hand skin sites: the effect of age.

    Science.gov (United States)

    Kingma, B R M; Frijns, A J H; Saris, W H M; van Steenhoven, A A; van Marken Lichtenbelt, W D

    2010-07-01

    During mild cold exposure, elderly are at risk of hypothermia. In humans, glabrous skin at the hands is well adapted as a heat exchanger. Evidence exists that elderly show equal vasoconstriction due to local cooling at the ventral forearm, yet no age effects on vasoconstriction at hand skin have been studied. Here, we tested the hypotheses that at hand sites (a) elderly show equal vasoconstriction due to local cooling and (b) elderly show reduced response to noradrenergic stimuli. Skin perfusion and mean arterial pressure were measured in 16 young adults (Y: 18-28 years) and 16 elderly (E: 68-78 years). To study the effect of local vasoconstriction mechanisms local sympathetic nerve terminals were blocked by bretylium (BR). Baseline local skin temperature was clamped at 33 degrees C. Next, local temperature was reduced to 24 degrees C. After 15 min of local cooling, noradrenaline (NA) was administered to study the effect of neural vasoconstriction mechanisms. No significant age effect was observed in vasoconstriction due to local cooling at BR sites. After NA, vasoconstriction at the forearm showed a significant age effect; however, no significant age effect was found at the hand sites. [Change in CVC (% from baseline): Forearm Y: -76 +/- 3 vs. E: -60 +/- 5 (P forearm, elderly did not show a blunted response to local cooling and noradrenaline at hand skin sites. This indicates that at hand skin the noradrenergic mechanism of vasoconstriction is maintained with age.

  20. Case Study of Hepatic Radiofrequency Ablation Causing a Systemic Inflammatory Response Under Total Intravenous Anesthesia

    International Nuclear Information System (INIS)

    Schalte, Gereon; Waning, Christian; Rossaint, Rolf; Mahnken, Andreas H.; Henzler, Dietrich; Tacke, Josef

    2010-01-01

    To investigate the effects of hepatic radiofrequency ablation (RFA) in patients with malignant liver disease with respect to inflammation activation and stress response. In an observational trial, we investigated the physiologic parameters of 17 patients (20 interventions) who underwent percutaneous RFA under general anesthesia after applying total intravenous anesthesia. TNFα, IL-6, IL-8, IL-10, adrenaline and noradrenaline, liver enzymes, lactate and creatine kinase were determined pre-interventionally after induction of anesthesia (T1), 90 minutes after initiation of RFA (T2), immediately after the conclusion of the procedure (T3), and 24 hours after the procedure (T4). A significant increase in body temperature (p < 0.001), and mean arterial pressure (p = 0.001) were measured intraoperatively (T2) and the day after the procedure (T4). Increased levels of IL-6 were measured at T3 and T4 (p = 0.001). IL-10 increased immediately after the procedure (T3; p = 0.007). IL-6 levels correlated well with the total energy applied (γ = 0.837). Significant increases in the levels of adrenaline and noradrenaline were present at T3 and T4 (p < 0.001). The RFA-induced destruction of hepatic tissue was associated with increased levels of AST, ALT, GLDH and LDH. Percutaneous RFA of hepatic malignancies causes an inflammatory and endocrine activation, similar to the systemic inflammatory response syndrome. These effects have to be taken in account when dealing with patients susceptible to sepsis or multi-organ failure

  1. Protein targeting to glycogen is a master regulator of glycogen synthesis in astrocytes

    KAUST Repository

    Ruchti, E.

    2016-10-08

    The storage and use of glycogen, the main energy reserve in the brain, is a metabolic feature of astrocytes. Glycogen synthesis is regulated by Protein Targeting to Glycogen (PTG), a member of specific glycogen-binding subunits of protein phosphatase-1 (PPP1). It positively regulates glycogen synthesis through de-phosphorylation of both glycogen synthase (activation) and glycogen phosphorylase (inactivation). In cultured astrocytes, PTG mRNA levels were previously shown to be enhanced by the neurotransmitter noradrenaline. To achieve further insight into the role of PTG in the regulation of astrocytic glycogen, its levels of expression were manipulated in primary cultures of mouse cortical astrocytes using adenovirus-mediated overexpression of tagged-PTG or siRNA to downregulate its expression. Infection of astrocytes with adenovirus led to a strong increase in PTG expression and was associated with massive glycogen accumulation (>100 fold), demonstrating that increased PTG expression is sufficient to induce glycogen synthesis and accumulation. In contrast, siRNA-mediated downregulation of PTG resulted in a 2-fold decrease in glycogen levels. Interestingly, PTG downregulation strongly impaired long-term astrocytic glycogen synthesis induced by insulin or noradrenaline. Finally, these effects of PTG downregulation on glycogen metabolism could also be observed in cultured astrocytes isolated from PTG-KO mice. Collectively, these observations point to a major role of PTG in the regulation of glycogen synthesis in astrocytes and indicate that conditions leading to changes in PTG expression will directly impact glycogen levels in this cell type.

  2. Effects of dietary amines on the gut and its vasculature.

    Science.gov (United States)

    Broadley, Kenneth J; Akhtar Anwar, M; Herbert, Amy A; Fehler, Martina; Jones, Elen M; Davies, Wyn E; Kidd, Emma J; Ford, William R

    2009-06-01

    Trace amines, including tyramine and beta-phenylethylamine (beta-PEA), are constituents of many foods including chocolate, cheeses and wines and are generated by so-called 'friendly' bacteria such as Lactobacillus, Lactococcus and Enterococcus species, which are found in probiotics. We therefore examined whether these dietary amines could exert pharmacological effects on the gut and its vasculature. In the present study we examined the effects of tyramine and beta-PEA on the contractile activity of guinea-pig and rat ileum and upon the isolated mesenteric vasculature and other blood vessels. Traditionally, these amines are regarded as sympathomimetic amines, exerting effects through the release of noradrenaline from sympathetic nerve endings, which should relax the gut. A secondary aim was therefore to confirm this mechanism of action. However, contractile effects were observed in the gut and these were independent of noradrenaline, acetylcholine, histamine and serotonin receptors. They were therefore probably due to the recently described trace amine-associated receptors. These amines relaxed the mesenteric vasculature. In contrast, the aorta and coronary arteries were constricted, a response that was also independent of a sympathomimetic action. From these results, we propose that after ingestion, trace amines could stimulate the gut and improve intestinal blood flow. Restriction of blood flow elsewhere diverts blood to the gut to aid digestion. Thus, trace amines in the diet may promote the digestive process through stimulation of the gut and improved gastrointestinal circulation.

  3. Adrenergic receptor-mediated modulation of striatal firing patterns.

    Science.gov (United States)

    Ohta, Hiroyuki; Kohno, Yu; Arake, Masashi; Tamura, Risa; Yukawa, Suguru; Sato, Yoshiaki; Morimoto, Yuji; Nishida, Yasuhiro; Yawo, Hiromu

    2016-11-01

    Although noradrenaline and adrenaline are some of the most important neurotransmitters in the central nervous system, the effects of noradrenergic/adrenergic modulation on the striatum have not been determined. In order to explore the effects of adrenergic receptor (AR) agonists on the striatal firing patterns, we used optogenetic methods which can induce continuous firings. We employed transgenic rats expressing channelrhodopsin-2 (ChR2) in neurons. The medium spiny neuron showed a slow rising depolarization during the 1-s long optogenetic striatal photostimulation and a residual potential with 8.6-s half-life decay after the photostimulation. As a result of the residual potential, five repetitive 1-sec long photostimulations with 20-s onset intervals cumulatively increased the number of spikes. This 'firing increment', possibly relating to the timing control function of the striatum, was used to evaluate the AR modulation. The β-AR agonist isoproterenol decreased the firing increment between the 1st and 5th stimulation cycles, while the α 1 -AR agonist phenylephrine enhanced the firing increment. Isoproterenol and adrenaline increased the early phase (0-0.5s of the photostimulation) firing response. This adrenergic modulation was inhibited by the β-antagonist propranolol. Conversely, phenylephrine and noradrenaline reduced the early phase response. β-ARs and α 1 -ARs work in opposition controlling the striatal firing initiation and the firing increment. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  4. Effects of methylphenidate on attention in Wistar rats treated with the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4).

    Science.gov (United States)

    Hauser, Joachim; Reissmann, Andreas; Sontag, Thomas-A; Tucha, Oliver; Lange, Klaus W

    2017-05-01

    The aim of this study was to assess the effects of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on attention in rats as measured using the 5-choice-serial-reaction-time task (5CSRTT) and to investigate whether methylphenidate has effects on DSP4-treated rats. Methylphenidate is a noradrenaline and dopamine reuptake inhibitor and commonly used in the pharmacological treatment of individuals with attention deficit/hyperactivity disorder (ADHD). Wistar rats were trained in the 5CSRTT and treated with one of three doses of DSP4 or saline. Following the DSP4 treatment rats were injected with three doses of methylphenidate or saline and again tested in the 5CSRTT. The treatment with DSP4 caused a significant decline of performance in the number of correct responses and a decrease in response accuracy. A reduction in activity could also be observed. Whether or not the cognitive impairments are due to attention deficits or changes in explorative behaviour or activity remains to be investigated. The treatment with methylphenidate had no beneficial effect on the rats' performance regardless of the DSP4 treatment. In the group without DSP4 treatment, methylphenidate led to a reduction in response accuracy and bidirectional effects in regard to parameters related to attention. These findings support the role of noradrenaline in modulating attention and call for further investigations concerning the effects of methylphenidate on attentional processes in rats.

  5. Amphetamine and cocaine suppress social play behavior in rats through distinct mechanisms.

    Science.gov (United States)

    Achterberg, E J Marijke; Trezza, Viviana; Siviy, Stephen M; Schrama, Laurens; Schoffelmeer, Anton N M; Vanderschuren, Louk J M J

    2014-04-01

    Social play behavior is a characteristic form of social behavior displayed by juvenile and adolescent mammals. This social play behavior is highly rewarding and of major importance for social and cognitive development. Social play is known to be modulated by neurotransmitter systems involved in reward and motivation. Interestingly, psychostimulant drugs, such as amphetamine and cocaine, profoundly suppress social play, but the neural mechanisms underlying these effects remain to be elucidated. In this study, we investigated the pharmacological underpinnings of amphetamine- and cocaine-induced suppression of social play behavior in rats. The play-suppressant effects of amphetamine were antagonized by the alpha-2 adrenoreceptor antagonist RX821002 but not by the dopamine receptor antagonist alpha-flupenthixol. Remarkably, the effects of cocaine on social play were not antagonized by alpha-2 noradrenergic, dopaminergic, or serotonergic receptor antagonists, administered either alone or in combination. The effects of a subeffective dose of cocaine were enhanced by a combination of subeffective doses of the serotonin reuptake inhibitor fluoxetine, the dopamine reuptake inhibitor GBR12909, and the noradrenaline reuptake inhibitor atomoxetine. Amphetamine, like methylphenidate, exerts its play-suppressant effect through alpha-2 noradrenergic receptors. On the other hand, cocaine reduces social play by simultaneous increases in dopamine, noradrenaline, and serotonin neurotransmission. In conclusion, psychostimulant drugs with different pharmacological profiles suppress social play behavior through distinct mechanisms. These data contribute to our understanding of the neural mechanisms of social behavior during an important developmental period, and of the deleterious effects of psychostimulant exposure thereon.

  6. Treatment of anxiety and depression: medicinal plants in retrospect.

    Science.gov (United States)

    Fajemiroye, James O; da Silva, Dayane M; de Oliveira, Danillo R; Costa, Elson A

    2016-06-01

    Anxiety and depression are complex heterogeneous psychiatric disorders and leading causes of disability worldwide. This review summarizes reports on the fundamentals, prevalence, diagnosis, neurobiology, advancement in treatment of these diseases and preclinical assessment of botanicals. This review was conducted through bibliographic investigation of scientific journals, books, electronic sources, unpublished theses and electronic medium such as ScienceDirect and PubMed. A number of the first-line drugs (benzodiazepine, azapirone, antidepressant tricyclics, monoamine oxidase inhibitors, serotonin selective reuptake inhibitors, noradrenaline reuptake inhibitors, serotonin and noradrenaline reuptake inhibitors, etc.) for the treatment of these psychiatric disorders are products of serendipitous discoveries. Inspite of the numerous classes of drugs that are available for the treatment of anxiety and depression, full remission has remained elusive. The emerging clinical cases have shown increasing interests among health practitioners and patients in phytomedicine. The development of anxiolytic and antidepressant drugs of plant origin takes advantage of multidisciplinary approach including but not limited to ethnopharmacological survey (careful investigation of folkloric application of medicinal plant), phytochemical and pharmacological studies. The selection of a suitable plant for a pharmacological study is a basic and very important step. Relevant clues to achieving this step include traditional use, chemical composition, toxicity, randomized selection or a combination of several criteria. Medicinal plants have been and continue to be a rich source of biomolecule with therapeutic values for the treatment of anxiety and depression. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  7. Pharmacological manipulations in animal models of anorexia and binge eating in relation to humans.

    Science.gov (United States)

    van Gestel, M A; Kostrzewa, E; Adan, R A H; Janhunen, S K

    2014-10-01

    Eating disorders, such as anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorders (BED), are described as abnormal eating habits that usually involve insufficient or excessive food intake. Animal models have been developed that provide insight into certain aspects of eating disorders. Several drugs have been found efficacious in these animal models and some of them have eventually proven useful in the treatment of eating disorders. This review will cover the role of monoaminergic neurotransmitters in eating disorders and their pharmacological manipulations in animal models and humans. Dopamine, 5-HT (serotonin) and noradrenaline in hypothalamic and striatal regions regulate food intake by affecting hunger and satiety and by affecting rewarding and motivational aspects of feeding. Reduced neurotransmission by dopamine, 5-HT and noradrenaline and compensatory changes, at least in dopamine D2 and 5-HT(2C/2A) receptors, have been related to the pathophysiology of AN in humans and animal models. Also, in disorders and animal models of BN and BED, monoaminergic neurotransmission is down-regulated but receptor level changes are different from those seen in AN. A hypofunctional dopamine system or overactive α2-adrenoceptors may contribute to an attenuated response to (palatable) food and result in hedonic binge eating. Evidence for the efficacy of monoaminergic treatments for AN is limited, while more support exists for the treatment of BN or BED with monoaminergic drugs. © 2014 The British Pharmacological Society.

  8. Neuron-glia metabolic coupling: Role in plasticity and neuroprotection

    KAUST Repository

    Magistretti, Pierre J.

    2017-12-02

    A tight metabolic coupling between astrocytes and neurons is a key feature of brain energy metabolism (Magistretti and Allaman, Neuron, 2015). Over the years we have described two basic mechanisms of neurometabolic coupling. First the glycogenolytic effect of VIP and of noradrenaline indicating a regulation of brain homeostasis by neurotransmitters acting on astrocytes, as glycogen is exclusively localized in these cells. Second, the glutamate-stimulated aerobic glycolysis in astrocytes. Both the VIP-and noradrenaline-induced glycogenolysis and the glutamate-stimulated aerobic glycolysis result in the release of lactate from astrocytes as an energy substrate for neurons (Magistretti and Allaman, Neuron, 2015). We have recently shown that lactate is necessary not only as an energy substrate but is also a signaling molecule for long-term memory consolidation and for maintenance of LTP (Suzuki et al, Cell, 2011). At the molecular level we have found that L-lactate stimulates the expression of synaptic plasticity-related genes such as Arc, Zif268 and BDNF through a mechanism involving NMDA receptor activity and its downstream signaling cascade Erk1/2 (Yang et al, PNAS, 2014). L-lactate potentiates NMDA receptor-mediated currents and the ensuing increases in intracellular calcium. These results reveal a novel action of L-lactate as a signaling molecule for neuronal plasticity. We have also recently shown that peripheral administration of lactate exerts antidepressant-like effects in three animal models of depression (Carrard et al, Mol.Psy., 2016).

  9. Protective role of AgRP neuron's PDK1 against salt-induced hypertension.

    Science.gov (United States)

    Zhang, Boyang; Nakata, Masanori; Lu, Ming; Nakae, Jun; Okada, Takashi; Ogawa, Wataru; Yada, Toshihiko

    2018-06-12

    In the hypothalamic arcuate nucleus (ARC), orexigenic agouti-related peptide (AgRP) neurons regulate feeding behavior and energy homeostasis. The 3-phosphoinositide-dependent protein kinase-1 (PDK1) in AgRP neurons serves as a major signaling molecule for leptin and insulin, the hormones regulating feeding behavior, energy homeostasis and circulation. However, it is unclear whether PDK1 in AGRP neurons is also involved in regulation of blood pressure. This study explored it by generating and analyzing AgRP neuron-specific PDK1 knockout (Agrp-Pdk1 flox/flox ) mice and effect of high salt diet on blood pressure in KO and WT mice was analyzed. Under high salt diet feeding, systolic blood pressure (SBP) of Agrp-Pdk1 flox/flox mice was significantly elevated compared to Agrp-Cre mice. When the high salt diet was switched to control low salt diet, SBP of Agrp-Pdk1 flox/flox mice returned to the basal level observed in Agrp-Cre mice within 1 week. In Agrp-Pdk1 flox/flox mice, urinary noradrenalin excretion and NUCB2 mRNA expression in hypothalamic paraventricular nucleus (PVN) were markedly upregulated. Moreover, silencing of NUCB2 in the PVN counteracted the rises in urinary noradrenalin excretions and SBP. These results demonstrate a novel role of PDK1 in AgRP neurons to counteract the high salt diet-induced hypertension by preventing hyperactivation of PVN nesfatin-1 neurons. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Tryptophan depletion affects compulsive behaviour in rats

    DEFF Research Database (Denmark)

    Merchán, A; Navarro, S V; Klein, A B

    2017-01-01

    investigated whether 5-HT manipulation, through a tryptophan (TRP) depletion by diet in Wistar and Lister Hooded rats, modulates compulsive drinking in schedule-induced polydipsia (SIP) and locomotor activity in the open-field test. The levels of dopamine, noradrenaline, serotonin and its metabolite were......-depleted HD Wistar rats, while the LD Wistar and the Lister Hooded rats did not exhibit differences in SIP. In contrast, the TRP-depleted Lister Hooded rats increased locomotor activity compared to the non-depleted rats, while no differences were found in the Wistar rats. Serotonin 2A receptor binding...

  11. The effect of altitude hypoxia on glucose homeostasis in men

    DEFF Research Database (Denmark)

    Larsen, J J; Hansen, J M; Olsen, Niels Vidiendal

    1997-01-01

    1. Exposure to altitude hypoxia elicits changes in glucose homeostasis with increases in glucose and insulin concentrations within the first few days at altitude. Both increased and unchanged hepatic glucose production (HGP) have previously been reported in response to acute altitude hypoxia...... (noradrenaline and adrenaline) and day 7 (adrenaline), but not at sea level. 4. In conclusion, insulin action decreases markedly in response to two days of altitude hypoxia, but improves with more prolonged exposure. HGP is always unchanged. The changes in insulin action may in part be explained by the changes...

  12. Elevations in core and muscle temperature impairs repeated sprint performance

    DEFF Research Database (Denmark)

    Drust, B.; Rasmussen, P.; Mohr, Magni

    2005-01-01

    on a cycle ergometer in normal (approximately 20 degrees C, control) and hot (40 degrees C, hyperthermia) environments. RESULTS: Completion of the intermittent protocol in the heat elevated core and muscle temperatures (39.5 +/- 0.2 degrees C; 40.2 +/- 0.4 degrees C), heart rate (178 +/- 11 beats min(-1...... metabolic fatigue agents and we, therefore, suggest that it may relate to the influence of high core temperature on the function of the central nervous system.......)), rating of perceived exertion (RPE) (18 +/- 1) and noradrenaline (38.9 +/- 13.2 micromol l(-1)) (all P

  13. Transient thyrotoxicosis from thyroiditis induced by sibutramine overdose: a case report.

    Science.gov (United States)

    Kim, S K; Lee, S M; Yoo, S S; Hahm, J R; Jung, J H; Kim, H S; Kim, S; Chung, S I; Jung, T S

    2013-08-01

    Sibutramine is an antiobesity drug that inhibits the reuptake of serotonin and noradrenalin in the hypothalamus. A 37-year-old Korean man presented to the emergency room for the oral intake of 280 mg of sibutramine. The patient was in thyrotoxic state. The (99m)Technetium-pertechnetate thyroid scan showed irregular uptake of radioisotope and thyroid-stimulating hormone receptor antibody and thyroperoxidase antibody were negative. Thyroid function normalized after that. The patient had transient thyrotoxicosis with thyroiditis. We report a case of thyrotoxicosis accompanied by thyroiditis resulting from the intentional overdose of sibutramine.

  14. Dopamine hypothesis of mania

    OpenAIRE

    Cookson, John

    2014-01-01

    s­of­the­Speakers­/­Konuşmacı­leriThe discovery of dopamine and its pathwaysDopamine (DA) was first synthesized in 1910 from 3,4-dihydroxy phenyl alanine (DOPA) by Barger and Ewens at Wellcome Laboratories in London. It is a cathecholamine and in the 1940s Blaschko in Cambridge proposed that DA was a precursor in synthesis of the cat-echolamine neurotransmitters noradrenaline (norepinephrine) and adrenaline (epinephrine). In 1957 it was shown to be present in the brain with other catecholamin...

  15. Deep brain stimulation reveals emotional impact processing in ventromedial prefrontal cortex

    DEFF Research Database (Denmark)

    Gjedde, Albert; Geday, Jacob

    2009-01-01

    We tested the hypothesis that modulation of monoaminergic tone with deep-brain stimulation (DBS) of subthalamic nucleus would reveal a site of reactivity in the ventromedial prefrontal cortex that we previously identified by modulating serotonergic and noradrenergic mechanisms by blocking serotonin......-noradrenaline reuptake sites. We tested the hypothesis in patients with Parkinson's disease in whom we had measured the changes of blood flow everywhere in the brain associated with the deep brain stimulation of the subthalamic nucleus. We determined the emotional reactivity of the patients as the average impact...

  16. No effect of angiotensin II AT(2)-receptor antagonist PD 123319 on cerebral blood flow autoregulation

    DEFF Research Database (Denmark)

    Estrup, T M; Paulson, O B; Strandgaard, S

    2001-01-01

    Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin AT1-receptor antagonists shift the limits of autoregulation of cerebral blood flow (CBF) towards lower blood pressure (BP). The role of AT2-receptors in the regulation of the cerebral...... group. CBF was measured by the intracarotid 133xenon injection method and BP was raised by noradrenaline infusion and lowered by controlled haemorrhage in separate groups of rats. The limits of autoregulation were determined by computed least-sum-of-squares analysis. PD 123319 did not influence baseline...

  17. Autonomic response to an experimental psychological stressor in healthy subjects: measurement of sympathetic, parasympathetic, and pituitary-adrenal parameters: test-retest reliability

    DEFF Research Database (Denmark)

    Jørgensen, L S; Christiansen, P; Raundahl, U

    1990-01-01

    A mental arithmetic test (the stressor; 15 min) significantly increased systolic and diastolic blood pressure, heart rate and plasma adrenaline by 11%, 12%, 28% and 152% respectively, with a prompt return to resting values after the test. Plasma noradrenaline and serum cortisol did not increase...... of the stressor. As a measure of parasympathetic nervous function, the beat-to-beat variation of heart rate, expressed as the mean successive square difference (MSSD), was employed. Four to 14 months later, the investigation was repeated, and resting values of all measures were found to be stable. The increments...

  18. Catecholamines of the body tissues and radiosensitivity of rodents

    Energy Technology Data Exchange (ETDEWEB)

    Grayevskaya, V M; Zolotariova, N N [AN SSSR, Moscow. Inst. Morfologii Zhivotnykh

    1975-01-01

    Various species of rodents are distinguished by their radiosensitivity (increasing): bank vole < Wistar rat < wild mouse < CC/sub 57/Br mouse < golden hamster < BALB mouse < guinea pig. There is a positive correlation between radiosensitivity of these species and catecholamines content in the adrenals, urea and blood; and negative correlation between radiosensitivity and adrenaline and noradrenaline concentrations in liver and spleen cells. Presumable causes of this correlation, and the possibility of application of the index under study for predicting the organism radiosensitivity and forecasting the outcome of radiation damage are discussed.

  19. Sympathoadrenal activation and endotheliopathy are drivers of hypocoagulability and hyperfibrinolysis in trauma

    DEFF Research Database (Denmark)

    Ostrowski, Sisse R; Henriksen, Hanne Herborg; Stensballe, Jakob

    2017-01-01

    were drivers of this condition. METHODS: Prospective observational study of 404 trauma patients admitted to a Level 1 US Trauma Center. Patients with admission rTEG and plasma measurements of catecholamines (adrenaline, noradrenaline) and biomarkers reflecting endothelial activation/damage (syndecan-1......, which was associated with higher plasma adrenaline, syndecan-1, and nucleosomes (all adrenaline, s...... endothelial activation) were independently associated with more hypercoagulable rTEG. CONCLUSION: In this cohort of severely injured trauma patients, rTEG coagulopathy was associated with sympathoadrenal activation, endotheliopathy, and excess mortality. High adrenaline and biomarkers reflecting endothelial...

  20. High arterial compliance in cirrhosis is related to low adrenaline and elevated circulating calcitonin gene related peptide but not to activated vasoconstrictor systems

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Møller, S; Schifter, S

    2001-01-01

    catecholamines, renin activity, endothelin-1, and calcitonin gene related peptide (CGRP) at baseline and during oxygen inhalation. RESULTS: COMP(art) was significantly increased in cirrhotic patients compared with controls (1.32 v 1.06 ml/mm Hg; padrenaline levels (r=-0.......001) and central circulation time (r=-0.49; padrenaline (-16%; p... to COMP(art) disappeared. The relation of COMP(art) to CGRP and circulatory variables remained unchanged. CONCLUSION: Elevated arterial compliance in cirrhosis is related to low adrenaline, high CGRP, and systemic hyperdynamics but not to indicators of the activated vasoconstrictor systems (noradrenaline...

  1. BNP ist ANP, Endothelin und Noradrenalin als Prognoseindikator bei chronisch herzinsuffizienten Patienten überlegen

    OpenAIRE

    Zugck C; Gerhards A; Haass M; Katz N; Kell R; Krüger C; Schellberg D

    2001-01-01

    Zu den etablierten Prognoseindikatoren bei Patienten mit chronischer Herzinsuffizienz zählen der Herz-Thorax-Quotient in der Röntgen-Thoraxaufnahme (HTQ), die linksventrikuläre Ejektionsfraktion (LVEF) und die maximale Sauerstoffaufnahme unter Belastung (VO2max). Darüber hinaus wird zahlreichen neurohumoralen Parametern eine prognostische Wertigkeit zugeschrieben. An 166 Patienten mit chronischer Herzinsuffizienz (Alter 54 ± 9 Jahre; 70 % dilatative Kardiomyopathie; 30 % KHK; LVEF 21 ± 9 %) ...

  2. Association between intraoperative tissue oxygenation, arterial blood pressure and noradrenaline use in urological patients

    NARCIS (Netherlands)

    Spruit, R.J.; Schwarte, L.A.; Hakenberg, O.W.; Scheeren, T.

    2011-01-01

    Background and Goal of Study: Inadequate tissue oxygenation should be prevented during surgery as it might cause postoperative morbidity. In this observational study we looked at factors that might influence tissue oxygenation (StO2) such as blood pressure and use of vasoactive drugs. Materials and

  3. Orexin/Hypocretin and Organizing Principles for a Diversity of Wake-Promoting Neurons in the Brain.

    Science.gov (United States)

    Schöne, Cornelia; Burdakov, Denis

    2017-01-01

    An enigmatic feature of behavioural state control is the rich diversity of wake-promoting neural systems. This diversity has been rationalized as 'robustness via redundancy', wherein wakefulness control is not critically dependent on one type of neuron or molecule. Studies of the brain orexin/hypocretin system challenge this view by demonstrating that wakefulness control fails upon loss of this neurotransmitter system. Since orexin neurons signal arousal need, and excite other wake-promoting neurons, their actions illuminate nonredundant principles of arousal control. Here, we suggest such principles by reviewing the orexin system from a collective viewpoint of biology, physics and engineering. Orexin peptides excite other arousal-promoting neurons (noradrenaline, histamine, serotonin, acetylcholine neurons), either by activating mixed-cation conductances or by inhibiting potassium conductances. Ohm's law predicts that these opposite conductance changes will produce opposite effects on sensitivity of neuronal excitability to current inputs, thus enabling orexin to differentially control input-output gain of its target networks. Orexin neurons also produce other transmitters, including glutamate. When orexin cells fire, glutamate-mediated downstream excitation displays temporal decay, but orexin-mediated excitation escalates, as if orexin transmission enabled arousal controllers to compute a time integral of arousal need. Since the anatomical and functional architecture of the orexin system contains negative feedback loops (e.g. orexin ➔ histamine ➔ noradrenaline/serotonin-orexin), such computations may stabilize wakefulness via integral feedback, a basic engineering strategy for set point control in uncertain environments. Such dynamic behavioural control requires several distinct wake-promoting modules, which perform nonredundant transformations of arousal signals and are connected in feedback loops.

  4. Human Lymphatic Mesenteric Vessels: Morphology and Possible Function of Aminergic and NPY-ergic Nerve Fibers.

    Science.gov (United States)

    D'Andrea, Vito; Panarese, Alessandra; Taurone, Samanta; Coppola, Luigi; Cavallotti, Carlo; Artico, Marco

    2015-09-01

    The lymphatic vessels have been studied in different organs from a morphological to a clinical point of view. Nevertheless, the knowledge of the catecholaminergic control of the lymphatic circulation is still incomplete. The aim of this work is to study the presence and distribution of the catecholaminergic and NPY-ergic nerve fibers in the whole wall of the human mesenteric lymphatic vessels in order to obtain knowledge about their morphology and functional significance. The following experimental procedures were performed: 1) drawing of tissue containing lymphatic vessels; 2) cutting of tissue; 3) staining of tissue; 4) staining of nerve fibers; 5) histofluorescence microscopy for the staining of catecholaminergic nerve fibers; 6) staining of neuropeptide Y like-immune reactivity; 7) biochemical assay of proteins; 8) measurement of noradrenaline; 9) quantitative analysis of images; 10) statistical analysis of data. Numerous nerve fibers run in the wall of lymphatic vessels. Many of them are catecholaminergic in nature. Some nerve fibers are NPY-positive. The biochemical results on noradrenaline amounts are in agreement with morphological results on catecholaminergic nerve fibers. Moreover, the morphometric results, obtained by the quantitative analysis of images and the subsequent statistical analysis of data, confirm all our morphological and biochemical data. The knowledge of the physiological or pathological mechanism regulating the functions of the lymphatic system is incomplete. Nevertheless the catecholaminergic nerve fibers of the human mesenteric lymphatic vessels come from the adrenergic periarterial plexuses of the mesenterial arterial bed. NPY-ergic nerve fibers may modulate the microcirculatory mesenterial bed in different pathological conditions.

  5. Effect of Interleukin 1b on rat thymus microenvironment

    Directory of Open Access Journals (Sweden)

    M Artico

    2009-12-01

    Full Text Available The effect of interleukin 1b on the thymus of control and chemically sympathectomized adult and aged rats was studied with the aim of assessing the importance of adrenergic nerve fibres (ANF in the regulation of some immunological functions.The whole thymus was removed from normal, sympathectomized (with the neurotoxin 6-OH-dopamine and treated (interleukin 1b rats. Thymic slices were stained with eosin orange (for the recognition of microanatomical details of the thymic microenvironment and with Bodian’s method for staining of nerve fibres. Histofluorescence microscopy was employed for staining ANF and immunofluorescence was used for detecting NPY-like immunoreactivity. All images were submitted to quantitative morphometrical analysis and statistical analysis of data. Moreover, the amount of proteins and noradrenaline was measured on thymic homogenates. The results indicate that in normal conditions the formation of the thymic nerve plexi in the rat is complex: the majority of ANF are destroyed after chemical sympathectomy with 6-OH-dopamine and do not change after treatment with interleukin 1b; on the contrary, treatment with interleukin 1b induces substantial changes in the fresh weight of the thymus, the thymic microenvironment, thymic nerve fibers, ANF, NPY-like positive nerve fibres, and on the total amount of proteins and noradrenaline in rat thymic tissue homogenates.Immunostimulation with interleukin 1b induces substantial changes in the whole thymus, in its microenvironment and in ANF and NPY-like nerve fibres. After chemical sympathectomy, no significant immune response was evoked by interleukin 1b, since the majority of ANF was destroyed by chemical sympathectomy.

  6. Readmission of ICU patients: A quality indicator?

    Science.gov (United States)

    Woldhek, Annemarie L; Rijkenberg, Saskia; Bosman, Rob J; van der Voort, Peter H J

    2017-04-01

    Readmission rate is frequently proposed as a quality indicator because it is related to both patient outcome and organizational efficiency. Currently available studies are not clear about modifiable factors as tools to reduce readmission rate. In a 14year retrospective cohort study of 19,750 ICU admissions we identified 1378 readmissions (7%). A multivariate logistic regression analysis for determinants of readmission within 24h, 48h, 72h and any time during hospital admission was performed with adjustment for patients' characteristics and initial admission severity scores. In all models with different time points, patients with older age, a medical and emergency surgery initial admission and patients with higher SOFA score have a higher risk of readmission. Immunodeficiency was a predictor only in the at any time model. Confirmed infection was predicted in all models except the 24h model. Last day noradrenaline treatment was predicted in the 24 and 48h model. Mechanical ventilation on admission independently protected for readmission, which can be explained by the large number of cardiac surgery patients. All multivariate models had a moderate performance with the highest AUC of 0.70. Readmission can be predicted with moderate precision and independent variables associated with readmission are age, severity of disease, type of admission, infection, immunodeficiency and last day noradrenaline use. The latter factor is the only one that can be modified and therefore readmission rate does not meet the criteria to be used as a useful quality indicator. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. The metabolic trinity, glucose-glycogen-lactate, links astrocytes and neurons in brain energetics, signaling, memory, and gene expression.

    Science.gov (United States)

    Dienel, Gerald A

    2017-01-10

    Glucose, glycogen, and lactate are traditionally identified with brain energetics, ATP turnover, and pathophysiology. However, recent studies extend their roles to include involvement in astrocytic signaling, memory consolidation, and gene expression. Emerging roles for these brain fuels and a readily-diffusible by-product are linked to differential fluxes in glycolytic and oxidative pathways, astrocytic glycogen dynamics, redox shifts, neuron-astrocyte interactions, and regulation of astrocytic activities by noradrenaline released from the locus coeruleus. Disproportionate utilization of carbohydrate compared with oxygen during brain activation is influenced by catecholamines, but its physiological basis is not understood and its magnitude may be affected by technical aspects of metabolite assays. Memory consolidation and gene expression are impaired by glycogenolysis blockade, and prevention of these deficits by injection of abnormally-high concentrations of lactate was interpreted as a requirement for astrocyte-to-neuron lactate shuttling in memory and gene expression. However, lactate transport was not measured and evidence for presumed shuttling is not compelling. In fact, high levels of lactate used to preserve memory consolidation and induce gene expression are sufficient to shut down neuronal firing via the HCAR1 receptor. In contrast, low lactate levels activate a receptor in locus coeruleus that stimulates noradrenaline release that may activate astrocytes throughout brain. Physiological relevance of exogenous concentrations of lactate used to mimic and evaluate metabolic, molecular, and behavioral effects of lactate requires close correspondence with the normal lactate levels, the biochemical and cellular sources and sinks, and specificity of lactate delivery to target cells. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Monoaminergic integration of diet and social signals in the brains of juvenile spadefoot toads.

    Science.gov (United States)

    Burmeister, Sabrina S; Rodriguez Moncalvo, Verónica G; Pfennig, Karin S

    2017-09-01

    Social behavior often includes the production of species-specific signals (e.g. mating calls or visual displays) that evoke context-dependent behavioral responses from conspecifics. Monoamines are important neuromodulators that have been implicated in context-dependent social behavior, yet we know little about the development of monoaminergic systems and whether they mediate the effects of early life experiences on adult behavior. We examined the effects of diet and social signals on monoamines early in development in the plains spadefoot toad ( Spea bombifrons ), a species in which diet affects the developmental emergence of species recognition and body condition affects the expression of adult mating preferences. To do so, we manipulated the diet of juveniles for 6 weeks following metamorphosis and collected their brains 40 min following the presentation of either a conspecific or a heterospecific call. We measured levels of monoamines and their metabolites using high pressure liquid chromatography from tissue punches of the auditory midbrain (i.e. torus semicircularis), hypothalamus and preoptic area. We found that call type affected dopamine and noradrenaline signaling in the auditory midbrain and that diet affected dopamine and serotonin in the hypothalamus. In the preoptic area, we detected an interaction between diet and call type, indicating that diet modulates how the preoptic area integrates social information. Our results suggest that the responsiveness of monoamine systems varies across the brain and highlight preoptic dopamine and noradrenaline as candidates for mediating effects of early diet experience on later expression of social preferences. © 2017. Published by The Company of Biologists Ltd.

  9. Vaginocervical stimulation enhances social recognition memory in rats via oxytocin release in the olfactory bulb.

    Science.gov (United States)

    Larrazolo-López, A; Kendrick, K M; Aburto-Arciniega, M; Arriaga-Avila, V; Morimoto, S; Frias, M; Guevara-Guzmán, R

    2008-03-27

    The ability of vaginocervical stimulation (VCS) to promote olfactory social recognition memory at different stages of the ovarian cycle was investigated in female rats. A juvenile social recognition paradigm was used and memory retention tested at 30 and 300 min after an adult was exposed to a juvenile during three 4-min trials. Results showed that an intact social recognition memory was present at 30 min in animals with or without VCS and at all stages of the estrus cycle. However, whereas no animals in any stage of the estrus cycle showed retention of the specific recognition memory at 300 min, those in the proestrus/estrus phase that received VCS 10 min before the trial started did. In vivo microdialysis studies showed that there was a significant release of oxytocin after VCS in the olfactory bulb during proestrus. There was also increased oxytocin immunoreactivity within the olfactory bulb after VCS in proestrus animals compared with diestrus ones. Furthermore, when animals received an infusion of an oxytocin antagonist directly into the olfactory bulb, or a systemic administration of alpha or beta noradrenaline-antagonists, they failed to show evidence for maintenance of a selective olfactory recognition memory at 300 min. Animals with vagus or pelvic nerve section also showed no memory retention when tested after 300 min. These results suggest that VCS releases oxytocin in the olfactory bulb to enhance the social recognition memory and that this may be due to modulatory actions on noradrenaline release. The vagus and pelvic nerves are responsible for carrying the information from the pelvic area to the CNS.

  10. Role of α2-adrenoceptors in the lateral parabrachial nucleus in the control of body fluid homeostasis

    International Nuclear Information System (INIS)

    Andrade, C.A.F.; Andrade-Franzé, G.M.F.; De Paula, P.M.; De Luca, L.A. Jr.; Menani, J.V.

    2014-01-01

    Central α 2 -adrenoceptors and the pontine lateral parabrachial nucleus (LPBN) are involved in the control of sodium and water intake. Bilateral injections of moxonidine (α 2 -adrenergic/imidazoline receptor agonist) or noradrenaline into the LPBN strongly increases 0.3 M NaCl intake induced by a combined treatment of furosemide plus captopril. Injection of moxonidine into the LPBN also increases hypertonic NaCl and water intake and reduces oxytocin secretion, urinary sodium, and water excreted by cell-dehydrated rats, causing a positive sodium and water balance, which suggests that moxonidine injected into the LPBN deactivates mechanisms that restrain body fluid volume expansion. Pretreatment with specific α 2 -adrenoceptor antagonists injected into the LPBN abolishes the behavioral and renal effects of moxonidine or noradrenaline injected into the same area, suggesting that these effects depend on activation of LPBN α 2 -adrenoceptors. In fluid-depleted rats, the palatability of sodium is reduced by ingestion of hypertonic NaCl, limiting intake. However, in rats treated with moxonidine injected into the LPBN, the NaCl palatability remains high, even after ingestion of significant amounts of 0.3 M NaCl. The changes in behavioral and renal responses produced by activation of α 2 -adrenoceptors in the LPBN are probably a consequence of reduction of oxytocin secretion and blockade of inhibitory signals that affect sodium palatability. In this review, a model is proposed to show how activation of α 2 -adrenoceptors in the LPBN may affect palatability and, consequently, ingestion of sodium as well as renal sodium excretion

  11. Role of α{sub 2}-adrenoceptors in the lateral parabrachial nucleus in the control of body fluid homeostasis

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, C.A.F.; Andrade-Franzé, G.M.F.; De Paula, P.M.; De Luca, L.A. Jr.; Menani, J.V. [Departamento de Fisiologia e Patologia, Faculdade de Odontologia, Universidade Estadual Paulista, Araraquara, SP (Brazil)

    2014-01-10

    Central α{sub 2}-adrenoceptors and the pontine lateral parabrachial nucleus (LPBN) are involved in the control of sodium and water intake. Bilateral injections of moxonidine (α{sub 2}-adrenergic/imidazoline receptor agonist) or noradrenaline into the LPBN strongly increases 0.3 M NaCl intake induced by a combined treatment of furosemide plus captopril. Injection of moxonidine into the LPBN also increases hypertonic NaCl and water intake and reduces oxytocin secretion, urinary sodium, and water excreted by cell-dehydrated rats, causing a positive sodium and water balance, which suggests that moxonidine injected into the LPBN deactivates mechanisms that restrain body fluid volume expansion. Pretreatment with specific α{sub 2}-adrenoceptor antagonists injected into the LPBN abolishes the behavioral and renal effects of moxonidine or noradrenaline injected into the same area, suggesting that these effects depend on activation of LPBN α{sub 2}-adrenoceptors. In fluid-depleted rats, the palatability of sodium is reduced by ingestion of hypertonic NaCl, limiting intake. However, in rats treated with moxonidine injected into the LPBN, the NaCl palatability remains high, even after ingestion of significant amounts of 0.3 M NaCl. The changes in behavioral and renal responses produced by activation of α{sub 2}-adrenoceptors in the LPBN are probably a consequence of reduction of oxytocin secretion and blockade of inhibitory signals that affect sodium palatability. In this review, a model is proposed to show how activation of α{sub 2}-adrenoceptors in the LPBN may affect palatability and, consequently, ingestion of sodium as well as renal sodium excretion.

  12. Dynamics of blood flow: twenty years of achievement

    International Nuclear Information System (INIS)

    Rosendorff, C.

    1988-01-01

    The physiology of blood circulation has evolved from the descriptive phenomenology of William Harvey's time to an interdisciplinary science, involving elements of fluid dynamics, vessel wall mechanics, electrophysiology, cell biology, biochemistry and molecular biology. Most of these new developments have occured during the lifetime of the South African Medical Research Council. Highlights of the research undertaken by the Council regarding circulatory physiology are given. In the 1960s the use of xenon-133 to study the flow of blood to the brain resulted in the first systematic description of cerebral blood flow and its control by sympathetic nerves. During the 1970s this technique was refined and the use of radioactive microspheres for the measurement of tissue blood flow was developed. Research concerning the control of blood vessels in the kidney was also carried out, and this showed that the sympathetic nerves control renal blood flow by releasing a local hormone called renin. The renal release of renin was later recognised as being important in the control of blood pressure. Another development was the discovery that vascular sensitivity to noradrenaline was increased in certain types of liver diseases. An analysis of the blood of patients with obstructive jaundice showed that the substance responsible for this noradrenaline effect was a combination of cholesterol and lipo-protein. This led to the theory that excessive cholesterol in the blood may be dangerous. In the late 1970s a shift in research emphasis to coronary artery physiology occurred and the 1980s saw research move into the area of cell biology

  13. Application of cross-species PET imaging to assess neurotransmitter release in brain.

    Science.gov (United States)

    Finnema, Sjoerd J; Scheinin, Mika; Shahid, Mohammed; Lehto, Jussi; Borroni, Edilio; Bang-Andersen, Benny; Sallinen, Jukka; Wong, Erik; Farde, Lars; Halldin, Christer; Grimwood, Sarah

    2015-11-01

    This review attempts to summarize the current status in relation to the use of positron emission tomography (PET) imaging in the assessment of synaptic concentrations of endogenous mediators in the living brain. Although PET radioligands are now available for more than 40 CNS targets, at the initiation of the Innovative Medicines Initiative (IMI) "Novel Methods leading to New Medications in Depression and Schizophrenia" (NEWMEDS) in 2009, PET radioligands sensitive to an endogenous neurotransmitter were only validated for dopamine. NEWMEDS work-package 5, "Cross-species and neurochemical imaging (PET) methods for drug discovery", commenced with a focus on developing methods enabling assessment of changes in extracellular concentrations of serotonin and noradrenaline in the brain. Sharing the workload across institutions, we utilized in vitro techniques with cells and tissues, in vivo receptor binding and microdialysis techniques in rodents, and in vivo PET imaging in non-human primates and humans. Here, we discuss these efforts and review other recently published reports on the use of radioligands to assess changes in endogenous levels of dopamine, serotonin, noradrenaline, γ-aminobutyric acid, glutamate, acetylcholine, and opioid peptides. The emphasis is on assessment of the availability of appropriate translational tools (PET radioligands, pharmacological challenge agents) and on studies in non-human primates and human subjects, as well as current challenges and future directions. PET imaging directed at investigating changes in endogenous neurochemicals, including the work done in NEWMEDS, have highlighted an opportunity to further extend the capability and application of this technology in drug development.

  14. Lack of effect of the alpha2C-adrenoceptor Del322-325 polymorphism on inhibition of cyclic AMP production in HEK293 cells.

    Science.gov (United States)

    Montgomery, M D; Bylund, D B

    2010-02-01

    The alpha(2C)-adrenoceptor has multiple functions, including inhibiting release of noradrenaline from presynaptic nerve terminals. A human alpha(2C) polymorphism, Del322-325, a potential risk factor for heart failure, has been reported to exhibit reduced signalling in CHO cells. To further understand the role of the Del322-325 polymorphism on receptor signalling, we attempted to replicate and further study the reduced signalling in HEK293 cells. Human alpha(2C) wild-type (WT) and Del322-325 adrenoceptors were stably transfected into HEK293 cells. Radioligand binding was performed to determine affinities for both receptors. In intact cells, inhibition of forskolin-stimulated cyclic AMP production by WT and Del322-325 clones with a range of receptor densities (200-2320 fmol.mg(-1) protein) was measured following agonist treatment. Noradrenaline, brimonidine and clonidine exhibited similar binding affinities for WT and Del322-325. Brimonidine and clonidine also had similar efficacies and potencies for both receptors for the inhibition of cyclic AMP production at all receptor densities tested. A linear regression analysis comparing efficacy and potency with receptor expression levels showed no differences in slopes between WT and Del322-325. The alpha(2C) WT and Del322-325 adrenoceptors exhibited similar binding properties. Additionally, inhibition of cyclic AMP production by Del322-325 was similar to that of WT over a range of receptor densities. Therefore, in intact HEK293 cells, the alpha(2C)-Del322-325 polymorphism does not exhibit reduced signalling to adenylyl cyclase and may not represent a clinically important phenotype.

  15. Behavioural, neurochemical and neuroendocrine effects of the endogenous β-carboline harmane in fear-conditioned rats.

    Science.gov (United States)

    Smith, Karen L; Ford, Gemma K; Jessop, David S; Finn, David P

    2013-02-01

    The putative endogenous imidazoline binding site ligand harmane enhances neuronal activation in response to psychological stress and alters behaviour in animal models of anxiety and antidepressant efficacy. However, the neurobiological mechanisms underlying harmane's psychotropic effects are poorly understood. We investigated the effects of intraperitoneal injection of harmane (2.5 and 10 mg/kg) on fear-conditioned behaviour, hypothalamo-pituitary-adrenal axis activity, and monoaminergic activity within specific fear-associated areas of the rat brain. Harmane had no significant effect on the duration of contextually induced freezing or 22 kHz ultrasonic vocalisations and did not alter the contextually induced suppression of motor activity, including rearing. Harmane reduced the duration of rearing and tended to increase freezing in non-fear-conditioned controls, suggesting potential sedative effects. Harmane increased plasma ACTH and corticosterone concentrations, and serotonin (in hypothalamus, amygdaloid cortex, prefrontal cortex and hippocampus) and noradrenaline (prefrontal cortex) content, irrespective of fear-conditioning. Furthermore, harmane reduced dopamine and serotonin turnover in the PFC and hypothalamus, and serotonin turnover in the amygdaloid cortex in both fear-conditioned and non-fear-conditioned rats. In contrast, harmane increased dopamine and noradrenaline content and reduced dopamine turnover in the amygdala of fear-conditioned rats only, suggesting differential effects on catecholaminergic transmission in the presence and absence of fear. The precise mechanism(s) mediating these effects of harmane remain to be determined but may involve its inhibitory action on monoamine oxidases. These findings support a role for harmane as a neuromodulator, altering behaviour, brain neurochemistry and neuroendocrine function.

  16. [A case of minoxidil intoxication].

    Science.gov (United States)

    Takahashi, Tetsuya; Takei, Tetsuhiro; Ito, Toshitaka; Sakamoto, Kazunari; Nara, Takeshi; Yagi, Keiichi

    2014-09-01

    A 26-year-old man was found unable to move after oral consumption of 120 mL of RiUP X5® (containing 5 g/100 mL minoxidil) as a suicidal attempt. The patient complaining of frequent vomiting and weakness was transferred to our hospital. Findings on arrival: GCS E4V5M6; respiratory rate 24/ min; blood pressure 83/43 mmHg; pulse 152/min, regular; SpO₂97% (oxygen by mask: 6 L/min); thus, the patient was in shock. The systolic blood pressure and the pulse rate improved to about 90 mmHg and to about 130/min, respectively, in response to rapid intravenous infusion of 2,000 mL of lactated Ringer's solution. His circulatory condition tended to improve with parenteral fluid infusion alone. Forty hours after admission, however, heart failure developed due to excessive I.V. fluid infusion and abnormal body fluid distribution associated with delayed vascular smooth muscle relaxation; therefore, mechanical ventilation was initiated. Simultaneously, intravenous noradrenaline infusion was started because of a fall of the blood pressure. Subsequently, as the patient's respiratory and circulatory conditions gradually improved, he was weaned from mechanical ventilation, and the noradrenaline infusion was discontinued at 108 hours after admission. The patient made favorable progress and was discharged home on the 9th hospital day. Minoxidil exerts adverse effects mainly on the cardiovascular system. Since minoxidil is an over-the-counter drug readily available to the public, and emergency physicians should be aware of its severe toxicity.

  17. Linking Essential Tremor to the Cerebellum: Neurochemical Evidence.

    Science.gov (United States)

    Marin-Lahoz, Juan; Gironell, Alexandre

    2016-06-01

    The pathophysiology and the exact anatomy of essential tremor (ET) is not well known. One of the pillars that support the cerebellum as the main anatomical locus in ET is neurochemistry. This review examines the link between neurochemical abnormalities found in ET and cerebellum. The review is based on published data about neurochemical abnormalities described in ET both in human and in animal studies. We try to link those findings with cerebellum. γ-aminobutyric acid (GABA) is the main neurotransmitter involved in the pathophysiology of ET. There are several studies about GABA that clearly points to a main role of the cerebellum. There are few data about other neurochemical abnormalities in ET. These include studies with noradrenaline, glutamate, adenosine, proteins, and T-type calcium channels. One single study reveals high levels of noradrenaline in the cerebellar cortex. Another study about serotonin neurotransmitter results negative for cerebellum involvement. Finally, studies on T-type calcium channels yield positive results linking the rhythmicity of ET and cerebellum. Neurochemistry supports the cerebellum as the main anatomical locus in ET. The main neurotransmitter involved is GABA, and the GABA hypothesis remains the most robust pathophysiological theory of ET to date. However, this hypothesis does not rule out other mechanisms and may be seen as the main scaffold to support findings in other systems. We clearly need to perform more studies about neurochemistry in ET to better understand the relations among the diverse systems implied in ET. This is mandatory to develop more effective pharmacological therapies.

  18. Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis.

    Science.gov (United States)

    Tansey, Katherine E; Guipponi, Michel; Perroud, Nader; Bondolfi, Guido; Domenici, Enrico; Evans, David; Hall, Stephanie K; Hauser, Joanna; Henigsberg, Neven; Hu, Xiaolan; Jerman, Borut; Maier, Wolfgang; Mors, Ole; O'Donovan, Michael; Peters, Tim J; Placentino, Anna; Rietschel, Marcella; Souery, Daniel; Aitchison, Katherine J; Craig, Ian; Farmer, Anne; Wendland, Jens R; Malafosse, Alain; Holmans, Peter; Lewis, Glyn; Lewis, Cathryn M; Stensbøl, Tine Bryan; Kapur, Shitij; McGuffin, Peter; Uher, Rudolf

    2012-01-01

    It has been suggested that outcomes of antidepressant treatment for major depressive disorder could be significantly improved if treatment choice is informed by genetic data. This study aims to test the hypothesis that common genetic variants can predict response to antidepressants in a clinically meaningful way. The NEWMEDS consortium, an academia-industry partnership, assembled a database of over 2,000 European-ancestry individuals with major depressive disorder, prospectively measured treatment outcomes with serotonin reuptake inhibiting or noradrenaline reuptake inhibiting antidepressants and available genetic samples from five studies (three randomized controlled trials, one part-randomized controlled trial, and one treatment cohort study). After quality control, a dataset of 1,790 individuals with high-quality genome-wide genotyping provided adequate power to test the hypotheses that antidepressant response or a clinically significant differential response to the two classes of antidepressants could be predicted from a single common genetic polymorphism. None of the more than half million genetic markers significantly predicted response to antidepressants overall, serotonin reuptake inhibitors, or noradrenaline reuptake inhibitors, or differential response to the two types of antidepressants (genome-wide significance panalysis of NEWMEDS and another large sample (STAR*D), with 2,897 individuals in total. Polygenic scoring found no convergence among multiple associations in NEWMEDS and STAR*D. No single common genetic variant was associated with antidepressant response at a clinically relevant level in a European-ancestry cohort. Effects specific to particular antidepressant drugs could not be investigated in the current study. Please see later in the article for the Editors' Summary.

  19. Octopamine and Tyramine Contribute Separately to the Counter-Regulatory Response to Sugar Deficit in Drosophila

    Directory of Open Access Journals (Sweden)

    Christine Damrau

    2018-01-01

    Full Text Available All animals constantly negotiate external with internal demands before and during action selection. Energy homeostasis is a major internal factor biasing action selection. For instance, in addition to physiologically regulating carbohydrate mobilization, starvation-induced sugar shortage also biases action selection toward food-seeking and food consumption behaviors (the counter-regulatory response. Biogenic amines are often involved when such widespread behavioral biases need to be orchestrated. In mammals, norepinephrine (noradrenalin is involved in the counterregulatory response to starvation-induced drops in glucose levels. The invertebrate homolog of noradrenalin, octopamine (OA and its precursor tyramine (TA are neuromodulators operating in many different neuronal and physiological processes. Tyrosine-ß-hydroxylase (tßh mutants are unable to convert TA into OA. We hypothesized that tßh mutant flies may be aberrant in some or all of the counter-regulatory responses to starvation and that techniques restoring gene function or amine signaling may elucidate potential mechanisms and sites of action. Corroborating our hypothesis, starved mutants show a reduced sugar response and their hemolymph sugar concentration is elevated compared to control flies. When starved, they survive longer. Temporally controlled rescue experiments revealed an action of the OA/TA-system during the sugar response, while spatially controlled rescue experiments suggest actions also outside of the nervous system. Additionally, the analysis of two OA- and four TA-receptor mutants suggests an involvement of both receptor types in the animals' physiological and neuronal response to starvation. These results complement the investigations in Apis mellifera described in our companion paper (Buckemüller et al., 2017.

  20. Radioligand binding analysis of α 2 adrenoceptors with [11C]yohimbine in brain in vivo: Extended Inhibition Plot correction for plasma protein binding

    DEFF Research Database (Denmark)

    Phan, Jenny-Ann; Landau, Anne M.; Jakobsen, Steen

    2017-01-01

    We describe a novel method of kinetic analysis of radioligand binding to neuroreceptors in brain in vivo, here applied to noradrenaline receptors in rat brain. The method uses positron emission tomography (PET) of [11C]yohimbine binding in brain to quantify the density and affinity of α 2...... Inhibition Plot introduced here yielded an estimate of the volume of distribution of non-displaceable ligand in brain tissue that increased with the increase of the free fraction of the radioligand in plasma. The resulting binding potentials of the radioligand declined by 50-60% in the presence of unlabeled...

  1. Selective depletion of spinal monoamines changes the rat soleus EMG from a tonic to a more phasic pattern

    DEFF Research Database (Denmark)

    Kiehn, Ole; Erdal, Jesper; Eken, Torsten

    1996-01-01

    subarachnoid space and gross-EMG recording electrodes in the soleus muscle. EMG recordings were performed in control conditions and at different times after intrathecal administration of either 40-55 μg 5,6-dihydroxytryptamine (5,6-DHT) and 40-55 μg 6-hydroxydopamine (6-OHDA) or 80 μg 5,7-dihydroxytryptamine...... (5,7-DHT) alone. The depletions were evaluated biochemically in brains and spinal cords after recordings. 3. In agreement with previous studies the intrathecal administration of neurotoxins caused a reduction of the noradrenaline (NA) and serotonin (5-HT) content of the lumbar spinal cord to about 2...

  2. [Activity of the sympatho-adrenal system in patients with hysterical psychopathy and psychasthenia].

    Science.gov (United States)

    Trunova, M M

    1978-01-01

    The paper is concerned with studies of the sympathoadrenal system activity by the indices of urine excretion of catecholamine and dofa in patients with hysterical and psychasthenic psychopathy. The disorders inherent in each of the groups are demonstrated. The patients with hysterical psychopathy show an exhaustion of all links in the catecholamine metabolism, while the patients with psychasthenical psychopathy an exhaustion of the noradrenaline link. In attempting to explain the mechanisms of disturbed activity in the sympathoadrenal system in both groups the role of the functional state of nonspecific activizing brain systems was taken into consideration.

  3. Lu AA21004, a novel multimodal antidepressantwith activity exerted through serotonergic targets

    DEFF Research Database (Denmark)

    Mork, A.; Pehrson, A.; Montezinho, L. C. P.

    2012-01-01

    Background: Lu AA21004 is a multimodal antidepressant that functions as a 5-HT3 and 5-HT7 receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and inhibitor of the 5-HT transporter in vitro. Here we investigated preclinical effects of Lu AA21004 1) on target occupancies, 2...... (5-HT), noradrenaline (NA), dopamine (DA), acetylcholine (ACh), histamine (Hist)] were measured by microdialysis. Antidepressant potential was assessed in the forced swim test using Flinders Sensitive Line (FSL) rats. Moreover, effects of Lu AA21004 on acquisition, consolidation and recall...

  4. Effects of South African traditional medicine in animal models for depression

    DEFF Research Database (Denmark)

    Pedersen, Mikael Egebjerg; Szewczyk, Bernadeta; Stachowicz, Katarzyna

    2008-01-01

    in models for depression. MATERIALS AND METHODS: The extracts were screened for affinity for the serotonin transporter (SERT) in the [(3)H]-citalopram-binding assay. The inhibitory potency of the extracts towards the SERT, the noradrenalin transporter (NAT) and the dopamine transporter (DAT) were determined...... in a functional uptake inhibition assay. Antidepressant-like effects of the extracts were investigated using the tail suspension test (TST) and the forced swim test in both rats (rFST) and mice (mFST). RESULTS: All four plants showed affinity for SERT in the binding assay. AC and BD showed functional inhibition...

  5. Inducement of radionuclides targeting therapy by gene transfection

    International Nuclear Information System (INIS)

    Luo Quanyong

    2001-01-01

    The author presents an overview of gene transfection methods to genetically induce tumor cells to express enhanced levels of cell surface antigens and receptors to intake radiolabeled antibody and peptide targeting and thus increase their therapeutic effect in radiotherapy. The current research include inducement of radioimmunotherapy through CEA gene transfection, inducement of iodine-131 therapy by sodium iodide symporter gene transfection and inducement of MIBG therapy by noradrenaline transporter gene transfection. These studies raise the prospect that gene-therapy techniques could be used to enable the treatment of a wide range of tumors with radiopharmaceuticals of established clinical acceptability

  6. Rotational Spectroscopy Unveils Eleven Conformers of Adrenaline

    Science.gov (United States)

    Cabezas, C.; Cortijo, V.; Mata, S.; Lopez, J. C.; Alonso, J. L.

    2013-06-01

    Recent improvements in our LA-MB-FTMW instrumentation have allowed the characterization of eleven and eight conformers for the neurotransmitters adrenaline and noradrenaline respectively. The observation of this rich conformational behavior is in accordance with the recent observation of seven conformers for dopamine and in sharp contrast with the conformational reduction proposed for catecholamines. C. Cabezas, I. Peña, J. C. López, J. L. Alonso J. Phys. Chem. Lett. 2013, 4, 486. H. Mitsuda, M. Miyazaki, I. B. Nielsen, P. Carcabal,C. Dedonder, C. Jouvet, S. Ishiuchi, M. Fujii J. Phys. Chem. Lett. 2010, 1, 1130.

  7. Effects of noradrenaline on locomotor rhythm-generating networks in the isolated neonatal rat spinal cord

    DEFF Research Database (Denmark)

    Kiehn, O; Sillar, K T; Kjaerulff, O

    1999-01-01

    locomotor-like rhythm, in which activity alternated between the left and right sides, and between rostral and caudal roots on the same side. As shown previously, stable locomotor activity could be induced by bath application of N-methyl-D-aspartate (NMDA; 4-8.5 microM) and/or serotonin (5-HT; 4-20 micro......M). NA modulated this activity by decreasing the cycle frequency and increasing the ventral root burst duration. These effects were dose dependent in the concentration range 1-5 microM. In contrast, at no concentration tested did NA have consistent effects on burst amplitudes or on the background...... activity of the ongoing rhythm. Moreover, NA did not obviously affect the left/right and rostrocaudal alternation of the NMDA/5-HT rhythm. The NMDA/5-HT locomotor rhythm sometimes displayed a time-dependent breakdown in coordination, ultimately resulting in tonic ventral root activity. However...

  8. ABNORMAL PLASMA NORADRENALINE RESPONSE AND EXERCISE INDUCED ALBUMINURIA IN TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS

    NARCIS (Netherlands)

    HOOGENBERG, K; DULLAART, RPF

    1992-01-01

    Submaximal exercise provokes an abnormal elevation in albuminuria in type 1 (insulin-dependent) diabetes mellitus. Plasma catecholamines might be involved in this phenomenon by a renal vasoconstrictive effect. Twelve healthy subjects (Controls: albuminuria It is concluded that the exercise-induced

  9. Interaction of the endocrine system with inflammation: a function of energy and volume regulation.

    Science.gov (United States)

    Straub, Rainer H

    2014-02-13

    During acute systemic infectious disease, precisely regulated release of energy-rich substrates (glucose, free fatty acids, and amino acids) and auxiliary elements such as calcium/phosphorus from storage sites (fat tissue, muscle, liver, and bone) are highly important because these factors are needed by an energy-consuming immune system in a situation with little or no food/water intake (sickness behavior). This positively selected program for short-lived infectious diseases is similarly applied during chronic inflammatory diseases. This review presents the interaction of hormones and inflammation by focusing on energy storage/expenditure and volume regulation. Energy storage hormones are represented by insulin (glucose/lipid storage and growth-related processes), insulin-like growth factor-1 (IGF-1) (muscle and bone growth), androgens (muscle and bone growth), vitamin D (bone growth), and osteocalcin (bone growth, support of insulin, and testosterone). Energy expenditure hormones are represented by cortisol (breakdown of liver glycogen/adipose tissue triglycerides/muscle protein, and gluconeogenesis; water retention), noradrenaline/adrenaline (breakdown of liver glycogen/adipose tissue triglycerides, and gluconeogenesis; water retention), growth hormone (glucogenic, lipolytic; has also growth-related aspects; water retention), thyroid gland hormones (increase metabolic effects of adrenaline/noradrenaline), and angiotensin II (induce insulin resistance and retain water). In chronic inflammatory diseases, a preponderance of energy expenditure pathways is switched on, leading to typical hormonal changes such as insulin/IGF-1 resistance, hypoandrogenemia, hypovitaminosis D, mild hypercortisolemia, and increased activity of the sympathetic nervous system and the renin-angiotensin-aldosterone system. Though necessary during acute inflammation in the context of systemic infection or trauma, these long-standing changes contribute to increased mortality in chronic

  10. Quantification of extracellular levels of corticosterone in the basolateral amygdaloid complex of freely-moving rats: a dialysis study of circadian variation and stress-induced modulation.

    Science.gov (United States)

    Bouchez, Gaëlle; Millan, Mark J; Rivet, Jean-Michel; Billiras, Rodolphe; Boulanger, Raphaël; Gobert, Alain

    2012-05-03

    Corticosterone influences emotion and cognition via actions in a diversity of corticolimbic structures, including the amygdala. Since extracellular levels of corticosterone in brain have rarely been studied, we characterized a specific and sensitive enzymatic immunoassay for microdialysis quantification of corticosterone in the basolateral amygdaloid complex of freely-moving rats. Corticosterone levels showed marked diurnal variation with an evening (dark phase) peak and stable, low levels during the day (light phase). The "anxiogenic agents", FG7142 (20 mg/kg) and yohimbine (10 mg/kg), and an environmental stressor, 15-min forced-swim, induced marked and sustained (1-3 h) increases in dialysis levels of corticosterone in basolateral amygdaloid complex. They likewise increased dialysis levels of dopamine and noradrenaline, but not serotonin and GABA. As compared to basal corticosterone levels of ~200-300 pg/ml, the elevation provoked by forced-swim was ca. 20-fold and this increase was abolished by adrenalectomy. Interestingly, stress-induced rises of corticosterone levels in basolateral amygdaloid complex were abrogated by combined but not separate administration of the corticotrophin releasing factor(1) (CRF(1)) receptor antagonist, CP154,526, and the vasopressin(1b) (V(1b)) receptor antagonist, SSR149,415. Underpinning their specificity, they did not block forced-swim-induced elevations in dopamine and noradrenaline. In conclusion, extracellular levels of corticosterone in the basolateral amygdaloid complex display marked diurnal variation. Further, they are markedly elevated by acute stressors, the effects of which are mediated (in contrast to concomitant elevations in levels of monoamines) by co-joint recruitment of CRF(1) and V(1b) receptors. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. The effect of normobaric hypoxic confinement on metabolism, gut hormones and body composition

    Directory of Open Access Journals (Sweden)

    Igor B. Mekjavic

    2016-06-01

    Full Text Available To assess the effect of normobaric hypoxia on metabolism, gut hormones and body composition, eleven normal weight, aerobically trained ( O2peak: 60.6±9.5 ml·kg-1·min-1 men (73.0±7.7 kg; 23.7±4.0 yrs, BMI 22.2±2.4 kg·m-2 were confined to a normobaric (altitude⋍940m normoxic (NORMOXIA; PIO2⋍133.2 mmHg or normobaric hypoxic (HYPOXIA; PIO was reduced from 105.6 to 97.7 mmHg over 10 days environment for 10 days in a randomized cross-over design. The wash-out period between confinements was 3 weeks. During each 10-day period, subjects avoided strenuous physical activity and were under continuous nutritional control. Before, and at the end of each exposure, subjects completed a meal tolerance test, during which blood glucose, insulin, GLP-1, ghrelin, peptide-YY, adrenaline, noradrenaline, leptin, and gastro-intestinal blood flow and appetite sensations were measured. There was no significant change in body weight in either of the confinements (NORMOXIA: -0.7±0.2 kg; HYPOXIA: -0.9±0.2 kg, but a significant increase in fat mass in NORMOXIA (0.23±0.45 kg, but not in HYPOXIA (0.08±0.08 kg. HYPOXIA confinement increased fasting noradrenaline and decreased energy intake, the latter most likely associated with increased fasting leptin. The majority of all other measured variables/responses were similar in NORMOXIA and HYPOXIA. To conclude, normobaric hypoxic confinement without exercise training results in negative energy balance due to primarily reduced energy intake.

  12. (-)1-(Benzofuran-2-yl)-2-propylaminopentane, [(-)BPAP], a selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain.

    Science.gov (United States)

    Knoll, J; Yoneda, F; Knoll, B; Ohde, H; Miklya, I

    1999-12-01

    1. The brain constituents beta-phenylethylamine (PEA) and tryptamine enhance the impulse propagation mediated transmitter release (exocytosis) from the catecholaminergic and serotoninergic neurons in the brain ('catecholaminergic/serotoninergic activity enhancer, CAE/SAE, effect'). (-)Deprenyl (Selegiline) and (-)1-phenyl-2-propylaminopentane [(-)PPAP] are amphetamine derived CAE substances devoid of the catecholamine releasing property. 2. By changing the aromatic ring in PPAP we developed highly potent and selective CAE/SAE substances, structurally unrelated to the amphetamines. Out of 65 newly synthetized compounds, a tryptamine derived structure, (-)1-(benzofuran-2-yl)-2-propylaminopentane [(-)BPAP] was selected as a potential follower of (-)deprenyl in the clinic and as a reference compound for further analysis of the CAE/SAE mechanism in the mammalian brain. 3. (-)BPAP significantly enhanced in 0.18 micromol 1(-1) concentration the impulse propagation mediated release of [(3)H]-noradrenaline and [(3)H]-dopamine and in 36 nmol 1(-1) concentration the release of [(3)H]-serotonin from the isolated brain stem of rats. The amount of catecholamines and serotonin released from isolated discrete rat brain regions (dopamine from the striatum, substantia nigra and tuberculum olfactorium, noradrenaline from the locus coeruleus and serotonin from the raphe) enhanced significantly in the presence of 10(-12) - 10(-14) M (-)BPAP. BPAP protected cultured hippocampal neurons from the neurotoxic effect of beta-amyloid in 10(-14) M concentration. In rats (-)BPAP significantly enhanced the activity of the catecholaminergic and serotoninergic neurons in the brain 30 min after acute injection of 0.1 microg kg(-1) s.c. In the shuttle box, (-)BPAP in rats was about 130 times more potent than (-)deprenyl in antagonizing tetrabenazine induced inhibition of performance.

  13. Reflections on glycogen and β-amyloid: why does glycogenolytic β2-adrenoceptor stimulation not rescue memory after β-amyloid?

    Science.gov (United States)

    Gibbs, Marie

    2015-02-01

    Normally noradrenaline release ~30 min after training in the day-old chick is essential for memory consolidation by simultaneously increasing both glycogenolysis, by its stimulation of β2-adrenergic (AR) receptors, and glycogen synthesis, by its stimulation of α2-AR receptors in astrocytes. At the same time noradrenaline stimulation of β3-AR receptors increases glucose uptake solely in astrocytes. Intracerebral injection of small oligomeric β-amyloid protein (Aβ1-42) (Aβ) 45 min before one-trial bead discrimination learning in day-old chicks abolishes consolidation of memory 30 min post-learning. The ensuing memory loss can be rescued by injection of selective β3- and β(2-AR agonists (CL316243 and zinterol), which also have the ability to consolidate weakly-reinforced learning into long-term memory. However, although CL316243 rescues Aβ-induced memory loss over a similar time period to when it consolidates weak learning (up to 25 min post training), zinterol is effective over a more limited time period and unexpectedly it does not rescue at the time it promotes glycogenolysis. Injection of Aβ into the hippocampus and the locus coeruleus (LoC) also produces similar memory deficits and injection of both AR agonists into a cortical area can rescue memory from LoC Aβ. We have previously shown that β3-AR stimulation increases astrocytic glucose uptake and have suggested there may be sensitization or upregulation of the receptor. Since β2-AR stimulation does not rescue memory at the time it promotes glycogenolysis, but the receptor does not appear to be impaired, it is suggested that Aβ may be causing an impairment in the synthesis of readily available glycogen.

  14. Myocardial pre-synaptic sympathetic function correlates with glucose uptake in the failing human heart

    International Nuclear Information System (INIS)

    Mongillo, Marco; Leccisotti, Lucia; John, Anna S.; Pennell, Dudley J.; Camici, Paolo G.

    2007-01-01

    We have previously shown that the myocardium of patients with heart failure (HF) is insulin resistant. Chronic β-adrenergic stimulation has been implicated in insulin resistance in cultured cardiomyocytes in vitro, where sustained noradrenaline stimulation inhibited insulin-modulated glucose uptake. As the failing heart is characterized by increased sympathetic drive, we hypothesized that there is a correlation between pre-synaptic sympathetic function and insulin sensitivity in the myocardium of patients with HF. Eight patients (aged 67 ± 7 years) with coronary artery disease and left ventricular dysfunction (ejection fraction 44 ± 10%) underwent function and viability assessment with cardiovascular magnetic resonance. Myocardial glucose utilization (MGU) was measured using positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG). Pre-synaptic noradrenaline re-uptake was measured by calculating [ 11 C]meta-hydroxy-ephedrine (HED) volume of distribution (V d ) with PET. Two groups of healthy volunteers served as controls for the FDG (n = 8, aged 52 ± 4 years, p -1 .g -1 ) and dysfunctional (0.49 ± 0.14 μmol.min -1 .g -1 ) segments compared with controls (0.61 ± 0.7 μmol.min -1 .g -1 ; p d was reduced in dysfunctional segments of patients (38.9 ± 21.2 ml.g -1 ) compared with normal segments (52.2 ± 19.6 ml.g -1 ) and compared with controls (62.7 ± 11.3 ml.g -1 ). In patients, regional MGU was correlated with HED V d . The results of this study provide novel evidence of a correlation between cardiac sympathetic function and insulin sensitivity, which may represent one of the mechanisms contributing to insulin resistance in failing human hearts. (orig.)

  15. Evaluation of anti-obesity activity of duloxetine in comparison with sibutramine along with its anti-depressant activity: an experimental study in obese rats.

    Science.gov (United States)

    Chudasama, H P; Bhatt, P A

    2009-11-01

    5-HT and noradrenaline are important neurotransmitters that control increase in body mass and are involved in the pathophysiology of obesity and depression. Sibutramine, an established anti-obesity agent, and duloxetine, an anti-depressant agent, are serotonin noradrenaline reuptake inhibitors (SNRIs). The objective of the present study was to compare the anti-obesity effect of duloxetine with sibutramine along with its effect on blood pressure and depression in obese rats. The secondary objective of the study was to determine if a relationship exists between obesity and depression. Obesity was induced by high-fat diet (HFD) in healthy male Sprague-Dawley rats. After 5 weeks of feeding HFD, animals were overweight (17.57%) with high food intake (57.15%) in comparison with normal animals. These obese animals were treated with duloxetine (30 mg x kg(-1), p.o.) and sibutramine (5 mg x kg(-1), p.o.) for 4 weeks. Control animals were treated with duloxetine alone (30 mg x kg(-1), p.o.). Our results depict that duloxetine was as effective as sibutramine in reducing food intake, body mass, and relative adiposity, and increasing rectal temperature with an added advantage of decreasing blood pressure, which sibutramine failed to do. Besides reduction in body mass, unlike sibutramine, duloxetine improved depressive state as evaluated by despair swimming test, tail suspension test, and open field test, speculating its use as an anti-obesity agent in obese-depressive animals. Since obese control animals reflected decreased locomotor activity, a positive relationship can be speculated to exist between obesity and depression. Further studies on various antidepressant models are required to confirm this relationship.

  16. Improving Response Inhibition in Parkinson’s Disease with Atomoxetine

    Science.gov (United States)

    Ye, Zheng; Altena, Ellemarije; Nombela, Cristina; Housden, Charlotte R.; Maxwell, Helen; Rittman, Timothy; Huddleston, Chelan; Rae, Charlotte L.; Regenthal, Ralf; Sahakian, Barbara J.; Barker, Roger A.; Robbins, Trevor W.; Rowe, James B.

    2015-01-01

    Background Dopaminergic drugs remain the mainstay of Parkinson’s disease therapy but often fail to improve cognitive problems such as impulsivity. This may be due to the loss of other neurotransmitters, including noradrenaline, which is linked to impulsivity and response inhibition. We therefore examined the effect of the selective noradrenaline reuptake inhibitor atomoxetine on response inhibition in a stop-signal paradigm. Methods This pharmacological functional magnetic resonance imaging study used a double-blinded randomized crossover design with low-frequency inhibition trials distributed among frequent Go trials. Twenty-one patients received 40 mg atomoxetine or placebo. Control subjects were tested on no-drug. The effects of disease and drug on behavioral performance, regional brain activity, and functional connectivity were analyzed using general linear models. Anatomical connectivity was examined using diffusion-weighted imaging. Results Patients with Parkinson’s disease had longer stop-signal reaction times, less stop-related activation in the right inferior frontal gyrus (RIFG), and weaker functional connectivity between the RIFG and striatum compared with control subjects. Atomoxetine enhanced stop-related RIFG activation in proportion to disease severity. Although there was no overall behavioral benefit from atomoxetine, analyses of individual differences revealed that enhanced response inhibition by atomoxetine was associated with increased RIFG activation and functional frontostriatal connectivity. Improved performance was more likely in patients with higher structural frontostriatal connectivity. Conclusions This study suggests that enhanced prefrontal cortical activation and frontostriatal connectivity by atomoxetine may improve response inhibition in Parkinson’s disease. These results point the way to new stratified clinical trials of atomoxetine to treat impulsivity in selected patients with Parkinson’s disease. PMID:24655598

  17. Improving response inhibition in Parkinson's disease with atomoxetine.

    Science.gov (United States)

    Ye, Zheng; Altena, Ellemarije; Nombela, Cristina; Housden, Charlotte R; Maxwell, Helen; Rittman, Timothy; Huddleston, Chelan; Rae, Charlotte L; Regenthal, Ralf; Sahakian, Barbara J; Barker, Roger A; Robbins, Trevor W; Rowe, James B

    2015-04-15

    Dopaminergic drugs remain the mainstay of Parkinson's disease therapy but often fail to improve cognitive problems such as impulsivity. This may be due to the loss of other neurotransmitters, including noradrenaline, which is linked to impulsivity and response inhibition. We therefore examined the effect of the selective noradrenaline reuptake inhibitor atomoxetine on response inhibition in a stop-signal paradigm. This pharmacological functional magnetic resonance imaging study used a double-blinded randomized crossover design with low-frequency inhibition trials distributed among frequent Go trials. Twenty-one patients received 40 mg atomoxetine or placebo. Control subjects were tested on no-drug. The effects of disease and drug on behavioral performance, regional brain activity, and functional connectivity were analyzed using general linear models. Anatomical connectivity was examined using diffusion-weighted imaging. Patients with Parkinson's disease had longer stop-signal reaction times, less stop-related activation in the right inferior frontal gyrus (RIFG), and weaker functional connectivity between the RIFG and striatum compared with control subjects. Atomoxetine enhanced stop-related RIFG activation in proportion to disease severity. Although there was no overall behavioral benefit from atomoxetine, analyses of individual differences revealed that enhanced response inhibition by atomoxetine was associated with increased RIFG activation and functional frontostriatal connectivity. Improved performance was more likely in patients with higher structural frontostriatal connectivity. This study suggests that enhanced prefrontal cortical activation and frontostriatal connectivity by atomoxetine may improve response inhibition in Parkinson's disease. These results point the way to new stratified clinical trials of atomoxetine to treat impulsivity in selected patients with Parkinson's disease. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  18. Atomoxetine effects on attentional bias to drug-related cues in cocaine dependent individuals.

    Science.gov (United States)

    Passamonti, Luca; Luijten, M; Ziauddeen, H; Coyle-Gilchrist, I T S; Rittman, T; Brain, S A E; Regenthal, R; Franken, I H A; Sahakian, B J; Bullmore, E T; Robbins, T W; Ersche, K D

    2017-08-01

    Biased attention towards drug-related cues and reduced inhibitory control over the regulation of drug-intake characterize drug addiction. The noradrenaline system has been critically implicated in both attentional and response inhibitory processes and is directly affected by drugs such as cocaine. We examined the potentially beneficial effects of the noradrenaline reuptake inhibitor atomoxetine in improving cognitive control during two tasks that used cocaine- and non-cocaine-related stimuli. A double-blind, placebo-controlled, and cross-over psycho-pharmacological design was employed. A single oral dose of atomoxetine (40 mg) was administered to 28 cocaine-dependent individuals (CDIs) and 28 healthy controls. All participants performed a pictorial attentional bias task involving both cocaine- and non-cocaine-related pictures as well as a verbal go/no-go task composed of cocaine- and food-related words. As expected, CDIs showed attentional bias to cocaine-related cues whilst controls did not. More importantly, however, atomoxetine, relative to placebo, significantly attenuated attentional bias in CDIs (F 26  = 6.73, P = 0.01). During the go/no-go task, there was a treatment × trial × group interaction, although this finding only showed a trend towards statistical significance (F 26  = 3.38, P = 0.07). Our findings suggest that atomoxetine reduces attentional bias to drug-related cues in CDIs. This may result from atomoxetine's modulation of the balance between tonic/phasic activity in the locus coeruleus and the possibly parallel enhancement of noradrenergic neurotransmission within the prefrontal cortex. Studying how cognitive enhancers such as atomoxetine influence key neurocognitive indices in cocaine addiction may help to develop reliable biomarkers for patient stratification in future clinical trials.

  19. Selective labelling of dopamine (D2) receptors in rat striatum by [3H]domperidone but not by [3H]spiperone

    International Nuclear Information System (INIS)

    Lazareno, S.; Nahorski, S.R.

    1982-01-01

    Specific binding of [ 3 H]spiperone and [ 3 H]domperidone, displaceable by 1 μM d-butaclamol, was examined in rat striatal membranes. Initial saturation and displacement experiments indicated that [ 3 H]spiperone bound to more sites than [ 3 H]domperidone and that, whilst all displacing drugs were more potent against [ 3 H]domperidone, this difference in potency was greatest for dopamine agonists and specific antagonists and least for 5HT-related drugs. Sulpiride displaced [ 3 H]spiperone biphasically, and was used at a concentration of 50 μM to examine two classes of [ 3 H]spiperone binding: site 1 displaceable by sulpiride, and site 2 displaceable by butaclamol but not by sulpiride. Site 1 had twice the capacity of site 2 and ten times the affinity for [ 3 H]spiperone. Dopaminergic drugs displaced preferentially from site 1, whilst 5HT-related drugs were more potent against site 2. GTP reduced the potency of dopamine, noradrenaline and, to a lesser extent, 5HT at site 1, but had no effect at site 2. [ 3 H]Domperidone sites had the same capacity as [ 3 H]spiperone site 1, and dopamine, noradrenaline and 5HT, in the absence or presence of GTP, and sulpiride had essentially identical affinities for [ 3 H]domperidone sites and [ 3 H]spiperone site 1. It is concluded that [ 3 H]domperidone and [ 3 H]spiperone label an identical population of dopamine (D 2 ) receptors, whilst [ 3 H]spiperone also labels a substantial number of non-dopamine sites, at least some of which are 5TH-related. [ 3 H]Domperidone is the better radioligand for dopamine receptors. (Auth.)

  20. Catecholaminergic activation in acute myocardial infarction: time course and relation to left ventricular performance

    DEFF Research Database (Denmark)

    Petersen, Claus Leth; Nielsen, Jens Rokkedal; Petersen, Bodil Laub

    2003-01-01

    AIM: The study was designed to assess (1) the time course of catecholaminergic activation in acute myocardial infarction (AMI) as estimated by adrenaline (ADR) and noradrenaline (NOR) concentrations, and (2) to relate activation of these hormones to predict the outcome of cardiac performance......-ventricular ejection fraction (LVEF). RESULTS: In the study group as a whole, the concentrations of ADR decreased from (mean +/- SEM) 0.80 +/- 0.12 nmol/l on admission to 0.33 +/- 0.03 nmol/l at discharge (p ... of both ADR and NOR on admission were correlated to LVEF at discharge (r = -0.56, p ADR and NOR after 1 year follow-up was 0...

  1. Brain natriuretic peptide: Diagnostic potential in dogs

    Directory of Open Access Journals (Sweden)

    Spasojević-Kosić Ljubica

    2009-01-01

    Full Text Available The endocrine role of the heart is evident in the secretion of noradrenaline and natriuretic peptides. The secretion of natriuretic peptides presents a useful mechanism for different conditions of cardiac dysfunction. Brain natriuretic peptide (BNP has been accepted in human cardiology as a biomarker for cardiac insufficiency and coronary arterial disease. The specificity of the BNP structure is specie-specific, so that the testing of diagnostic and prognostic potential in dogs requires the existence of a test that is a homologue for that animal specie. The existence of an adequate method for measuring BNP concentration makes possible its implementation as a screening test in everyday clinical practice. .

  2. Neuroendocrine responses to hypoglycaemia decrease within the first year after diagnosis of type 1 diabetes

    DEFF Research Database (Denmark)

    Damholt, M B; Christensen, N J; Hilsted, Jannik

    2001-01-01

    within the normal range throughout the study. Altered neuroendocrine responses to hypoglycaemia may occur early in the course of type 1 diabetes. These are unlikely to be due to structural changes (i.e. autonomic neuropathy), but rather to changes in central nervous system activity patterns, i.......e. a higher threshold (i.e. a lower blood glucose level) for hypothalamic activation of the sympathoadrenal system.......Neuroendocrine responses (adrenaline, noradrenaline and pancreatic polypeptide (PP)) to hypoglycaemia are often diminished in long-term diabetic patients, but the role of autonomic nervous system changes in these reductions is not yet fully clarified. In order to establish whether such changes...

  3. Adipocyte triglyceride turnover and lipolysis in lean and overweight subjects.

    Science.gov (United States)

    Rydén, Mikael; Andersson, Daniel P; Bernard, Samuel; Spalding, Kirsty; Arner, Peter

    2013-10-01

    Human obesity is associated with decreased triglyceride turnover and impaired lipolysis in adipocytes. We determined whether such defects also occur in subjects with only moderate increase in fat mass. Human abdominal subcutaneous adipose tissue was investigated in healthy, nonobese subjects [body mass index (BMI) > 17 kg/m(2) and BMI lean subjects (P = 0.017) with triglyceride T1/2 of 14 and 9 months, respectively (P = 0.04). Triglyceride age correlated positively with BMI (P = 0.002) but not with adipocyte volume (P = 0.2). Noradrenaline-, isoprenaline- or dibutyryl cyclic AMP-induced lipolysis was inversely correlated with triglyceride age (P maintenance of excess body fat.

  4. Radionuclide therapy of Sipple syndrome using iodine-131 metaiodobenzylguanidine

    International Nuclear Information System (INIS)

    Furusawa, Mitsuhiro; Shimomura, Osamu; Tomiguchi, Seiji; Hirota, Yoshihisa; Takahashi, Mutsumasa; Yamauchi, Jyoji; Iwaoka, Daisuke; Satoh, Tatsuo

    1992-01-01

    A 40-years-old female who had lung and liver metastases from malignant pheochromocytoma was treated with 3.7 GBq 131 I-MIBG (metaiodobenzylguanidine). After the treatment, 131 I-MIBG showed increased uptake in the metastatic lesions of the lung and liver. The size of tumor was no significant change on CT and MRI, but the intensity of liver metastases decreased gradually on MRI. Prior to the treatment, the levels of adrenaline and noradrenaline were high. One to three days after treatment, the level of these laboratory data further increased, but they gradually decreased in 1 to 3 months. These changes may be due to necrosis of tumor tissue. (author)

  5. Endocrine, metabolic and cardiovascular responses to adrenaline after abdominal surgery

    DEFF Research Database (Denmark)

    Hilsted, J; Wilken-Jensen, Charlotte; Birch, K

    1990-01-01

    Adrenaline-induced changes in heart rate, blood pressure, plasma adrenaline and noradrenaline, cortisol, glucagon, insulin, cAMP, glucose lactate, glycerol and beta-hydroxybutyrate were studied preoperatively and 4 and 24 h after skin incision in 8 patients undergoing elective cholecystectomy. Late...... postoperative responses of blood glucose, plasma cAMP, lactate and glycerol to adrenaline infusion were reduced, whereas other responses were unaffected. Blood glucose appearance and disappearance rate as assessed by [3H]3-glucose infusion was unchanged pre- and postoperatively. The increase in glucose...... appearance rate following adrenaline was similar pre- and postoperatively. These findings suggest that several beta-receptor-mediated responses to adrenaline are reduced after abdominal surgery....

  6. Monoamines and sexual function in rats bred for increased catatonic reactivity.

    Science.gov (United States)

    Klochkov, D V; Alekhina, T A; Kuznetsova, E G; Barykina, N N

    2009-07-01

    Body weight, ovary and uterus weight, the nature of estral cycles, and hypothalamus dopamine and noradrenaline levels and plasma testosterone levels were studied in female GC rats, bred for increased catatonic reactivity, at different stages of the estral cycle (estrus, proestrus). The outbred Wistar strain served as controls. On the background of decreased body weight, GC females showed impairments to the morphological cyclical changes in the ovaries and uterus, with a reduction in ovary weight in diestrus (p rats showed higher levels of these monoamines in estrus and lower levels in diestrus. Plasma testosterone levels in female GC rats were higher in diestrus than in estrus and in Wistar rats.

  7. Changes in aminoacidergic and monoaminergic neurotransmission in the hippocampus and amygdala of rats after ayahuasca ingestion

    Institute of Scientific and Technical Information of China (English)

    Eduardo; Ferreira; de; Castro-Neto; Rafael; Henrique; da; Cunha; Dartiu; Xavier; da; Silveira; Mauricio; Yonamine; Telma; Luciana; Furtado; Gouveia; Esper; Abro; Cavalheiro; Débora; Amado; Maria; da; Graa; Naffah-Mazzacoratti

    2013-01-01

    AIM: To evaluate changes in neurotransmission induced by a psychoactive beverage ayahuasca in the hippocampus and amygdala of naive rats. METHODS: The level of monoamines, their main metabolites and amino acid neurotransmitters concentrations were quantified using high performance liquid chromatography(HPLC). Four groups of rats were employed: saline-treated and rats receiving 250, 500 and 800 mg/kg of ayahuasca infusion(gavage). Animals were killed 40 min after drug ingestion and the structures stored at-80 ℃ until HPLC assay. The data from all groups were compared using Analysis of variance and Scheffé as post test and P < 0.05 was accepted as significant. RESULTS: The results showed decreased concentrations of glycine(GLY)(0.13 ± 0.03 vs 0.29 ± 0.07, P < 0.001) and γ-aminobutyric acid(GABA)(1.07 ± 0.14 vs 1.73 ± 0.25, P < 0.001) in the amygdala of rats that received 500 of ayahuasca. Animals that ingested 800 mg/kg of ayahuasca also showed a reduction of GLY level(0.11 ± 0.01 vs 0.29 ± 0.07, P < 0.001) and GABA(0.98 ± 0.06 vs 1.73 ± 0.25, P < 0.001). In the hippocampus, increased GABA levels were found in rats that received all ayahuasca doses: 250 mg/kg(1.29 ± 0.19 vs 0.84 ± 0.21, P < 0.05); 500 mg/kg(2.23 ± 038 vs 084 ± 0.21, P < 0.05) and 800 mg/kg(1.98 ± 0.92 vs 0.84 ± 0.21, P < 0.05). In addition, an increased utilization rate of all monoamines was found in the amygdala after ayahuasca administration in doses: 250 mg/kg(noradrenaline: 0.16 ± 0.02 vs 0.36 ± 0.06, P < 0.01; dopamine: 0.39 ± 0.012 vs 2.39 ± 0.84, P < 0.001; serotonin: 1.02 ± 0.22 vs 4.04 ± 0.91, P < 0.001), 500 mg/kg(noradrenaline: 0.08 ± 0.02 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.33 ± 0.19 vs 2.39 ± 0.84, P < 0.001; serotonin: 0.59 ± 0.08 vs 4.04 ± 0.91, P < 0.001) and 800 mg/kg(noradrenaline: 0.16 ± 0.04 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.84 ± 0.65 vs2.39 ± 0.84, P < 0.05; serotonin: 0.36 ± 0.02 vs 4.04 ± 0.91, P < 0.001). CONCLUSION: Our data suggest

  8. Nicotine stimulates pancreatic cancer xenografts by systemic increase in stress neurotransmitters and suppression of the inhibitory neurotransmitter gamma-aminobutyric acid.

    Science.gov (United States)

    Al-Wadei, Hussein A N; Plummer, Howard K; Schuller, Hildegard M

    2009-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer mortality in Western countries. We have shown previously that four representative human PDAC cell lines were regulated by beta-adrenoreceptors via cyclic adenosine 3',5'-monophosphate (cAMP)-dependent signaling. In the current study, we have tested the hypothesis that nicotine stimulates the growth of PDAC xenografts in nude mice by increasing the systemic levels of the stress neurotransmitters adrenaline and noradrenaline, which are the physiological agonists for beta-adrenoreceptors and that inhibition by gamma-aminobutyric acid (GABA) of the adenylyl cyclase-dependent pathway downstream of adrenoreceptors blocks this effect. The size of xenografts from PDAC cell line Panc-1 was determined 30 days after inoculation of the cancer cells. Stress neurotransmitters in serum as well as cAMP in the cellular fraction of blood and in tumor tissue were assessed by immunoassays. Levels of GABA, its synthesizing enzymes GAD65 and GAD67 and beta-adrenergic signaling proteins in the tumor tissue were determined by western blotting. Nicotine significantly increased the systemic levels of adrenaline, noradrenaline and cAMP while increasing xenograft size and protein levels of cAMP, cyclic AMP response element-binding protein and p-extracellular signal-regulated kinase 1/2 in the tumor tissue. Nicotine additionally reduced the protein levels of both GAD isozymes and GABA in tumor tissue. Treatment with GABA abolished these responses to nicotine and blocked the development of xenografts in mice not exposed to nicotine. These findings suggest that the development and progression of PDAC is subject to significant modulation by stimulatory stress neurotransmitters and inhibitory GABA and that treatment with GABA may be useful for marker-guided cancer intervention of PDAC.

  9. Nicotinic receptor-associated modulation of stimulatory and inhibitory neurotransmitters in NNK-induced adenocarcinoma of the lungs and pancreas

    Science.gov (United States)

    Al-Wadei, Hussein A. N.; Schuller, Hildegard M.

    2012-01-01

    Small airway-derived pulmonary adenocarcinoma (PAC) and pancreatic ductal adenocarcinoma (PDAC) are among the most common human cancers and smoking is a risk factor for both. Emerging research has identified cAMP signaling stimulated by the stress neurotransmitters adrenaline and noradrenaline as important stimulators of several adenocarcinomas, including PAC and PDAC. The nicotine-derived nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent mutagen and the most powerful tobacco carcinogen. NNK is also an agonist for nicotinic acetylcholine receptors (nAChRs). Using hamster models of NNK-induced PAC and PDAC, we have tested the hypothesis that in analogy to chronic effects of nicotine in the brain, NNK may modulate the α7- and α4β2nAChRs, causing an increase in stress neurotransmitters and decrease in the inhibitory neurotransmitter γ-aminobutyric acid (GABA). In support of our hypothesis, immunoassays showed a significant increase in serum adrenaline/noradrenaline and increased intracellular cAMP in the cellular fraction of blood of NNK treated hamsters. Western blots were done with cells harvested by laser capture microcopy from control small airway epithelia, alveolar epithelia, pancreatic islet and pancreatic duct epithelia and from NNK-induced PACs and PDACs. The GABA synthesizing enzyme glutamate decarboxylase 65 (GAD65) and GABA were suppressed in NNK-induced PACs and PDACs whereas protein expression of the α7nAChR, α4nAChR as well as p-CREB and p-ERK1/2 were upregulated. These findings suggest, for the first time, that NNK-induced alterations in regulatory nAChRs may contribute to the development of smoking-associated PAC and PDAC by disturbing the balance between cancer stimulating and inhibiting neurotransmitters. PMID:19274673

  10. Effects of exercise training on stress-induced vascular reactivity alterations: role of nitric oxide and prostanoids

    Directory of Open Access Journals (Sweden)

    Thiago Bruder-Nascimento

    2015-06-01

    Full Text Available Background: Physical exercise may modify biologic stress responses. Objective: To investigate the impact of exercise training on vascular alterations induced by acute stress, focusing on nitric oxide and cyclooxygenase pathways. Method: Wistar rats were separated into: sedentary, trained (60-min swimming, 5 days/week during 8 weeks, carrying a 5% body-weight load, stressed (2 h-immobilization, and trained/stressed. Response curves for noradrenaline, in the absence and presence of L-NAME or indomethacin, were obtained in intact and denuded aortas (n=7-10. Results: None of the procedures altered the denuded aorta reactivity. Intact aortas from stressed, trained, and trained/stressed rats showed similar reduction in noradrenaline maximal responses (sedentary 3.54±0.15, stressed 2.80±0.10*, trained 2.82±0.11*, trained/stressed 2.97± 0.21*, *P<0.05 relate to sedentary. Endothelium removal and L-NAME abolished this hyporeactivity in all experimental groups, except in trained/stressed rats that showed a partial aorta reactivity recovery in L-NAME presence (L-NAME: sedentary 5.23±0,26#, stressed 5.55±0.38#, trained 5.28±0.30#, trained/stressed 4.42±0.41, #P<0.05 related to trained/stressed. Indomethacin determined a decrease in sensitivity (EC50 in intact aortas of trained rats without abolishing the aortal hyporeactivity in trained, stressed, and trained/stressed rats. Conclusions: Exercise-induced vascular adaptive response involved an increase in endothelial vasodilator prostaglandins and nitric oxide. Stress-induced vascular adaptive response involved an increase in endothelial nitric oxide. Beside the involvement of the endothelial nitric oxide pathway, the vascular response of trained/stressed rats involved an additional mechanism yet to be elucidated. These findings advance on the understanding of the vascular processes after exercise and stress alone and in combination.

  11. The effect of a 48 h fast on the thermoregulatory responses to graded cooling in man.

    Science.gov (United States)

    Macdonald, I A; Bennett, T; Sainsbury, R

    1984-10-01

    The thermoregulatory responses to graded cooling were measured in 11 healthy male subjects after a 12 h fast and after a 48 h fast. The cooling stimulus was produced by changing the temperature of the skin of the trunk and legs with a water-perfused suit. Five levels of skin temperature from 35.5 to 24 degrees C were applied on each occasion. After a 12 h fast, core temperature was maintained during cooling. This maintenance of core temperature was associated with an increase in metabolic rate and a reduction in blood flow to the hand and to the forearm. After 48 h of fasting, the subjects could not maintain core temperature during cooling, and a decrease of 0.36 +/- 0.05 degrees C occurred as the suit temperature was reduced from 35.9 to 24 degrees C. Metabolic rate was slightly higher after the 48 h fast than after the 12 h fast, but similar increases in metabolic rate were observed during cooling. Vasoconstriction in the hand was initially less after a 48 h fast than after a 12 h fast, but at the lowest suit temperature, hand blood flow was similar, and low, on both occasions. After 48 h of fasting, forearm blood flow was elevated at all suit temperatures, being approximately twice the level recorded after the 12 h fast. Venous plasma noradrenaline levels did not change during cooling after the 12 h fast, whilst after 48 h of fasting a significant increase in noradrenaline level was observed at the lowest suit temperature. The results of this study provide further evidence that fasting induces an impairment of autonomic reflex mechanisms, but it is not clear whether this is due to a suppression of sympathetic nervous activity.

  12. Effect of neonatal nociceptin or nocistatin imprinting on the brain concentration of biogenic amines and their metabolites.

    Science.gov (United States)

    Tekes, Kornélia; Gyenge, Melinda; Sótonyi, Péter; Csaba, György

    2009-04-01

    Noradrenaline (NA), dopamine (DA), homovanillic acid (HA), serotonin (5HT) and 5-hydroxyindole acetic acid (5HIAA) content of five brain regions (hypothalamus, hippocampus, brainstem, striatum and frontal cortex) and the cerebrospinal fluid (CSF) was measured in adult (three months old) male and female rats treated neonatally with a single dose of 10 microg nociceptin (NC) or 10 microg nocistatin (NS) for hormonal imprinting. The biogenic amine and metabolite content of cerebrospinal fluid was also determined. In NC treated animals the serotonergic, dopaminergic as well as noradrenergic systems were influenced by the imprinting. The 5HT level increased in hypothalamus, the 5HIAA tissue levels were found increased in hypothalamus. Hippocampus and striatum and the HVA levels increased highly significantly in brainstem. Dopamine level decreased significantly in striatum, however in frontal cortex both noradrenalin and 5HIAA level decreased. Nevertheless, in NS-treated rats decreased NA tissue levels were found in hypothalamus, brainstem and frontal cortex. Decreased DA levels were found in the hypothalamus, brainstem and striatum. NS imprinting resulted in decreased HVA level, but increased one in the brainstem. The 5HT levels decreased in the hypothalamus, brainstem, striatum and frontal cortex, while 5HIAA content of CSF, and frontal cortex decreased, and that of hypothalamus, hippocampus and striatum increased. There was no significant difference between genders except in the 5HT tissue levels of NC treated rats. Data presented show that neonatal imprinting both by NC and NS have long-lasting and brain area specific effects. In earlier experiments endorphin imprinting also influenced the serotonergic system suggesting that during labour release of pain-related substances may durably affect the serotonergic (dopaminergic, adrenergic) system which can impress the animals' later behavior.

  13. Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Katherine E Tansey

    Full Text Available It has been suggested that outcomes of antidepressant treatment for major depressive disorder could be significantly improved if treatment choice is informed by genetic data. This study aims to test the hypothesis that common genetic variants can predict response to antidepressants in a clinically meaningful way.The NEWMEDS consortium, an academia-industry partnership, assembled a database of over 2,000 European-ancestry individuals with major depressive disorder, prospectively measured treatment outcomes with serotonin reuptake inhibiting or noradrenaline reuptake inhibiting antidepressants and available genetic samples from five studies (three randomized controlled trials, one part-randomized controlled trial, and one treatment cohort study. After quality control, a dataset of 1,790 individuals with high-quality genome-wide genotyping provided adequate power to test the hypotheses that antidepressant response or a clinically significant differential response to the two classes of antidepressants could be predicted from a single common genetic polymorphism. None of the more than half million genetic markers significantly predicted response to antidepressants overall, serotonin reuptake inhibitors, or noradrenaline reuptake inhibitors, or differential response to the two types of antidepressants (genome-wide significance p<5×10(-8. No biological pathways were significantly overrepresented in the results. No significant associations (genome-wide significance p<5×10(-8 were detected in a meta-analysis of NEWMEDS and another large sample (STAR*D, with 2,897 individuals in total. Polygenic scoring found no convergence among multiple associations in NEWMEDS and STAR*D.No single common genetic variant was associated with antidepressant response at a clinically relevant level in a European-ancestry cohort. Effects specific to particular antidepressant drugs could not be investigated in the current study. Please see later in the article for the

  14. Possible Increase in Serum FABP4 Level Despite Adiposity Reduction by Canagliflozin, an SGLT2 Inhibitor.

    Directory of Open Access Journals (Sweden)

    Masato Furuhashi

    Full Text Available Fatty acid-binding protein 4 (FABP4/A-FABP/aP2 is secreted from adipocytes in association with catecholamine-induced lipolysis, and elevated serum FABP4 level is associated with obesity, insulin resistance and atherosclerosis. Secreted FABP4 as a novel adipokine leads to insulin resistance via increased hepatic glucose production (HGP. Sodium-glucose cotransporter 2 (SGLT2 inhibitors decrease blood glucose level via increased urinary glucose excretion, though HGP is enhanced. Here we investigated whether canagliflozin, an SGLT2 inhibitor, modulates serum FABP4 level.Canagliflozin (100 mg/day was administered to type 2 diabetic patients (n = 39 for 12 weeks. Serum FABP4 level was measured before and after treatment.At baseline, serum FABP4 level was correlated with adiposity, renal dysfunction and noradrenaline level. Treatment with canagliflozin significantly decreased adiposity and levels of fasting glucose and HbA1c but increased average serum FABP4 level by 10.3% (18.0 ± 1.0 vs. 19.8 ± 1.2 ng/ml, P = 0.008, though elevation of FABP4 level after treatment was observed in 26 (66.7% out of 39 patients. Change in FABP4 level was positively correlated with change in levels of fasting glucose (r = 0.329, P = 0.044, HbA1c (r = 0.329, P = 0.044 and noradrenaline (r = 0.329, P = 0.041 but was not significantly correlated with change in adiposity or other variables.Canagliflozin paradoxically increases serum FABP4 level in some diabetic patients despite amelioration of glucose metabolism and adiposity reduction, possibly via induction of catecholamine-induced lipolysis in adipocytes. Increased FABP4 level by canagliflozin may undermine the improvement of glucose metabolism and might be a possible mechanism of increased HGP by inhibition of SGLT2.UMIN-CTR Clinical Trial UMIN000018151.

  15. (−)1-(Benzofuran-2-yl)-2-propylaminopentane, [(−)BPAP], a selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain

    Science.gov (United States)

    Knoll, Joseph; Yoneda, Fumio; Knoll, Berta; Ohde, Hironori; Miklya, Ildikó

    1999-01-01

    The brain constituents β-phenylethylamine (PEA) and tryptamine enhance the impulse propagation mediated transmitter release (exocytosis) from the catecholaminergic and serotoninergic neurons in the brain (‘catecholaminergic/serotoninergic activity enhancer, CAE/SAE, effect'). (−)Deprenyl (Selegiline) and (−)1-phenyl-2-propylaminopentane [(−)PPAP] are amphetamine derived CAE substances devoid of the catecholamine releasing property.By changing the aromatic ring in PPAP we developed highly potent and selective CAE/SAE substances, structurally unrelated to the amphetamines. Out of 65 newly synthetized compounds, a tryptamine derived structure, (−)1-(benzofuran-2-yl)-2-propylaminopentane [(−)BPAP] was selected as a potential follower of (−)deprenyl in the clinic and as a reference compound for further analysis of the CAE/SAE mechanism in the mammalian brain.(−)BPAP significantly enhanced in 0.18 μmol 1−1 concentration the impulse propagation mediated release of [3H]-noradrenaline and [3H]-dopamine and in 36 nmol 1−1 concentration the release of [3H]-serotonin from the isolated brain stem of rats. The amount of catecholamines and serotonin released from isolated discrete rat brain regions (dopamine from the striatum, substantia nigra and tuberculum olfactorium, noradrenaline from the locus coeruleus and serotonin from the raphe) enhanced significantly in the presence of 10−12–10−14 M (−)BPAP. BPAP protected cultured hippocampal neurons from the neurotoxic effect of β-amyloid in 10−14 M concentration. In rats (−)BPAP significantly enhanced the activity of the catecholaminergic and serotoninergic neurons in the brain 30 min after acute injection of 0.1 μg kg−1 s.c. In the shuttle box, (−)BPAP in rats was about 130 times more potent than (−)deprenyl in antagonizing tetrabenazine induced inhibition of performance. PMID:10588928

  16. Development of temperature regulation in newborn reindeer

    Directory of Open Access Journals (Sweden)

    R. Hissa

    1981-05-01

    Full Text Available Development of temperature regulation was investigated by determining the ability of newborn reindeer calves (Rangifer tarandus tarandus to maintain a normal body temperature when exposed to an incrementially decreasing ambient temperature. Newborn calves (1 day old can maintain their body temperature even at -15 °C. They can increase their metabolic rate five- to sixfold. Heat production is primarily stimulated by the sympathetic nervous system. The response to exogenous administration of noradrenaline and propranolol was investigated.Poronvasan låmmonsååtelyn syntymånjålkeinen kehittyminen.Abstract in Finnish / Yhteenveto: Vastasyntyneiden poronvasojen kylmansietoa ja lammonsaatelya tutkittiin toukokuussa 1981 Inarin Kaamasessa Paliskuntain yhdistyksen koetarhassa. Tutkittavat vasat olivat 1-10 vuorokauden ikaisia. Vasa asetettiin jååhdytettåvaån mittauskammioon. Sen aineenvaihdunta, lampotilat niin ihon eri kohdista kuin perasuolesta, lihasvarina ja sydanfrekvenssi rekisteroitiin jatkuvasti. Tulosten mukaan nayttåa siltå kuin 1 vuorokauden ikaiselle vasalle -15 °C olisi ehdoton alaraja låmpotilan sååtelyssa. Se kykeni kohottamaan hapenkulutusta talloin 5-kertaisesti. Lihasvarinan merkitys on vahainen verrattuna kemialliseen låmmontuottoon kylmassa. Tama voitiin osoittaa injisoimalla vasaan sympaattisen hermoston valittajaainetta noradrenaliinia.Temperaturreguleringens utvikling hos nyfødte reinkalver.Abstract in Norwegian / Sammendrag: Temperaturreguleringens utvikling er studert ved å bestemme nyfødte reinkalvers evne til å opprettholde normal kroppstemperatur under påvirkning av gradvis synkende omgivelsestemperatur. Nyfødte kalver (1 døgn gamle kan opprettholde sin kroppstemperatur selv ved -15 °C. De kan øke sin omsetningshastighet fem til seks ganger. I starten er varmeproduksjonen stimulert av det sympatiske nervesystem. Virkningen av tilført noradrenalin og propranolol ble studert og skjelving synes å spille

  17. Changes in the nervous system state and peripheral blood parameters under benzene intoxication during an experiment

    Directory of Open Access Journals (Sweden)

    R.A. Orujov

    2017-12-01

    Full Text Available Benzene is a widely spread chemical health risk factor. Our research goal was to examine the nervous system state and the blood system state under benzene intoxication during an experiment. An acute experiment was performed on 45 white mice with 5-fold poisoning with benzene; a chronic one was performed on 72 rabbits being under inhalation exposure to benzene during 4 months, its concentrations increasing and fluctuating. We determined the following blood parameters: number of reticulocytes, eosinophils, basocytes, and erythrocytes; erythrocytes sedimentation rate; blood clotting period; blood clot retraction; plasma re-calcification period; plasma tolerance to heparin; prothrombin time; prothrombin index; fibrinogen concentration; blood fibrinolytic activity; acetylcholine and choline esterase contents. We also determined adrenalin, noradrenalin, dopamine, and dihydroxyphenylalanine contents in urine. Acute experiments results revealed that one-time exposure to benzene exerted a narcotic effect on the central nervous system which had an excitation phase and inhibition phase. Under a repeat exposure to benzene animals' drug intoxication was shorter. And here neutrophils / leucocytes gradient first increased to 139.5 % from its standards value and then when down under consequent intoxications. We detected relevant changes in morphological picture of animals' peripheral blood and their central and vegetative nervous system under chronic exposure to intermittent and increasing benzene concentrations. So, our research revealed that effects exerted by benzene in small concentrations led to apparent shifts in white blood and catecholamines (adrenalin, noradrenalin, dopamine, and dihydroxyphenylalanine. We also detected certain signs that cate-cholamines endogenous reserves (dihydroxyphenylalanine were depleted and, and also signs of eosinophils-basocytes disso-ciation; such prognostic signs were considered to be unfavorable as it was exactly at that

  18. Biology of post-traumatic stress disorder in childhood and adolescence.

    Science.gov (United States)

    Pervanidou, P

    2008-05-01

    Diverse patterns of cortisol secretion with consistently high circulating catecholamines have been reported in post-traumatic stress disorder (PTSD), an anxiety state that develops after exposure to traumatic life events. Indeed, peripheral cortisol levels have been reported to be low or normal in the majority of adult chronic PTSD studies, whereas, in most paediatric studies, high cortisol values have been documented. Longitudinal studies on PTSD biology, including the transition from childhood to adulthood, may shed light on these discrepancies. In children, elevated evening salivary cortisol in the aftermath of the trauma was predictive of PTSD development 6 months later, whereas plasma interleukin-6 correlated positively with evening cortisol and was equally predictive of later PTSD. Longitudinal assessment of PTSD children 1 and 6 months later revealed progressive normalisation of cortisol levels, whereas noradrenaline concentrations became gradually higher. We hypothesise that, in adults with chronic PTSD, low cortisol levels, together with high catecholamines, may reflect a late event in the natural history of the disorder, months or years after the trauma. The progressive divergence of cortisol and noradrenaline concentrations over time may be responsible for PTSD maintenance in children and explain the differences between the child and adult PTSD endophenotypes. In adults studied immediately after the trauma, and by contrast to children, low cortisol levels are predictive of later PTSD development. Our hypothesis that low cortisol levels may reflect a previous trauma, earlier in development, is supported by the well established observation that prior trauma is a risk factor for a new PTSD diagnosis. The developmental stage of an individual in relation to previous exposure to trauma and PTSD vulnerability are crucial variables that may determine clinical and biological PTSD phenotypes and explain the discrepancies between adults and children in reported

  19. The mysterious trace amines: protean neuromodulators of synaptic transmission in mammalian brain.

    Science.gov (United States)

    Burchett, Scott A; Hicks, T Philip

    2006-08-01

    The trace amines are a structurally related group of amines and their isomers synthesized in mammalian brain and peripheral nervous tissues. They are closely associated metabolically with the dopamine, noradrenaline and serotonin neurotransmitter systems in mammalian brain. Like dopamine, noradrenaline and serotonin the trace amines have been implicated in a vast array of human disorders of affect and cognition. The trace amines are unique as they are present in trace concentrations, exhibit high rates of metabolism and are distributed heterogeneously in mammalian brain. While some are synthesized in their parent amine neurotransmitter systems, there is also evidence to suggest other trace amines may comprise their own independent neurotransmitter systems. A substantial body of evidence suggests that the trace amines may play very significant roles in the coordination of biogenic amine-based synaptic physiology. At high concentrations, they have well-characterized presynaptic "amphetamine-like" effects on catecholamine and indolamine release, reuptake and biosynthesis; at lower concentrations, they possess postsynaptic modulatory effects that potentiate the activity of other neurotransmitters, particularly dopamine and serotonin. The trace amines also possess electrophysiological effects that are in opposition to these neurotransmitters, indicating to some researchers the existence of receptors specific for the trace amines. While binding sites or receptors for a few of the trace amines have been advanced, the absence of cloned receptor protein has impeded significant development of their detailed mechanistic roles in the coordination of catecholamine and indolamine synaptic physiology. The recent discovery and characterization of a family of mammalian G protein-coupled receptors responsive to trace amines such as beta-phenylethylamine, tyramine, and octopamine, including socially ingested psychotropic drugs such as amphetamine, 3,4-methylenedioxymethamphetamine, N

  20. Thermogenic effects of sibutramine and its metabolites

    Science.gov (United States)

    Connoley, Ian P; Liu, Yong-Ling; Frost, Ian; Reckless, Ian P; Heal, David J; Stock, Michael J

    1999-01-01

    The thermogenic activity of the serotonin and noradrenaline reuptake inhibitor sibutramine (BTS 54524; Reductil) was investigated by measuring oxygen consumption (VO2) in rats treated with sibutramine or its two pharmacologically-active metabolites. Sibutramine caused a dose-dependent rise in VO2, with a dose of 10 mg kg−1 of sibutramine or its metabolites producing increases of up to 30% that were sustained for at least 6 h, and accompanied by significant increases (0.5–1.0°C) in body temperature. Based on the accumulation in vivo of radiolabelled 2-deoxy-[3H]-glucose, sibutramine had little or no effect on glucose utilization in most tissues, but caused an 18 fold increase in brown adipose tissue (BAT). Combined high, non-selective doses (20 mg kg−1) of the β-adrenoceptor antagonists, atenolol and ICI 118551, inhibited completely the VO2 response to sibutramine, but the response was unaffected by low, β1-adrenoceptor-selective (atenolol) or β2-adrenoceptor-selective (ICI 118551) doses (1 mg kg−1). The ganglionic blocking agent, chlorisondamine (15 mg kg−1), inhibited completely the VO2 response to the metabolites of sibutramine, but had no effect on the thermogenic response to the β3-adrenoceptor-selective agonist BRL 35135. Similar thermogenic responses were produced by simultaneous injection of nisoxetine and fluoxetine at doses (30 mg kg−1) that had no effect on VO2 when injected individually. It is concluded that stimulation of thermogenesis by sibutramine requires central reuptake inhibition of both serotonin and noradrenaline, resulting in increased efferent sympathetic activation of BAT thermogenesis via β3-adrenoceptor, and that this contributes to the compound's activity as an anti-obesity agent. PMID:10217544

  1. Atomoxetine treatment for nicotine withdrawal: a pilot double-blind, placebo-controlled, fixed-dose study in adult smokers

    Directory of Open Access Journals (Sweden)

    Silverstone Peter H

    2012-03-01

    Full Text Available Abstract Background Many effective treatments for nicotine addiction inhibit noradrenaline reuptake. Three recent studies have suggested that another noradrenaline reuptake inhibitor, atomoxetine, may reduce smoking behaviors. Methods The present double-blind, placebo-controlled, fixed-dose study was carried out over 21 days during which administration of 40 mg atomoxetine was compared to placebo in 17 individuals. Of these, nine were randomized to atomoxetine and eight to placebo. Baseline and weekly measurements were made using the Cigarette Dependence Scale (CDS, Cigarette Withdrawal Scale (CWS, Questionnaire of Smoking Urges (QSU, reported number of cigarettes smoked, and salivary cotinine levels. Results The study results showed that all those on placebo completed the study. In marked contrast, of the nine individuals who started on atomoxetine, five dropped out due to side effects. In a completer analysis there were statistically significant differences at 14 and 21 days in several measures between the atomoxetine and placebo groups, including CDS, CWS, QSU, number of cigarettes smoked (decreasing to less than two per day in the treatment group who completed the study, and a trend towards lower mean salivary cotinine levels. However, these differences were not seen in a last observation carried forward (LOCF analysis. Conclusions In summary, this is the first study to examine the use of atomoxetine in non-psychiatric adult smokers for a period of more than 7 days, and the findings suggest that atomoxetine might be a useful treatment for nicotine addiction. However, the dose used in the current study was too high to be tolerated by many adults, and a dose-finding study is required to determine the most appropriate dose for future studies of this potential treatment for smoking cessation.

  2. Targeting impulsivity in Parkinson’s disease using atomoxetine

    Science.gov (United States)

    Housden, Charlotte R.; Regenthal, Ralf; Barker, Roger A.; Müller, Ulrich; Rowe, James; Sahakian, Barbara J.; Robbins, Trevor W.

    2014-01-01

    Noradrenergic dysfunction may play a significant role in cognition in Parkinson’s disease due to the early degeneration of the locus coeruleus. Converging evidence from patient and animal studies points to the role of noradrenaline in dopaminergically insensitive aspects of the parkinsonian dysexecutive syndrome, yet the direct effects of noradrenergic enhancement have not to date been addressed. Our aim was to directly investigate these, focusing on impulsivity during response inhibition and decision making. To this end, we administered 40 mg atomoxetine, a selective noradrenaline re-uptake inhibitor to 25 patients with Parkinson’s disease (12 female /13 male; 64.4 ± 6.9 years old) in a double blind, randomized, placebo controlled design. Patients completed an extensive battery of neuropsychological tests addressing response inhibition, decision-making, attention, planning and verbal short term memory. Atomoxetine improved stopping accuracy on the Stop Signal Task [F(1,19) = 4.51, P = 0.047] and reduced reflection impulsivity [F(1,9) = 7.86, P = 0.02] and risk taking [F(1,9) = 9.2, P = 0.01] in the context of gambling. The drug also conferred effects on performance as a function of its measured blood plasma concentration: it reduced reflection impulsivity during information sampling [adjusted R2 = 0.23, F(1,16) = 5.83, P = 0.03] and improved problem solving on the One Touch Stockings of Cambridge [adjusted R2 = 0.29, F(1,17) = 8.34, P = 0.01]. It also enhanced target sensitivity during sustained attention [F(1,9) = 5.33, P = 0.046]. The results of this exploratory study represent the basis of specific predictions in future investigations on the effects of atomoxetine in Parkinson’s disease and support the hypothesis that targeting noradrenergic dysfunction may represent a new parallel avenue of therapy in some of the cognitive and behavioural deficits seen in the disorder. PMID:24893708

  3. Pharmacological analysis of the cardiac sympatho-inhibitory actions of moxonidine and agmatine in pithed spontaneously hypertensive rats.

    Science.gov (United States)

    Cobos-Puc, Luis E; Sánchez-López, Araceli; Centurión, David

    2016-11-15

    This study shows that in spontaneously hypertensive rats (SHR) of 14-weeks-old, the sympathetically-induced, but not noradrenaline-induced tachycardic response are higher than age-matched Wistar normotensive rats. Furthermore, in SHR the sympathetically-induced tachycardic response was: (1) unaffected by moxonidine (3μg/kgmin); (2) partially inhibited by B-HT 933 (30μg/kgmin), both at the lowest doses; and (3) completely inhibited by the highest doses of B-HT 933 (100μg/kgmin), moxonidine (10μg/kgmin) or agmatine (1000 and 3000μg/kgmin) while the noradrenaline-induced tachycardic responses remained unaffected by the above compounds, except by 3000μg/kgmin agmatine. In SHR, 300μg/kg rauwolscine failed to block the sympatho-inhibition to 100μg/kgmin B-HT 933 or 10μg/kgmin moxonidine, but 1000μg/kg rauwolscine abolished, partially antagonized, and did not modify the sympatho-inhibition to the highest doses of B-HT 933, moxonidine, and agmatine, respectively, 3000μg/kg AGN 192403 or 300μg/kg BU224 given alone had no effect in the moxonidine- or agmatine-induced sympatho-inhibition, and the combination rauwolscine plus AGN 192403 but not plus BU224, abolished the sympatho-inhibition to the highest doses of moxonidine and agmatine. In conclusion, the sympathetically-induced tachycardic responses in SHR are inhibited by moxonidine and agmatine. The inhibition of moxonidine is mainly mediated by prejunctional α 2 -adrenoceptors and to a lesser extent by I 1 -imidazoline receptors, while the inhibition of agmatine is mediated by prejunctional α 2 -adrenoceptors and I 1 -imidazoline receptors at the same extent. Notwithstanding, the inhibitory function of α 2 -adrenoceptors seems to be altered in SHR compared with Wistar normotensive rats. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Agmatine, an endogenous ligand at imidazoline binding sites, does not antagonize the clonidine-mediated blood pressure reaction

    Science.gov (United States)

    Raasch, Walter; Schäfer, Ulrich; Qadri, Fatimunnisa; Dominiak, Peter

    2002-01-01

    Since agmatine has been identified as a clonidine displacing substance (CDS), the aim of this study was to investigate whether agmatine can mimic CDS-induced cardiovascular reactions in organ bath experiments, pithed spontaneously hypertensive rats (SHR) and anaesthetized SHR.Intravenously-administered agmatine significantly reduced the blood pressure and heart rate of anaesthetized SHR at doses higher than 1 and 3 mg kg−1, respectively. These effects are probably mediated via central mechanisms, since there was an approximate 8 fold rightward shift of the dose-response curve in the pithed SHR (indicating a weakened cardiovascular effect). Moreover, in organ bath experiments, agmatine failed to alter the contractility of intact or endothelium-denuded aortal rings. When agmatine was administered i.c.v. to anaesthetized SHR, blood pressure was increased without any alteration of heart rate, whereas blood pressure was unchanged and heart rate was increased after injection into the 4th brain ventricle. This suggests that haemodynamic reaction patterns after central application are related to distinct influences on central cardiovascular mechanisms.Agmatine reduces noradrenaline release in pithed SHR while α2-adrenoceptors are irreversibly blocked with phenoxybenzamine, but not while I1-binding sites are selectively blocked with AGN192403. This suggests that agmatine may modulate noradrenaline release in the same way that clonidine does, i.e. via imidazoline binding sites; this involves a reduction in sympathetic tone which in turn reduces blood pressure and heart rate.Finally, CDS-like cardiovascular activity appears not to be due to agmatine, since (i) blood pressure in anaesthetized SHR is decreased by agmatine and clonidine, and (ii) agmatine did not antagonize the blood pressure reaction to clonidine in pithed or anaesthetized SHR. PMID:11834614

  5. A search for presynaptic inhibitory histamine receptors in guinea-pig tissues: Further H3 receptors but no evidence for H4 receptors.

    Science.gov (United States)

    Petri, Doris; Schlicker, Eberhard

    2016-07-01

    The histamine H4 receptor is coupled to Gi/o proteins and expressed on inflammatory cells and lymphoid tissues; it was suggested that this receptor also occurs in the brain or on peripheral neurones. Since many Gi/o protein-coupled receptors, including the H3 receptor, serve as presynaptic inhibitory receptors, we studied whether the sympathetic neurones supplying four peripheral tissues and the cholinergic neurones in the hippocampus from the guinea-pig are equipped with release-modulating H4 and H3 receptors. For this purpose, we preincubated tissue pieces from the aorta, atrium, renal cortex and vas deferens with (3)H-noradrenaline and hippocampal slices with (3)H-choline and determined the electrically evoked tritium overflow. The stimulation-evoked overflow in the five superfused tissues was inhibited by the muscarinic receptor agonist oxotremorine, which served as a positive control, but not affected by the H4 receptor agonist 4-methylhistamine. The H3 receptor agonist R-α-methylhistamine inhibited noradrenaline release in the peripheral tissues without affecting acetylcholine release in the hippocampal slices. Thioperamide shifted the concentration-response curve of histamine in the aorta and the renal cortex to the right, yielding apparent pA2 values of 8.0 and 8.1, respectively, which are close to its affinity at other H3 receptors but higher by one log unit than its pKi at the H4 receptor of the guinea-pig. In conclusion, histamine H4 receptors could not be identified in five experimental models of the guinea-pig that are suited for the detection of presynaptic inhibitory receptors whereas H3 receptors could be shown in the peripheral tissues but not in the hippocampus. This article is part of the Special Issue entitled 'Histamine Receptors'. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Beta adrenergic receptors in dog heart characterised in vivo by sup 11 C-CGP 12117 and positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Seto, Mikito [Kanazawa Univ. (Japan). School of Medicine

    1989-06-01

    Beta adrenergic receptors in the dog heart were demonstrated in vivo using a potent antagonist, {sup 11}C-CGP 12117 (Kd=0.2 nmol/kg, in vitro), and positron emission tomography (PET). {sup 11}C-CGP at a high specific radioactivity (approximately 500 Ci/mmol) was intravenously injectd in dogs. Axial transverse slices of the heart were obtained. The concentration of {sup 11}C-CGP 12177 in the myocardium rapidly increased and then remained nearly constant for about 30 minutes, before decreasing slowly. Designing a new method to distinguish specific receptor binding from the total ligand concentration in the heart measured by PET, beta adrenoceptor density in the dog myocardium (Bmax) was found to be 113 pmol/cm{sup 3}. Displacement and pre-saturation studies were performed to demonstrate the specifity of {sup 11}C-CGP 12177 binding for noradrenaline binding sites. The bolus injection of unlabeled CGP 12177 25 min following {sup 11}C-CGP 12177 injection led to a rapid decrease in the myocardial ligand concentration and a rapid fall in the heart rate. Both the pharmacological effect of CGP 12177 and the binding inhibition of radioligand were synchronous with the increasing amount of antagonist injected for displacement. In experiments of presaturation with an excessive dose of unlabeled antagonist injection 10 min before {sup 11}C-CGP 12177 injection, the heart/blood radioligand concentration ratio as a function of time was significantly lower than that in the control study. Thus, specific receptor binding of {sup 11}C-CGP 12177 for noradrenaline binding sites in the living heart was proved by PET, which might be the ideal method to study the physiologically active form of receptors in vivo. (author).

  7. Antidepressant-like effect of rutin isolated from the ethanolic extract from Schinus molle L. in mice: evidence for the involvement of the serotonergic and noradrenergic systems.

    Science.gov (United States)

    Machado, Daniele G; Bettio, Luis E B; Cunha, Mauricio P; Santos, Adair R S; Pizzolatti, Moacir G; Brighente, Inês M C; Rodrigues, Ana Lúcia S

    2008-06-10

    We have recently shown that the hexanic extract from leaves of Schinus molle produces antidepressant-like effects in the tail suspension test in mice. This study investigated the antidepressant-like effect of the ethanolic extract from aerial part of S. molle in the forced swimming test and tail suspension test in mice, two predictive models of depression. Moreover, we investigated the antidepressant potential of rutin, a flavonoid isolated from the ethanolic extract of this plant and the influence of the pretreatment with the inhibitors of serotonin or noradrenaline synthesis, p-chlorophenylalanine methyl ester (PCPA) and alpha-methyl-p-tyrosine (AMPT), respectively in the antidepressant-like effect of this flavonoid. The administration of the ethanolic extract produced a reduction in the immobility time in the tail suspension test (dose range 600-1000 mg/kg, p.o.), but not in the forced swimming test. It also produced a reduction in the ambulation in the open-field test in mice not previously habituated to the arena, but no effect in the locomotor activity in mice previously habituated to the open-field. The administration of rutin reduced the immobility time in the tail suspension test (0.3-3 mg/kg, p.o.), but not in the forced swimming test, without producing alteration in the locomotor activity. In addition, pretreatment of mice with PCPA (100 mg/kg, i.p., for 4 consecutive days) or AMPT (100 mg/kg, i.p.) prevented the anti-immobility effect of rutin (0.3 mg/kg, p.o.) in the tail suspension test. The results firstly indicated the antidepressant-like effect of the ethanolic extract of S. molle in the tail suspension test may be dependent on the presence of rutin that likely exerts its antidepressant-like effect by increasing the availability of serotonin and noradrenaline in the synaptic cleft.

  8. Contrasting Roles of Dopamine and Noradrenaline in the Motivational Properties of Social Play Behavior in Rats

    NARCIS (Netherlands)

    Achterberg, E.J.M.; van Kerkhof, L.W.M.; Servadio, Michela; van Swieten, Maaike; Houwing, Danielle J; Aalderink, Mandy; Driel, Nina V; Trezza, Viviana; Vanderschuren, L.J.M.J.

    2016-01-01

    Social play behavior, abundant in the young of many mammalian species, is generally assumed to be important for social and cognitive development. Social play is highly rewarding, and as such, the expression of social play depends on its pleasurable and motivational properties. Since the motivational

  9. Hypothalamic digoxin, hemispheric dominance, and neurobiology of love and affection.

    Science.gov (United States)

    Kurup, Ravi Kumar; Kurup, Parameswara Achutha

    2003-05-01

    The human hypothalamus produces an endogenous membrane Na+-K+ ATPase inhibitor, digoxin, which can regulate neuronal transmission. The digoxin status and neurotransmitter patterns were studied in individuals with a predilection to fall in love. It was also studied in individuals with differing hemispheric dominance to find out the role of cerebral dominance in this respect. In individuals with a predilection to fall in love there was decreased digoxin synthesis, increased membrane Na+-K+ ATPase activity, decreased tryptophan catabolites (serotonin, quinolinic acid, and nicotine), and increased tyrosine catabolites (dopamine, noradrenaline, and morphine). This pattern correlated with that obtained in left hemispheric chemical dominance. Hemispheric dominance and hypothalamic digoxin could regulate the predisposition to fall in love.

  10. The neuropsychopharmacology of fronto-executive function: monoaminergic modulation.

    Science.gov (United States)

    Robbins, T W; Arnsten, A F T

    2009-01-01

    We review the modulatory effects of the catecholamine neurotransmitters noradrenaline and dopamine on prefrontal cortical function. The effects of pharmacologic manipulations of these systems, sometimes in comparison with the indoleamine serotonin (5-HT), on performance on a variety of tasks that tap working memory, attentional-set formation and shifting, reversal learning, and response inhibition are compared in rodents, nonhuman primates, and humans using, in a behavioral context, several techniques ranging from microiontophoresis and single-cell electrophysiological recording to pharmacologic functional magnetic resonance imaging. Dissociable effects of drugs and neurotoxins affecting these monoamine systems suggest new ways of conceptualizing state-dependent fronto-executive functions, with implications for understanding the molecular genetic basis of mental illness and its treatment.

  11. Effects of Shuyusan on monoamine neurotransmitters expression in a rat model of chronic stress-induced depression

    Institute of Scientific and Technical Information of China (English)

    Yuanyuan Zhang; Jianjun Jia; Liping Chen; Zhitao Han; Yulan Zhao; Honghong Zhang; Yazhuo Hu

    2011-01-01

    Shuyusan, a traditional Chinese medicine, was shown to improve depression symptoms and behavioral scores, as well as increase 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid, and 5-hydroxytryptophan levels, in a rat model of chronic stress-induced depression. However, dopamine, noradrenalin, and 3-methoxy-4-hydroxyphenylglycol expressions remained unchanged following Shuyusan treatment. Compared with the model group, the number of 5-HT-positive neurons in layers 4-5 of the frontal cortex, as well as hippocampal CA1 and CA3 regions, significantly increased following Shuyusan treatment. These results suggested that Shuyusan improved symptoms in a rat model of chronic stress-induced depression with mechanisms that involved 5-HT, 5-HT metabolite, 5-HT precursor expressions.

  12. Adrenergic effects on exocrine secretion of rat submandibular epidermal growth factor

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Nexø, Ebba

    1984-01-01

    The present study was undertaken to investigate the effect of alpha- and beta-adrenergic agonists on secretion of epidermal growth factor (EGF) from the rat submandibular glands and to test the possibility of intestinal absorption of EGF. Alpha-adrenergic agonists increased the concentration...... of salivary EGF by approximately a hundred times, while the serum concentration of EGF was unchanged. The contents of EGF in the submandibular glands decreased upon administration of the alpha-adrenergic agonist noradrenaline, and this was confirmed on immunohistochemical investigation of the glands. Beta-adrenergic....... This study shows that alpha-adrenergic agonists stimulate exocrine secretion of submandibular EGF and that EGF in physiological amounts are not absorbed in the gastrointestinal tract....

  13. 产后抑郁症血浆儿茶酚胺浓度对照研究%The Plasma Catecholamines Control Study of Postnatal Depression

    Institute of Scientific and Technical Information of China (English)

    陆亚文; 吴怀安; 闫小华; 徐宏里; 郑铮; 李英霞

    2003-01-01

    Objective:To explore the plasma catecholamines (CAs) concentration of postnatal depression and to analyze the re-lationships between postnatal depression and CAs level. Methods: Using high performance liquid chromatography (HPLC) to mea-sure the subjects'' plasma noradrenaline (NE)、 adrenaline (E) and dopamine (DA) concentration. The postnatal depression group was compared with depression, ante partum and normal group. Results: NE level of plasma in the depression group and the post-natal depression group were all higher than those of normal group P 0.05) . Conclusion: the plasma NE increase is relative to postnatal depression episode, the plasma DA may be relative to postnatal depression episode. The relationship between plasma and postnatal depression remains unclear.

  14. [Distribution of biogenic amines in the hippocampal formation in the rabbit].

    Science.gov (United States)

    Budantsev, A Iu; Gur'ianova, A D

    1975-06-01

    The hippocampal formation (the hippocampus and the dentate fascia) of the rabbit was studied by histochemical fluorescent method of Falk to determine localization of monoaminergic terminals containing biogenic amines: noradrenalin, dophamine and serotonin. It was shown that monoaminenergic terminals in the hippocampus were in two zones of afferent terminations: in the zone of ending of the perforating way (str. lacunosum-moleculare of fields CA1 and CA2; str. moleculare of the dentate fascia) and in the subgranular zone of the hilum where a part of septofimbrial way terminated on granular neurons of the dentate fascia, the main cellular elements of the hipocampus (pyramidal, granular and basket cells of the hippocampus) did not contain biogenic amines.

  15. The affection of APA microcapsulation on catecholamine and leucine-enkephalin secretion from the bovine adrenal medullary chromaffin cells

    International Nuclear Information System (INIS)

    Guo Shuilong; Cui Xin; Luo Yun; Xue Yilong

    2002-01-01

    The affection of alginate-polylysine-alginate (APA) microcapsulation on catecholamine (CA) and leucine-enkephalin (L-EK) secretion from bovine adrenal medullary chromaffin cells was analysed. Encapsulating BCCs with the APA microcapsulation, the secretion of CA and L-EK in encapsulated BCCs was detected by high-performance liquid chromatography-electrochemical assay and radioimmunoassay, respectively. There is little difference between the encapsulated BCCs and the non-encapsulated BCCs in the secretion of epinephrine (E) and noradrenaline (NE) but the secretion of dopamine (DA) and L-EK in several points decline. The studies indicated that APA microcapsulation of BCCs didn't affect the secretion of E and NE, but did the secretion DA and L-EK in forepart

  16. Sibutramine reduces feeding, body fat and improves insulin resistance in dietary-obese male Wistar rats independently of hypothalamic neuropeptide Y

    Science.gov (United States)

    Brown, Michael; Bing, Chen; King, Peter; Pickavance, Lucy; Heal, David; Wilding, John

    2001-01-01

    We studied the effects of the novel noradrenaline and serotonin (5-HT) reuptake inhibitor sibutramine on feeding and body weight in a rat model of dietary obesity, and whether it interacts with hypothalamic neuropeptide Y (NPY) neurones.Chow-fed and dietary-obese (DIO) male Wistar rats were given sibutramine (3 mg kg−1 day−1 p.o.) or deionized water for 21 days.Sibutramine decreased food intake throughout the treatment period in both dietary-obese rats (Psibutramine-treated dietary-obese rats (Psibutramine treatment (Psibutramine compared to untreated controls.The hypophagic and anti-obesity effects of sibutramine in dietary-obese Wistar rats appear not to be mediated by inhibition of ARC NPY neurones. PMID:11309262

  17. KERDO INFORMATIVE INDEX TO DETERMINE THE LEVEL OF VIOLATIONS OF AUTONOMIC REGULATION AT OSTEOCHONDROSIS OF THE CERVICAL S PINE

    Directory of Open Access Journals (Sweden)

    V. P. Martsenyuk

    2013-05-01

    Full Text Available This paper evaluated t he informative value of the index Kerdo in patients with і mpaired autonomic regulation at osteochondrosis of the cervical spine. The calculated value of the information in these reports: the content of adrenaline and noradrenaline in daily urine acetylcholinesterase activity in capillary blood, systolic, diastolic pressure and heart rate in patients with neurological syndromes of degenerative disc disease of the cervical spine. They were more than the value of information in the index Kerdo with relevant pathology. We could not find sufficient information of Kerdo index to determine the level and direction of disorders of autonomic regulation in patients with neurological syndromes of osteochondrosis of the cervical spine.

  18. Conditioned pain modulation: a predictor for development and treatment of neuropathic pain.

    Science.gov (United States)

    Granovsky, Yelena

    2013-09-01

    Psychophysical evaluation of endogenous pain inhibition via conditioned pain modulation (CPM) represents a new generation of laboratory tests for pain assessment. In this review we discuss recent findings on CPM in neuropathic pain and refer to psychophysical, neurophysiological, and methodological aspects of its clinical implications. Typically, chronic neuropathic pain patients express less efficient CPM, to the extent that incidence of acquiring neuropathic pain (e.g. post-surgery) and its intensity can be predicted by a pre-surgery CPM assessment. Moreover, pre-treatment CPM evaluation may assist in the correct choice of serotonin-noradrenalin reuptake inhibitor analgesic agents for individual patients. Evaluation of pain modulation capabilities can serve as a step forward in individualizing pain medicine.

  19. Calorigenic effect of adrenaline in rats under conditions of restricted motor activity

    Science.gov (United States)

    Tomaszewska, L.; Kaciuba-Uscilko, H.; Kozlowski, S.

    1980-01-01

    In previous studies, it was demonstrated that long term restricted motor activity in rats induces a decrease in body weight, an increase in release of adrenaline, and a decrease in the release of noradrenaline with the urine, as well as a reduction in activity of the thymus gland and level of thyroxin in the blood. At the same time, a decrease was found in the internal body temperature that was accompanied by an increase in the rate of metabolism in the state of rest. An investigation is presented which attempts to clarify whether the calorigenic effect of adrenaline under conditions of increased metabolism in the period of immobility is exposed to changes.

  20. High Circulating Adrenaline Levels at Admission Predict Increased Mortality After Trauma

    DEFF Research Database (Denmark)

    Johansson, Pär Ingemar; Stensballe, Jakob; Rasmussen, Lars Simon

    2012-01-01

    partial thromboplastin time, international normalized ratio, hematology, biochemistry, circulating adrenaline and noradrenaline, 11 biomarkers of tissue and endothelial damage, glycocalyx degradation, natural anticoagulation and fibrinolysis (histone-complexed DNA fragments, high-mobility group box 1......:: The adrenaline level was increased in nonsurvivors (p = 0.026), it was independently associated with increased activated partial thromboplastin time (p = 0.034) and syndecan-1 (p = 0.007), a marker of glycocalyx degradation, and it correlated with biomarkers of tissue and endothelial damage (histone......-complexed DNA, high-mobility group box 1, soluble thrombomodulin) and hyperfibrinolysis (tissue-type plasminogen activator, d-dimer). Furthermore, nonsurvivors had higher syndecan-1, tissue factor pathway inhibitor, and d-dimer levels (all p adrenaline was independently associated with 30...