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Sample records for gene-related peptide nitric

  1. Forearm vascular response to nitric oxide and calcitonin gene-related peptide: comparison between migraine patients and control subjects.

    NARCIS (Netherlands)

    Hoon, J.N. de; Smits, P.; Troost, J.; Struijker-Boudier, H.A.; Bortel, L.M. van

    2006-01-01

    The forearm vascular response to nitric oxide (NO) and calcitonin gene-related peptide (CGRP) was investigated in 10 migraine patients and 10 matched control subjects. Changes in forearm blood flow (FBF) during intrabrachial infusion of: (i) serotonin (releasing endogenous NO), (ii) sodium nitroprus

  2. Neuronal nitric oxide synthase immunoreactivity in the guinea-pig liver: distribution and colocalization with neuropeptide Y and calcitonin gene-related peptide.

    Science.gov (United States)

    Esteban, F J; Jiménez, A; Fernández, A P; del Moral, M L; Sánchez-López, A M; Hernández, R; Garrosa, M; Pedrosa, J A; Rodrigo, J; Peinado, M A

    2001-12-01

    The innervation pattern of the guinea-pig liver is similar to that of the human liver. However, many aspects of the distribution of the neuronal isoform of the enzyme nitric oxide synthase (nNOS) in the guinea-pig liver and its colocalization with neuropeptides remain to be elucidated. The distribution of nNOS was studied in fixed guinea-pig liver by light microscopic immunohistochemistry. Confocal analysis was used to determine its colocalization with neuropeptide Y (NPY) or calcitonin gene-related peptide (CGRP). nNOS-immunoreactive (nNOS-IR) nerves were observed in relation to hilar and interlobar vessels and in Glisson's capsule. A few nNOS-IR ganglia were observed in the extrahepatic bile duct and close to the interlobar portal triads. In addition, nNOS-IR fibers were located in the interlobular portal triads and pervading the parenchyma. Moreover, nNOS-IR nerves were demonstrated for the first time in the larger central veins and in the hepatic vein. nNOS-NPY and nNOS-CGRP colocalizations were detected in the fibromuscular layer of the bile duct and periductal plexus, respectively. These results support the phylogenetic conservation of the nNOS-IR hepatic innervation and its possible contribution to the regulation of hepatic blood flow and certain hepatic functions.

  3. Calcitonin gene related peptide and its functions

    Directory of Open Access Journals (Sweden)

    Karimian M

    1998-07-01

    Full Text Available Calcitonin Gene Related Peptide (CGRP was first reported in 1982. This peptide contains 37 amino acids which could be found in Alpha and Beta forms. CGRP shows diversity both in its receptors and biological effects and up to now four different types of receptors have been reported. It can act like a neurotransmitter, local hormone and neuromodulator. They have a variety of effects on different organs such as a potent effect on vasodilation and smooth muscle relaxation. Ability of CGRP for induction of protein extravasation from blood vessels was uncertain. In this study intra-articular infusion of 10^-6 M CGRP to the rat knee joint induced significant protein extravasation into the rat knee joint space. The amount of protein was detected by modified Iawata method which could detect amount of protein between 5-500 mg/L. Higher and lower concentrations failed to induce protein extravasation. Failure in higher concentration was likely due to significant fall in blood pressure. In the presence of an arterial hypotension induced by an ? adenoreceptor antagonist, 10^-6 M of CGRP failed to produce protein extravasation. This effect of CGRP was a specific active effect and not a passive effect due to its potent vasodilation effect, as similar vasodilatory response induced by a ?-adrenoreceptor agonist failed to induce protein extravasation. There is more than 50% of sensory neurons which contain CGRP and they are spread in all over the body and joints, therefore CGRP induced protein extravasation can potentiate inflammation in different organs.

  4. Nitric oxide synthase, calcitonin gene-related peptide and NK-1 receptor mechanisms are involved in GTN-induced neuronal activation

    DEFF Research Database (Denmark)

    Ramachandran, Roshni; Bhatt, Deepak Kumar; Ploug, Kenneth Beri

    2014-01-01

    -related peptide (CGRP) systems on the GTN-induced neuronal activation in this model. MATERIALS AND METHODS: The femoral vein was catheterised in rats and GTN was infused (4 µg/kg/min, for 20 minutes, intravenously). Immunohistochemistry was performed to analyse Fos, nNOS and CGRP and Western blot for measuring n...

  5. Calcitonin Gene-Related Peptide (CGRP in Cerebrovascular Disease

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    Lars Edvinsson

    2002-01-01

    Full Text Available Cerebral blood vessels are innervated by sensory nerves that store several neurotransmitters among which calcitonin gene-related peptide (CGRP is the most abundant. In primary headaches, there is a clear association between the head pain and the release of CGRP. In cluster headache there is an additional release of vasoactive intestinal peptide (VIP.

  6. Calcitonin gene-related peptide, neurokinin A and substance P

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U; Nielsen, L B; Jensen, Kai

    1991-01-01

    Calcitonin gene-related peptide (CGRP) was injected alone and in combination with substance P (SP) or neurokinin A (NKA) into the forearm skin and temporal muscle of human volunteers. In the skin, 50 pmol of CGRP induced a wheal response and a delayed erythema. No pain was recorded. No interaction...

  7. Calcitonin gene-related peptide and migraine with aura

    DEFF Research Database (Denmark)

    Hansen, Jakob M; Ashina, Messoud

    2014-01-01

    BACKGROUND: Calcitonin gene-related peptide (CGRP) is a key molecule in migraine pathophysiology. Most studies have focused on CGRP in relation to migraine without aura (MO). About one-third of migraine patients have attacks with aura (MA), and this is a systematic review of the current literature...... on CGRP and MA. METHODS: We performed a systematic literature search on MEDLINE for reports of CGRP and MA, covering basic science, animal and human studies as well as randomized clinical trials. RESULTS: The literature search identified 594 citations, of which 38 contained relevant, original data. Plasma...

  8. Calcitonin gene-related peptide in cervicogenic headache

    DEFF Research Database (Denmark)

    Frese, Amalie; Schilgen, M; Edvinsson, L

    2005-01-01

    Trigeminovascular activation is involved in the pathophysiology of migraine and cluster headache. The marker evaluated best for trigeminovascular activation is calcitonin gene-related peptide (CGRP) in the cranial circulation. It is unknown whether trigeminovascular activation plays any role...... in cervicogenic headache (CEH). The objective of this study was to investigate CGRP plasma levels in CEH patients in relation to headache state. To compare plasma CGRP levels between the peripheral and the cranial circulation. Blood from both external jugular veins and from the antecubital vein was drawn from 11...... patients with CEH. Plasma CGRP levels were measured by radioimmunoassay. No difference was found between CGRP levels assessed on days with and without headache. There was no difference between CGRP levels from the symptomatic and the asymptomatic external jugular vein and the antecubital vein...

  9. Involvement of calcitonin gene-related peptide in migraine

    DEFF Research Database (Denmark)

    Lassen, L H; Jacobsen, V B; Haderslev, P A

    2008-01-01

    mug/min) or placebo for 20 min was studied in 12 patients with migraine without aura outside attacks. Xenon-133 inhalation SPECT-determined regional cerebral blood flow (rCBF) and transcranial Doppler (TCD)-determined blood velocity (V (mean)) in the middle cerebral artery (MCA), as well as the heart......Calcitonin gene-related peptide (CGRP)-containing nerves are closely associated with cranial blood vessels. CGRP is the most potent vasodilator known in isolated cerebral blood vessels. CGRP can induce migraine attacks, and two selective CGRP receptor antagonists are effective in the treatment...... of migraine attacks. It is therefore important to investigate its mechanism of action in patients with migraine. We here investigate the effects of intravenous human alpha-CGRP (halphaCGRP) on intracranial hemodynamics. In a double-blind, cross-over study, the effect of intravenous infusion of halphaCGRP (2...

  10. Calcitonin gene-related peptide and adrenomedullin release in humans

    DEFF Research Database (Denmark)

    Hasbak, Philip; Lundby, Carsten; Olsen, Niels Vidiendal

    2002-01-01

    ). Plasma values of CGRP, AM, calcitonin, noradrenaline, adrenaline, lactate and heart rate were measured at rest and during maximal exercise (W(max)). On each study day, the dopamine D(2)-receptor antagonist, domperidone (30 mg; n=6), or no medication (n=6) was given 1 h before exercise. W(max) at SL, HA1......Calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) are potent vasorelaxant peptides. This study examined exercise-induced changes in CGRP and AM levels in 12 healthy sea level natives at sea level (SL) and subsequently after 24 h (HA1) and 5 days (HA5) in high altitude hypoxia (4559 m...... and HA5 increased CGRP and AM along with heart rate, lactate and catecholamines, whereas, calcitonin remained unchanged. The maximal CGRP levels at W(max) were significantly decreased at HA1 (74.3+/-6.1 pmol/l; p=0.002) and HA5 (69.6+/-6.0 pmol/l; p...

  11. Calcitonin Gene-Related Peptide in Tension-Type Headache

    Directory of Open Access Journals (Sweden)

    M. Ashina

    2002-01-01

    Full Text Available In the last 10 years there has been increasing interest in the role of calcitonin gene-related peptide (CGRP in primary headaches. Tension-type headache is one of the most common and important types of primary headaches, and ongoing nociception from myofascial tissues may play an important role in the pathophysiology of this disorder. CGRP sensory fibers are preferentially located in the walls of arteries, and nerve fibers containing CGRP accompany small blood vessels in human cranial muscles. It is well established that nociception may lead to release of CGRP from sensory nerve endings and from central terminals of sensory afferents into the spinal cord. It has also been shown that density of CGRP fibers around arteries is increased in persistently inflamed muscle. These findings indicate that ongoing activity in sensory neurons in the cranial muscles may be reflected in changes of plasma levels of neuropeptides in patients with chronic tension-type headache. To explore the possible role of CGRP in tension-type headache, plasma levels of CGRP were measured in patients with chronic tension-type headache. This study showed that plasma levels of CGRP are normal in patients and unrelated to headache state. However, the findings of normal plasma levels of CGRP do not exclude the possibility that abnormalities of this neuropeptide at the neuronal or peripheral (pericranial muscles levels play a role in the pathophysiology of tension-type headache. Investigation of CGRP in other compartments with new sensitive methods of analysis is necessary to clarify its role in tension-type headache.

  12. Quantitative Structure-Activity Relationships and Docking Studies of Calcitonin Gene-Related Peptide Antagonists

    DEFF Research Database (Denmark)

    Jenssen, Håvard; Mehrabian, Mohadeseh; Kyani, Anahita

    2012-01-01

    resulted in an extremely robust and highly predictive model with calibration, leave-one-out and leave-20-out validation R 2 of 0.9194, 0.9103, and 0.9214, respectively. We performed docking of the most potent calcitonin gene-related peptide antagonists with the calcitonin gene-related peptide receptor...

  13. Activities of calcitonin gene-related peptide (CGRP) and related peptides at the CGRP receptor

    Energy Technology Data Exchange (ETDEWEB)

    Maton, P.N.; Pradhan, T.; Zhou, Z.C.; Gardner, J.D.; Jensen, R.T. (National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD (USA))

    1990-05-01

    In guinea pig pancreatic acini rat calcitonin gene-related peptide (CGRP) increased amylase release 2-fold, salmon calcitonin had an efficacy of only 44% of that of CGRP and (Tyr0)CGRP(28-37) and human calcitonin had no actions. (Tyr0)CGRP(28-37), but not human calcitonin, antagonized the actions of CGRP in pancreatic acini with an IC50 of 3 microM. (Tyr0)CGRP(28-37) produced a parallel rightward shift in the dose-response curve for CGRP-stimulated amylase secretion. The inhibition was specific for CGRP and was reversible. Studies with 125I-CGRP demonstrated that CGRP, salmon calcitonin and (Tyr0)CGRP, but not human calcitonin, interacted with CGRP receptors on pancreatic acini. These results indicate that various CGRP-related peptides demonstrate different relationships between their abilities to occupy the CGRP receptor and to affect biologic activity, with CGRP itself being a full agonist, salmon calcitonin a partial agonist, (Tyr0)CGRP(28-37) a competitive antagonist, and human calcitonin having no actions.

  14. Serotonin, calcitonin and calcitonin gene-related peptide in acute pancreatitis

    DEFF Research Database (Denmark)

    Wahlstrøm, Kirsten Lykke; Novovic, Srdan; Ersbøll, Annette Kjær

    2017-01-01

    OBJECTIVE: The aim of this study was to investigate plasma levels of serotonin, calcitonin and calcitonin gene-related peptide (CGRP) in the course of acute pancreatitis (AP) taking organ failure, etiology and severity into consideration. MATERIAL AND METHODS: Sixty consecutive patients with alco......OBJECTIVE: The aim of this study was to investigate plasma levels of serotonin, calcitonin and calcitonin gene-related peptide (CGRP) in the course of acute pancreatitis (AP) taking organ failure, etiology and severity into consideration. MATERIAL AND METHODS: Sixty consecutive patients...... dysfunction. We hypothesize that serotonin plays a pathogenic role in the compromised pancreatic microcirculation, and calcitonin a role as a biomarker of severity in AP....

  15. Calcitonin gene-related peptide does not cause migraine attacks in patients with familial hemiplegic migraine

    DEFF Research Database (Denmark)

    Hansen, Jakob M; Thomsen, Lise L; Olesen, Jes

    2011-01-01

    Calcitonin gene-related peptide (CGRP) is a key molecule in migraine pathogenesis. Intravenous CGRP triggers migraine-like attacks in patients with migraine with aura and without aura. In contrast, patients with familial hemiplegic migraine (FHM) with known mutations did not report more migraine-...

  16. Effect of the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant in human cranial arteries

    NARCIS (Netherlands)

    L. Edvinsson (Lars); K.Y. Chan (Kayi); S. Eftekhari; E. Nilsson (Elisabeth); R. de Vries (René); H. Säveland (Hans); C.M.F. Dirven (Clemens); A.H.J. Danser (Jan)

    2010-01-01

    textabstractIntroduction: Calcitonin gene-related peptide (CGRP) is a neuronal messenger in intracranial sensory nerves and is considered to play a significant role in migraine pathophysiology. Materials and methods: We investigated the effect of the CGRP receptor antagonist, telcagepant, on CGRP-in

  17. Calcitonin gene-related peptide does not cause the familial hemiplegic migraine phenotype

    DEFF Research Database (Denmark)

    Hansen, J.M.; Thomsen, L.L.; Olesen, J.

    2008-01-01

    Objective: The neuropeptide calcitonin gene-related peptide (CGRP) is a migraine trigger that plays a crucial role in migraine pathophysiology, and CGRP antagonism is efficient in the treatment of migraine attacks. Familial hemiplegic migraine (FHM) is a dominantly inherited subtype of migraine.......58). Headache severity and intensity were not different between the groups. Conclusions: Familial hemiplegic migraine ( FHM) patients do not show hypersensitivity of the calcitonin gene-related peptide (CGRP)-cyclic adenosine 3 ', 5 '-monophosphate pathway, as characteristically seen in migraine patients...... with aura associated with several gene mutations. FHM shares many phenotypical similarities with common types of migraine, indicating common neurobiological pathways. We tested the hypothesis that the FHM genotype confers a CGRP hypersensitive phenotype. Methods: We included 9 FHM patients with known...

  18. Calcitonin gene-related peptide does not cause migraine attacks in patients with familial hemiplegic migraine

    DEFF Research Database (Denmark)

    Hansen, Jakob M; Thomsen, Lise L; Olesen, Jes

    2011-01-01

    Calcitonin gene-related peptide (CGRP) is a key molecule in migraine pathogenesis. Intravenous CGRP triggers migraine-like attacks in patients with migraine with aura and without aura. In contrast, patients with familial hemiplegic migraine (FHM) with known mutations did not report more migraine......-like attacks compared to controls. Whether CGRP triggers migraine-like attacks in FHM patients without known mutations is unknown....

  19. Calcitonin gene-related peptide (CGRP) levels during glyceryl trinitrate (GTN)-induced headache in healthy volunteers.

    Science.gov (United States)

    Kruuse, C; Iversen, H K; Jansen-Olesen, I; Edvinsson, L; Olesen, J

    2010-04-01

    The role of nitric oxide (NO) in migraine has been studied in the experimental glyceryl trinitrate (GTN)-infusion headache model. We hypothesized that GTN-induced headache may activate the trigeminovascular system and be associated with increased levels of sensory neuropeptides, including calcitonin gene-related peptide (CGRP). CGRP, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and somatostatin plasma levels were measured before and after placebo/sumatriptan injection and during GTN-induced headache. Following a double-blind randomized cross-over design, 10 healthy volunteers received subcutaneous sumatriptan 6 mg or placebo. This was succeeded by 20 min of GTN (0.12 µg kg(-1) min(-1)) infusion. At baseline no subject reported headache (using verbal rating scale from 0 to 10) and the jugular CGRP-like immunoreactivity (-LI) level was 18.6 ± 2.5 pmol/l. After a 20-min intravenous infusion of GTN 0.12 µg kg(-1) min(-1), median peak headache intensity was 4 (range 2-6) (P 0.05). There were no changes in VIP-, NPY- or somatostatin-LI. In conclusion, the NO donor GTN appears not to induce headache via immediate CGRP release.

  20. The role of calcitonin gene-related peptide in peripheral and central pain mechanisms including migraine.

    Science.gov (United States)

    Iyengar, Smriti; Ossipov, Michael H; Johnson, Kirk W

    2017-04-01

    Calcitonin gene-related peptide (CGRP) is a 37-amino acid peptide found primarily in the C and Aδ sensory fibers arising from the dorsal root and trigeminal ganglia, as well as the central nervous system. Calcitonin gene-related peptide was found to play important roles in cardiovascular, digestive, and sensory functions. Although the vasodilatory properties of CGRP are well documented, its somatosensory function regarding modulation of neuronal sensitization and of enhanced pain has received considerable attention recently. Growing evidence indicates that CGRP plays a key role in the development of peripheral sensitization and the associated enhanced pain. Calcitonin gene-related peptide is implicated in the development of neurogenic inflammation and it is upregulated in conditions of inflammatory and neuropathic pain. It is most likely that CGRP facilitates nociceptive transmission and contributes to the development and maintenance of a sensitized, hyperresponsive state not only of the primary afferent sensory neurons but also of the second-order pain transmission neurons within the central nervous system, thus contributing to central sensitization as well. The maintenance of a sensitized neuronal condition is believed to be an important factor underlying migraine. Recent successful clinical studies have shown that blocking the function of CGRP can alleviate migraine. However, the mechanisms through which CGRP may contribute to migraine are still not fully understood. We reviewed the role of CGRP in primary afferents, the dorsal root ganglion, and in the trigeminal system as well as its role in peripheral and central sensitization and its potential contribution to pain processing and to migraine.

  1. Calcitonin gene-related peptide induced migraine attacks in patients with and without familial aggregation of migraine

    DEFF Research Database (Denmark)

    Guo, Song; Christensen, Anne Francke; Liu, Marie Louise

    2017-01-01

    BACKGROUND: Calcitonin gene-related peptide provokes migraine attacks in 65% of patients with migraine without aura. Whether aggregation of migraine in first-degree relatives (family load) or a high number of risk-conferring single nucleotide polymorphisms contributes to migraine susceptibility...... to calcitonin gene-related peptide infusion in migraine patients is unknown. We hypothesized that genetic enrichment plays a role in triggering of migraine and, therefore, migraine without aura patients with high family load would report more migraine attacks after calcitonin gene-related peptide infusion than...... patients with low family load. METHODS: We allocated 40 previously genotyped migraine without aura patients to receive intravenous infusion of 1.5 µg/min calcitonin gene-related peptide and recorded migraine attacks including headache characteristics and associated symptoms. Information of familial...

  2. Calcitonin gene-related peptide targeted immunotherapy for migraine: progress and challenges in treating headache.

    Science.gov (United States)

    Peroutka, Stephen J

    2014-06-01

    A role for calcitonin gene-related peptide (CGRP) in the pathophysiology of migraine has been established over the past 25 years. There have now been at least five different small-molecule CGRP antagonists that have demonstrated statistical proof of efficacy in the acute treatment of migraine. At present, multiple clinical trials are underway that are assessing the ability of long-acting antibodies against CGRP to prevent frequent migraine attacks. This review summarizes the existing data concerning the role of CGRP in migraine and attempts to highlight some possible outcomes from the ongoing anti-CGRP antibody trials.

  3. Differential localization and characterization of functional calcitonin gene-related peptide receptors in human subcutaneous arteries

    DEFF Research Database (Denmark)

    Edvinsson, L; Ahnstedt, H; Larsen, R;

    2014-01-01

    Calcitonin gene-related peptide (CGRP) and its receptor are widely distributed within the circulation and the mechanism behind its vasodilation not only differs from one animal species to another but is also dependent on the type and size of vessel. The present study examines the nature of CGRP......-induced vasodilation, characteristics of the CGRP receptor antagonist telcagepant and localization of the key components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) of the CGRP receptor in human subcutaneous arteries....

  4. Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura

    DEFF Research Database (Denmark)

    Hansen, Jakob Møller; Hauge, Anne Werner; Olesen, J.

    2010-01-01

    Calcitonin gene-related peptide (CGRP) is a key molecule in migraine pathogenesis. Intravenous CGRP infusion triggers delayed migraine-like attacks in patients with migraine without aura (MO). In contrast to patients with MO, in prior studies patients with familial hemiplegic migraine (FHM) did...... not report more migraine-like attacks compared to controls. Whether CGRP triggers migraine in patients with typical (non-hemiplegic) migraine with aura is (MA) unknown. In the present study we examined the migraine inducing effect of CGRP infusion in patients suffering from MA and healthy controls....

  5. Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura

    DEFF Research Database (Denmark)

    Hansen, Jakob Møller; Hauge, Anne Werner; Olesen, Jes

    2010-01-01

    Calcitonin gene-related peptide (CGRP) is a key molecule in migraine pathogenesis. Intravenous CGRP infusion triggers delayed migraine-like attacks in patients with migraine without aura (MO). In contrast to patients with MO, in prior studies patients with familial hemiplegic migraine (FHM) did...... not report more migraine-like attacks compared to controls. Whether CGRP triggers migraine in patients with typical (non-hemiplegic) migraine with aura is (MA) unknown. In the present study we examined the migraine inducing effect of CGRP infusion in patients suffering from MA and healthy controls....

  6. Calcitonin gene-related peptide (CGRP) in the nipple of the rat mammary gland

    DEFF Research Database (Denmark)

    Thulesen, J; Rasmussen, T N; Schmidt, P;

    1994-01-01

    The distribution of nerve fibres immunoreactive to calcitonin gene-related peptide (CGRP) was investigated by immunohistochemistry in nipples and mammary glands from lactating and non-lactating rats and compared to the immunoreactivity of other neuropeptides including substance P (SP), neuropeptide...... Y (NPY), vasoactive intestinal peptide (VIP) and somatostatin (SOM). The study revealed an extensive innervation of the mammary nipples, in which CGRP-immunoreactive (IR) nerve fibres were abundantly present in the epidermis, dermal connective tissue and intralobular connective tissue of the mammary...... gland parenchyma. Several of the dermal CGRP-IR fibres seemed to follow blood vessels, or formed "ringlet-like" structures. The latter were mostly observed in the dermal connective tissue of the nipple from the lactating rat and may have a mechanoreceptive function, e.g. for the suckling stimuli...

  7. No increase of calcitonin gene-related peptide in jugular blood during migraine

    DEFF Research Database (Denmark)

    Tvedskov, Jesper; Lipka, Kerstin; Ashina, Messoud

    2005-01-01

    Increased calcitonin gene-related peptide (CGRP) in external jugular venous blood during migraine attack is one of the most cited findings in the headache literature. The finding has not been convincingly reproduced and is based on comparison with historic control subjects. The validity of this f......Increased calcitonin gene-related peptide (CGRP) in external jugular venous blood during migraine attack is one of the most cited findings in the headache literature. The finding has not been convincingly reproduced and is based on comparison with historic control subjects. The validity...... in 17 patients, whereas only cubital fossa blood could be sampled in an additional 4 patients. CGRP was measured with the same assay as most previous studies (assay I) and furthermore with a more sensitive and validated assay (assay II). For assay I, mean CGRP concentration in external jugular venous...... blood during attack was 17.18 pmol/L compared with 15.88 pmol/L outside of attack. Mean difference was 1.81 pmol/L (95% confidence interval [CI]: -2.88, 6.41; p = 0.44). In peripheral blood during attack, CGRP was 16.86 pmol/L compared with 17.57 pmol/L outside of attack. Mean difference was -0.79 pmol...

  8. Role of calcitonin gene-related peptide in cerebral vasospasm, and as a therapeutic approach to subarachnoid haemorrhage

    Directory of Open Access Journals (Sweden)

    Stelios eKokkoris

    2012-11-01

    Full Text Available Calcitonin gene-related peptide (CGRP is one of the most potent microvascular vasodilators identified to date. Vascular relaxation and vasodilation is mediated via activation of the CGRP receptor. This atypical receptor is made up of a G-protein-coupled receptor called calcitonin receptor-like receptor (CLR, a single transmembrane protein called receptor activity-modifying protein (RAMP, and an additional protein that is required for Gas coupling, known as receptor component protein (RCP. Several mechanisms involved in CGRP mediated relaxation have been identified. These include nitric oxide (NO-dependent endothelium-dependent mechanisms or cAMP-mediated endothelium-independent pathways; the latter being more common. Subarachnoid haemorrhage (SAH is associated with cerebral vasoconstriction that occurs several days after the haemorrhage and is often fatal. The vasospasm occurs in 30–40% of patients and is the major cause of death from this condition. The vasoconstriction is associated with a decrease in CGRP levels in nerves and an increase in CGRP levels in draining blood, suggesting that CGRP is released from nerves to oppose the vasoconstriction. This evidence has led to the concept that exogenous CGRP may be beneficial in a condition that has proven hard to treat. The present article reviews: a the pathophysiology of delayed ischaemic neurologic deficit after SAH b the basics of the CGRP receptor structure, signal transduction and vasodilatation mechanisms and c the studies that have been conducted so far using CGRP in both animals and humans with SAH.

  9. Occurrence of substance P, vasoactive intestinal peptide, and calcitonin gene-related peptide in dermographism and cold urticaria.

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    Wallengren, J; Möller, H; Ekman, R

    1987-01-01

    Substance P (SP), calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP) were assayed in lesions and normal skin of patients with dermographism and cold urticaria utilizing suction-induced blisters. There was no difference in SP and VIP concentrations between challenged and control skin of urticaria patients. On the whole, however, the concentration of both neuropeptides, and VIP in particular, was higher in the urticaria patients than in control subjects. CGRP levels were not increased. SP and VIP in blood samples from veins draining challenged skin areas were below the detection limit. It is concluded that SP and VIP may potentiate histamine in wheal formation and thus contribute to the increased reactivity of the skin to trauma and temperature changes in patients with physical urticaria.

  10. Calcitonin gene-related peptide (CGRP) levels during glyceryl trinitrate (GTN)-induced headache in healthy volunteers

    DEFF Research Database (Denmark)

    Kruuse, C; Iversen, Helle Klingenberg; Jansen-Olesen, I

    2010-01-01

    calcitonin gene-related peptide (CGRP). CGRP, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and somatostatin plasma levels were measured before and after placebo/sumatriptan injection and during GTN-induced headache. Following a double-blind randomized cross-over design, 10 healthy volunteers...

  11. Heat hyperalgesia and mechanical hypersensitivity induced by calcitonin gene-related peptide in a mouse model of neurofibromatosis.

    Directory of Open Access Journals (Sweden)

    Stephanie White

    Full Text Available This study examined whether mice with a deficiency of neurofibromin, a Ras GTPase activating protein, exhibit a nociceptive phenotype and probed a possible contribution by calcitonin gene-related peptide. In the absence of inflammation, Nf1+/- mice (B6.129S6 Nf1/J and wild type littermates responded comparably to heat or mechanical stimuli, except for a subtle enhanced mechanical sensitivity in female Nf1+/- mice. Nociceptive phenotype was also examined after inflammation induced by capsaicin and formalin, which release endogenous calcitonin gene-related peptide. Intraplantar injection of capsaicin evoked comparable heat hyperalgesia and mechanical hypersensitivity in Nf1+/- and wild type mice of both genders. Formalin injection caused a similar duration of licking in male Nf1+/- and wild type mice. Female Nf1+/- mice licked less than wild type mice, but displayed other nociceptive behaviors. In contrast, intraplantar injection of CGRP caused greater heat hyperalgesia in Nf1+/- mice of both genders compared to wild type mice. Male Nf1+/- mice also exhibited greater mechanical hypersensitivity; however, female Nf1+/- mice exhibited less mechanical hypersensitivity than their wild type littermates. Transcripts for calcitonin gene-related peptide were similar in the dorsal root ganglia of both genotypes and genders. Transcripts for receptor activity-modifying protein-1, which is rate-limiting for the calcitonin gene-related peptide receptor, in the spinal cord were comparable for both genotypes and genders. The increased responsiveness to intraplantar calcitonin gene-related peptide suggests that the peripheral actions of calcitonin gene-related peptide are enhanced as a result of the neurofibromin deficit. The analgesic efficacy of calcitonin gene-related peptide receptor antagonists may therefore merit investigation in neurofibromatosis patients.

  12. Heat hyperalgesia and mechanical hypersensitivity induced by calcitonin gene-related peptide in a mouse model of neurofibromatosis.

    Science.gov (United States)

    White, Stephanie; Marquez de Prado, Blanca; Russo, Andrew F; Hammond, Donna L

    2014-01-01

    This study examined whether mice with a deficiency of neurofibromin, a Ras GTPase activating protein, exhibit a nociceptive phenotype and probed a possible contribution by calcitonin gene-related peptide. In the absence of inflammation, Nf1+/- mice (B6.129S6 Nf1/J) and wild type littermates responded comparably to heat or mechanical stimuli, except for a subtle enhanced mechanical sensitivity in female Nf1+/- mice. Nociceptive phenotype was also examined after inflammation induced by capsaicin and formalin, which release endogenous calcitonin gene-related peptide. Intraplantar injection of capsaicin evoked comparable heat hyperalgesia and mechanical hypersensitivity in Nf1+/- and wild type mice of both genders. Formalin injection caused a similar duration of licking in male Nf1+/- and wild type mice. Female Nf1+/- mice licked less than wild type mice, but displayed other nociceptive behaviors. In contrast, intraplantar injection of CGRP caused greater heat hyperalgesia in Nf1+/- mice of both genders compared to wild type mice. Male Nf1+/- mice also exhibited greater mechanical hypersensitivity; however, female Nf1+/- mice exhibited less mechanical hypersensitivity than their wild type littermates. Transcripts for calcitonin gene-related peptide were similar in the dorsal root ganglia of both genotypes and genders. Transcripts for receptor activity-modifying protein-1, which is rate-limiting for the calcitonin gene-related peptide receptor, in the spinal cord were comparable for both genotypes and genders. The increased responsiveness to intraplantar calcitonin gene-related peptide suggests that the peripheral actions of calcitonin gene-related peptide are enhanced as a result of the neurofibromin deficit. The analgesic efficacy of calcitonin gene-related peptide receptor antagonists may therefore merit investigation in neurofibromatosis patients.

  13. CALCITONIN GENE-RELATED PEPTIDE INDUCES FIBROBLASTS FROM HIP PSEUDOCAPSULE TO PRODUCE CYTOKINES

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To investigate calcitonin gene-related peptide (CGRP) involvement in the process of aseptic loosening. Methods We isolated fibroblasts from periprosthetic pseudocapsular tissue at the time of revision hip arthroplasty performed due to aseptic loosening. Fibroblasts were incubated for 24 h in the presence of CGRP, and the levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the media were determined using enzyme-linked immunosorbent assay kit. Results We found that the levels of IL-1β, IL-6, and TNF-α increased in a time- and concentration-dependent manner. ConclusionThese inflammatory cytokines play an important role in the development of periprosthetic osteolysis and implant loosening. Our results suggest that CGRP may be involved in the pathogenesis of aseptic loosening.

  14. Preliminary study on androgen dependence of calcitonin gene-related peptide in rat penis

    Institute of Scientific and Technical Information of China (English)

    Zhou-Jun Shen; Shan-Wen Chen; Ying-Li Lu; Liao-Yuan Li; Xie-Lai Zhou; Ming-Guang Zhang; Zhao-Dian Chen

    2005-01-01

    Aim: To study the androgen dependence of the neurotransmitter, calcitonin gene-related peptide (CGRP) in rat penis.Methods: Forty-four Sprague-Dawley rats were randomly divided into Group A (intact controls), Group B (castrated)group were anaesthetized. Blood samples were taken for the measurement of serum testosterone and dihydrotestosterone (DHT) by means of radioimmunoassay. Penile samples were harvested for the investigation of calcitonin gene related peptide (CGRP)-immunoreactive nerve fibers with immunohistochemistry. The computer-assisted imaging analysis system was applied to calculate the area proportion of the CGRP-positive nerve fibers (CGRP-PNF) in each group.Results: 1) Both 4 and 10 weeks later, testosterone and DHT levels in Group B decreased significantly compared with those in Group A, (P<0.05, P<0.01, respectively); DHT level in Group C was also significantly decreased in comparison with that in Group A for both 4- and 10- week animals (P < 0.05); 2) There was no significant differences in area proportion of CGRP-PNF among Groups A, B and C 4 weeks after treatments (P > 0.05); However, 10weeks later, the proportion of CGRP-PNF in Groups B and C was significantly less than that in Group A (P < 0.01);3) The proportion of CGRP-PNF of 4-week animals in Groups B and C was significantly higher than that of 10-week animals (P<0.05). Conclusion: The expression of neurotransmitter, CGRP may depend on androgens, including testosterone and DHT in rat penis.

  15. Identification of potent, selective, and metabolically stable peptide antagonists to the calcitonin gene-related peptide (CGRP) receptor.

    Science.gov (United States)

    Miranda, Les P; Holder, Jerry Ryan; Shi, Licheng; Bennett, Brian; Aral, Jennifer; Gegg, Colin V; Wright, Marie; Walker, Kenneth; Doellgast, George; Rogers, Rick; Li, Hongyan; Valladares, Violeta; Salyers, Kevin; Johnson, Eileen; Wild, Kenneth

    2008-12-25

    Calcitonin gene-related peptide (CGRP) is a 37-residue neuropeptide that can be converted to a CGRP(1) receptor antagonist by the truncation of its first seven residues. CGRP(8-37), 1, has a CGRP(1) receptor K(i) = 3.2 nM but is rapidly degraded in human plasma (t(1/2) = 20 min). As part of an effort to identify a prolonged in vivo circulating CGRP peptide antagonist, we found that the substitution of multiple residues in the CGRP peptide increased CGRP(1) receptor affinity >50-fold. Ac-Trp-[Arg(24),Lys(25),Asp(31),Pro(34),Phe(35)]CGRP(8-37)-NH(2), 5 (K(i) = 0.06 nM) had the highest CGRP(1) receptor affinity. Using complimentary in vitro and in vivo metabolic studies, we iteratively identified degradation sites and prepared high affinity analogues with significantly improved plasma stability. Ac-Trp-[Cit(11,18),hArg(24),Lys(25),2-Nal(27,37),Asp(31),Oic(29,34),Phe(35)]CGRP(8-37)-NH(2), 32 (K(i) = 3.3 nM), had significantly increased (>100-fold) stability over 1 or 5, with a cynomolgus monkey and human in vitro plasma half-life of 38 and 68 h, respectively.

  16. Substance P and calcitonin gene-related peptide expression in dorsal root ganglia in sciatic nerve injury rats

    Institute of Scientific and Technical Information of China (English)

    Changma Fu; Zongsheng Yin; Defu Yu; Zuhua Yang

    2013-01-01

    The neuropeptides, substance P and calcitonin gene-related peptide, have been shown to be involved in pain transmission and repair of sciatic nerve injury. A model of sciatic nerve defect was prepared by dissecting the sciatic nerve at the middle, left femur in female Sprague Dawley rats. The two ends of the nerve were encased in a silica gel tube. L5 dorsal root ganglia were harvested 7, 14 and 28 days post sciatic nerve injury for immunohistochemical staining. Results showed that substance P and cal-citonin gene-related peptide expression increased significantly in dorsal root ganglion of rats with sci-atic nerve injury. This increase peaked at 7 days, declined at 14 days, and reduced to normal levels by 28 days post injury. The findings indicate that the neuropeptides, substance P and calcitonin gene-related peptide, mainly increased in the early stages after sciatic nerve injury.

  17. Role for voltage gated calcium channels in calcitonin gene-related peptide release in the rat trigeminovascular system

    DEFF Research Database (Denmark)

    Amrutkar, D V; Ploug, K B; Olesen, J

    2011-01-01

    Clinical and genetic studies have suggested a role for voltage gated calcium channels (VGCCs) in the pathogenesis of migraine. Release of calcitonin gene-related peptide (CGRP) from trigeminal neurons has also been implicated in migraine. The VGCCs are located presynaptically on neurons and are i...... releases CGRP, and the release is regulated by Ca2+ ions and voltage-gated calcium channels.......Clinical and genetic studies have suggested a role for voltage gated calcium channels (VGCCs) in the pathogenesis of migraine. Release of calcitonin gene-related peptide (CGRP) from trigeminal neurons has also been implicated in migraine. The VGCCs are located presynaptically on neurons...

  18. Isolation and molecular characterization of porcine calcitonin gene-related peptide (CGRP) and its endocrine effects in the porcine pancreas

    DEFF Research Database (Denmark)

    Rasmussen, T N; Bersani, M; Schmidt, P;

    1998-01-01

    The aim of this study was to investigate the possible role of porcine calcitonin gene-related peptide (CGRP) in the regulation of the endocrine porcine pancreas. Initially, we isolated and purified CGRP from extracts of porcine adrenal glands and pancreases. A single molecular form of the peptide...... was found in the two tissues. The adrenal peptide was sequenced and found to differ from human alpha-CGRP at six positions and from human beta-CGRP at three positions. By immunohistochemistry, CGRP was found in nerve fibers in the pancreatic ganglia. A synthetic replica of the porcine peptide was infused...

  19. Role for voltage gated calcium channels in calcitonin gene-related peptide release in the rat trigeminovascular system

    DEFF Research Database (Denmark)

    Amrutkar, D V; Ploug, K B; Olesen, J;

    2011-01-01

    Clinical and genetic studies have suggested a role for voltage gated calcium channels (VGCCs) in the pathogenesis of migraine. Release of calcitonin gene-related peptide (CGRP) from trigeminal neurons has also been implicated in migraine. The VGCCs are located presynaptically on neurons and are i...

  20. Dilatory responses to acetylcholine, calcitonin gene-related peptide and substance P in the congestive heart failure rat

    DEFF Research Database (Denmark)

    Bergdahl, A; Valdemarsson, S; Nilsson, T;

    1999-01-01

    It was examined to what extent congestive heart failure (CHF) in rats, induced by ligation of the left coronary artery, affects the vascular responses to the vasodilatory substances acetylcholine (ACh), calcitonin gene-related peptide (CGRP), and substance P (SP). After induction of CHF status...

  1. EXPRESSION OF CALCITONIN GENE-RELATED PEPTIDE IN FACIAL NERVE OF HEMIFACIAL SPASM

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To study the immunoreactivity of Calcitonin gene-related peptide (CGRP) in the facial nerve when Hemifacial Spasm is occurring. Methods The electrophysiological technique was used to explore abnormal muscle response (AMR) which was characteristic of Hemifacial Spasm.The animal models of Hemifacial Spasm in New Zealand white rabbits were established by compressing the main trunk of artificial demyelinated facial nerve with the temporal superficial artery. At 6 weeks after surgery, the facial nerves were taken from the experimental group and control one, the immunohistochemistry for CGRP using polyclonal antibody with ABC kit was performed in the facial nerves; at the same time, the observation for the facial nerves of light and transmission electron microscope was performed. Results The facial nerve demyelinated and the axons retrogressively changed, CGRP immunoreactive positive fibers were significantly detected in experimental groups; whereas this phenomenon was not found in control group. Conclusion CGRP can nutrien the injured facial nerve and plays an important role in the pathogenesis of Hemifacial Spasm.

  2. Calcitonin gene-related peptide in the joint: contributions to pain and inflammation.

    Science.gov (United States)

    Walsh, David A; Mapp, Paul I; Kelly, Sara

    2015-11-01

    Arthritis is the commonest cause of disabling chronic pain, and both osteoarthritis (OA) and rheumatoid arthritis (RA) remain major burdens on both individuals and society. Peripheral release of calcitonin gene-related peptide (CGRP) contributes to the vasodilation of acute neurogenic inflammation. Contributions of CGRP to the pain and inflammation of chronic arthritis, however, are only recently being elucidated. Animal models of arthritis are revealing the molecular and pathophysiological events that accompany and lead to progression of both arthritis and pain. Peripheral actions of CGRP in the joint might contribute to both inflammation and joint afferent sensitization. CGRP and its specific receptors are expressed in joint afferents and up-regulated following arthritis induction. Peripheral CGRP release results in activation of synovial vascular cells, through which acute vasodilatation is followed by endothelial cell proliferation and angiogenesis, key features of chronic inflammation. Local administration of CGRP to the knee also increases mechanosensitivity of joint afferents, mimicking peripheral sensitization seen in arthritic joints. Increased mechanosensitivity in OA knees and pain behaviour can be reduced by peripherally acting CGRP receptor antagonists. Effects of CGRP pathway blockade on arthritic joint afferents, but not in normal joints, suggest contributions to sensitization rather than normal joint nociception. CGRP therefore might make key contributions to the transition from normal to persistent synovitis, and the progression from nociception to sensitization. Targeting CGRP or its receptors within joint tissues to prevent these undesirable transitions during early arthritis, or suppress them in established disease, might prevent persistent inflammation and relieve arthritis pain.

  3. Substance P and Calcitonin Gene-Related Peptide: Key Regulators of Cutaneous Microbiota Homeostasis

    Science.gov (United States)

    N’Diaye, Awa; Gannesen, Andrei; Borrel, Valérie; Maillot, Olivier; Enault, Jeremy; Racine, Pierre-Jean; Plakunov, Vladimir; Chevalier, Sylvie; Lesouhaitier, Olivier; Feuilloley, Marc G. J.

    2017-01-01

    Neurohormones diffuse in sweat and epidermis leading skin bacterial microflora to be largely exposed to these host factors. Bacteria can sense a multitude of neurohormones, but their role in skin homeostasis was only investigated recently. The first study focused on substance P (SP), a neuropeptide produced in abundance by skin nerve terminals. SP is without effect on the growth of Gram-positive (Bacillus cereus, Staphylococcus aureus, and Staphylococcus epidermidis) and Gram-negative (Pseudomonas fluorescens) bacteria. However, SP is stimulating the virulence of Bacillus and Staphylococci. The action of SP is highly specific with a threshold below the nanomolar level. Mechanisms involved in the response to SP are different between bacteria although they are all leading to increased adhesion and/or virulence. The moonlighting protein EfTu was identified as the SP-binding site in B. cereus and Staphylococci. In skin nerve terminals, SP is co-secreted with the calcitonin gene-related peptide (CGRP), which was shown to modulate the virulence of S. epidermidis. This effect is antagonized by SP. Identification of the CGRP sensor, DnaK, allowed understanding this phenomenon as EfTu and DnaK are apparently exported from the bacterium through a common system before acting as SP and CGRP sensors. Many other neuropeptides are expressed in skin, and their potential effects on skin bacteria remain to be investigated. Integration of these host signals by the cutaneous microbiota now appears as a key parameter in skin homeostasis. PMID:28194136

  4. Comparison of Calcitonin Gene Related Peptide Level between Children with Dilated Cardiomyopathy and Control Group

    Directory of Open Access Journals (Sweden)

    Noormohammad Noori

    2015-06-01

    Full Text Available Background: Dilated cardiomyopathy is revealed with left ventricular dilatation and systolic dysfunction. Objectives: This study aimed to compare the children with dilated cardiomyopathy and control group regarding the level of Calcitonin Gene Related Peptide (CGRP and its relationship with echocardiography findings Patients and Methods: This case-control study was conducted on 37 children with dilated cardiomyopathy and free of any clinical symptoms and 37 healthy age- and sex-matched children referring to Ali-e-Asghar and Ali Ebne Abitaleb hospitals in Zahedan, Iran. After taking history, echocardiography was performed for both groups. The data were analyzed using the SPSS statistical software and appropriate statistical tests. Results: The two groups were significantly different regarding most of the echocardiographic parameters (P < 0.05. Also, a significant difference was found between the two groups concerning the mean CGRP levels (P = 0.001. Among echocardiographic parameters, CGRP was directly related to Interventricular Septal dimension in Systole (IVSS (P = 0.022, R = 0.375. However, no significant relationship was observed between CGRP level and Ross classification. Conclusions: The findings of this study showed an increase in CGRP serum levels in the case group. Besides, a direct correlation was observed between CGRP level and IVSS.

  5. Calcitonin gene-related peptide regulates type IV hypersensitivity through dendritic cell functions.

    Directory of Open Access Journals (Sweden)

    Norihisa Mikami

    Full Text Available Dendritic cells (DCs play essential roles in both innate and adaptive immune responses. In addition, mutual regulation of the nervous system and immune system is well studied. One of neuropeptides, calcitonin gene-related peptide (CGRP, is a potent regulator in immune responses; in particular, it has anti-inflammatory effects in innate immunity. For instance, a deficiency of the CGRP receptor component RAMP 1 (receptor activity-modifying protein 1 results in higher cytokine production in response to LPS (lipopolysaccharide. On the other hand, how CGRP affects DCs in adaptive immunity is largely unknown. In this study, we show that CGRP suppressed Th1 cell differentiation via inhibition of IL-12 production in DCs using an in vitro co-culture system and an in vivo ovalbumin-induced delayed-type hypersensitivity (DTH model. CGRP also down-regulated the expressions of chemokine receptor CCR2 and its ligands CCL2 and CCL12 in DCs. Intriguingly, the frequency of migrating CCR2(+ DCs in draining lymph nodes of RAMP1-deficient mice was higher after DTH immunization. Moreover, these CCR2(+ DCs highly expressed IL-12 and CD80, resulting in more effective induction of Th1 differentiation compared with CCR2(- DCs. These results indicate that CGRP regulates Th1 type reactions by regulating expression of cytokines, chemokines, and chemokine receptors in DCs.

  6. Calcitonin Gene-Related Peptide Modulates Heat Nociception in the Human Brain - An fMRI Study in Healthy Volunteers

    DEFF Research Database (Denmark)

    Asghar, Mohammad Sohail; Becerra, Lino; Larsson, Henrik B W

    2016-01-01

    BACKGROUND: Intravenous infusion of calcitonin-gene-related-peptide (CGRP) provokes headache and migraine in humans. Mechanisms underlying CGRP-induced headache are not fully clarified and it is unknown to what extent CGRP modulates nociceptive processing in the brain. To elucidate this we record...... cortex. Sumatriptan injection reversed these changes. CONCLUSION: The changes in BOLD-signals in the brain after CGRP infusion suggests that systemic CGRP modulates nociceptive transmission in the trigeminal pain pathways in response to noxious heat stimuli.......BACKGROUND: Intravenous infusion of calcitonin-gene-related-peptide (CGRP) provokes headache and migraine in humans. Mechanisms underlying CGRP-induced headache are not fully clarified and it is unknown to what extent CGRP modulates nociceptive processing in the brain. To elucidate this we recorded...

  7. Calcitonin gene-related peptide (CGRP) regulates excitability and refractory period of the guinea pig ureter.

    Science.gov (United States)

    Maggi, C A; Giuliani, S

    1994-08-01

    Previous studies have indicated that calcitonin gene-related peptide (CGRP), released from the peripheral endings of capsaicin-sensitive primary afferent neurons, may play a role as an inhibitory transmitter in the guinea pig ureter. The aim of this study was to compare the effect of capsaicin desensitization and administration of a CGRP receptor antagonist on the excitability and refractory period of the guinea pig ureter to electrical field stimulation. Electrical field stimulation using a long (5 msec.) pulse width produced phasic contractions of the ureter which were unaffected by tetrodotoxin, that is, were produced through direct excitation of ureteral smooth muscle. Human alpha CGRP (1 to 10 nM.) produced a concentration-dependent transient suppression of the evoked contractions, and its effect was prevented by the CGRP receptor antagonist human alpha CGRP(8-37) (1 microM.). In vitro capsaicin pretreatment (10 microM. for 15 minutes) to block neuropeptide release from peripheral endings of sensory nerves or administration of the CGRP receptor antagonist enhanced the responsiveness of the guinea pig ureter to electrical stimulation. In control ureters, the application of two trains of electrical stimuli failed to produce a second contraction at intertrain intervals greater than 20 seconds. The intertrain interval required to obtain a second contraction averaging 50% of the amplitude of the first response (ITI50) of control ureters was about 50 seconds. In vitro capsaicin pretreatment or administration of the CGRP receptor antagonist reduced the refractory period of the ureter to electrical field stimulation: ITI50 averaged 8.8 and 9.1 seconds after capsaicin or CGRP antagonist pretreatment, respectively. These findings demonstrate that capsaicin pretreatment or blockade of CGRP receptors produced qualitatively and quantitatively similar excitatory effects on ureteral excitability and refractory period and are in general agreement with the idea that CGRP is a

  8. Calcitonin gene-related peptide expression is altered in pulmonary neuroendocrine cells in developing lungs of rats with congenital diaphragmatic hernia

    NARCIS (Netherlands)

    H. IJsselstijn (Hanneke); N. Hung; J.C. de Jongste (Johan); D. Tibboel (Dick); E. Cutz

    1998-01-01

    textabstractCongenital diaphragmatic hernia (CDH) is associated with high neonatal mortality from lung hypoplasia and persistent pulmonary hypertension. Pulmonary neuroendocrine cells (PNEC) produce calcitonin gene-related peptide (CGRP), a potent vasodilator. We previo

  9. Substance P and Calcitonin Gene Related Peptide Mediate Pain in Chronic Pancreatitis and Their Expression is Driven by Nerve Growth Factor

    Science.gov (United States)

    Liu, LianSheng; Shenoy, Mohan; Pasricha, Pankaj Jay

    2014-01-01

    Context Calcitonin gene-related peptide (CGRP), substance P and nerve growth factor play an important role in inflammatory pain in various somatic pain models but their role in chronic pancreatitis has not been well studied. Objectives The aim of this study was to investigate the effects of intrathecal administration of calcitonin gene-related peptide antagonist and substance P receptor antagonist on pain behavior in a rat model of chronic pancreatitis and to determine whether nerve growth factor drives the up-regulation of expression of these neuropeptides in sensory neurons. Methods Pancreatitis was induced by retrograde infusion of trinitobenzene sulfonic acid into the pancreatic duct of adult rats. Three weeks post infusion continuous intrathecal infusion of the calcitonin gene-related peptide antagonist alpha CGRP8-37 or neurokinin-1 receptor antagonist CP-96345 or its inactive enantiomer CP-96344 was administered for seven days. The effects of treatment on pancreatic hyperalgesia were assessed by sensitivity of the abdominal wall to von Frey filament probing as well as by the nocifensive response to electrical stimulation of the pancreas. In a separate experiment chronic pancreatitis was induced and pancreas specific dorsal root ganglion neurons labeled with DiI were assessed for calcitonin gene-related peptide and substance P immunoreactivity. Results Intrathecal infusion of calcitonin gene-related peptide and neurokinin-1 receptor antagonists significantly attenuated behavioral pain responses in rats with chronic pancreatitis. Further, treatment of chronic pancreatitis rats with nerve growth factor antibody significantly reduced pancreas specific neurons expressing calcitonin gene-related peptide and substance P in thoracic dorsal root ganglion. Conclusions Calcitonin gene-related peptide and substance P mediate pancreatic hyperalgesia in chronic pancreatitis and nerve growth factor in turn sustains the up-regulation of these neuropeptides in pancreatic

  10. Relaxant effect of the calcitonin gene-related peptide (CGRP) on the nonpregnant and pregnant rat uterus. Comparison with vascular tissue.

    Science.gov (United States)

    Anouar, A; Schirar, A; Germain, G

    1998-04-01

    To explore the role of calcitonin gene-related peptide (CGRP) in rat pregnancy, we determined the density of myometrial CGRP-encoded nerve fibre terminals and examined, in an organ bath, the relaxant effect of the peptide on uterine strips near parturition. Comparisons were made with the uterus and aorta of nonpregnant rats. In the myometrium, CGRP immunoreactive nerve fibers were abundant in nonpregnant rats and scarce at the parturient stage. In the aorta there was no variation in the density of CGRP fibres with gestation. In nonpregnant rats only, CGRP relaxed spontaneous and tetrodotoxin (TTX)-sensitive electrically-evoked uterine contractions (EC50 40 nM, Emax 80%). The effect was antagonized by CGRP[8-37] (pKB 6.47) but was not affected by either blockers of nitricoxid synthase or ATP-sensitive potassium channels. CGRP was also able to relax contractions evoked by direct depolarization of the cells (TTX-insensitive contractions) (EC50, 2 nM, Emax 70%). In aorta contracted with arginine vasopressin, CGRP-induced relaxation was the same in nonpregnant and parturient animals. It was antagonized by CGRP [8-371 (pKB 6.90) and was abolished in presence of the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME). Amylin neither relaxed the uterus nor the aorta. In pregnant rats, the relaxant effect of CGRP on the uterus was limited on day 21 and was totally absent on day 22 of gestation. We conclude that the primary relaxant effect of CGRP on the uterus occurs at the level of myometrial smooth muscle cells. In the myometrium, gestation decreases CGRP innervation and impairs the relaxant responses to CGRP. Such changes are not observed in vascular tissues like aorta.

  11. Calcitonin gene-related peptide and its receptor components in the human sphenopalatine ganglion -- interaction with the sensory system

    DEFF Research Database (Denmark)

    Csati, Anett; Tajti, Janos; Tuka, Bernadett

    2012-01-01

    receptor-like receptor (CLR) and the receptor activity modifying protein 1 (RAMP1) in human and rat SPG. Cryostat sections were examined and images were obtained using a light- and epifluorescence microscope coupled to a camera to visualize co-labeling by superimposing the digital images. In addition......Clinical studies have suggested a link between the sensory trigeminal system and the parasympathetic ganglia. Calcitonin gene-related peptide (CGRP) is a sensory neuropeptide which plays an important role in vasodilatation and pain transmission in craniocervical structures. The present study...... was designed to examine if CGRP and CGRP receptor components are present in the human sphenopalatine ganglion (SPG) in order to reveal an interaction between the sensory and parasympathetic systems. Indirect immunofluorescence technique was used for immunohistochemical demonstration of CGRP, the calcitonin...

  12. Application of shock waves to rat skin decreases calcitonin gene-related peptide immunoreactivity in dorsal root ganglion neurons.

    Science.gov (United States)

    Takahashi, Norimasa; Wada, Yuichi; Ohtori, Seiji; Saisu, Takashi; Moriya, Hideshige

    2003-09-30

    There have been several reports on the use of extracorporeal shock waves in the treatment of pseudarthrosis, calcifying tendinitis, and tendinopathies of the elbow. However, the pathomechanism of pain relief has not been clarified. To investigate the analgesic properties of shock wave application, we analyzed changes in calcitonin gene-related peptide (CGRP)-immunoreactive (ir) dorsal root ganglion (DRG) neurons. In the nontreated group, fluorogold-labeled dorsal root ganglion neurons innervating the most middle foot pad of hind paw were distributed in the L4 and L5 dorsal root ganglia. Of these neurons, 61% were CGRP-ir. However, in the shock wave-treated group, the percentage of FG-labeled CGRP-ir DRG neurons decreased to 18%. These data show that relief of clinical pain after shock wave application may result from reduced CGRP expression in DRG neurons.

  13. Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients

    DEFF Research Database (Denmark)

    Lassen, L.H.; Jacobsen, V.B.; Haderslev, P.A.

    2008-01-01

    g/min) or placebo for 20 min was studied in 12 patients with migraine without aura outside attacks. Xenon-133 inhalation SPECT-determined regional cerebral blood flow (rCBF) and transcranial Doppler (TCD)-determined blood velocity (V-mean) in the middle cerebral artery (MCA), as well as the heart......Calcitonin gene-related peptide (CGRP)-containing nerves are closely associated with cranial blood vessels. CGRP is the most potent vasodilator known in isolated cerebral blood vessels. CGRP can induce migraine attacks, and two selective CGRP receptor antagonists are effective in the treatment...... of migraine attacks. It is therefore important to investigate its mechanism of action in patients with migraine. We here investigate the effects of intravenous human alpha-CGRP (h alpha CGRP) on intracranial hemodynamics. In a double-blind, cross-over study, the effect of intravenous infusion of haCGRP (2 mu...

  14. Calcitonin gene-related peptide promotes cellular changes in trigeminal neurons and glia implicated in peripheral and central sensitization

    Directory of Open Access Journals (Sweden)

    Cady Ryan J

    2011-12-01

    Full Text Available Abstract Background Calcitonin gene-related peptide (CGRP, a neuropeptide released from trigeminal nerves, is implicated in the underlying pathology of temporomandibular joint disorder (TMD. Elevated levels of CGRP in the joint capsule correlate with inflammation and pain. CGRP mediates neurogenic inflammation in peripheral tissues by increasing blood flow, recruiting immune cells, and activating sensory neurons. The goal of this study was to investigate the capability of CGRP to promote peripheral and central sensitization in a model of TMD. Results Temporal changes in protein expression in trigeminal ganglia and spinal trigeminal nucleus were determined by immunohistochemistry following injection of CGRP in the temporomandibular joint (TMJ capsule of male Sprague-Dawley rats. CGRP stimulated expression of the active forms of the MAP kinases p38 and ERK, and PKA in trigeminal ganglia at 2 and 24 hours. CGRP also caused a sustained increase in the expression of c-Fos neurons in the spinal trigeminal nucleus. In contrast, levels of P2X3 in spinal neurons were only significantly elevated at 2 hours in response to CGRP. In addition, CGRP stimulated expression of GFAP in astrocytes and OX-42 in microglia at 2 and 24 hours post injection. Conclusions Our results demonstrate that an elevated level of CGRP in the joint, which is associated with TMD, stimulate neuronal and glial expression of proteins implicated in the development of peripheral and central sensitization. Based on our findings, we propose that inhibition of CGRP-mediated activation of trigeminal neurons and glial cells with selective non-peptide CGRP receptor antagonists would be beneficial in the treatment of TMD.

  15. Localization of large conductance calcium-activated potassium channels and their effect on calcitonin gene-related peptide release in the rat trigemino-neuronal pathway

    DEFF Research Database (Denmark)

    Wulf-Johansson, H.; Amrutkar, D.V.; Hay-Schmidt, Anders

    2010-01-01

    Large conductance calcium-activated potassium (BK(Ca)) channels are membrane proteins contributing to electrical propagation through neurons. Calcitonin gene-related peptide (CGRP) is a neuropeptide found in the trigeminovascular system (TGVS). Both BK(Ca) channels and CGRP are involved in migraine...

  16. Contribution of kv7.4/kv7.5 heteromers to intrinsic and calcitonin gene-related Peptide-induced cerebral reactivity

    DEFF Research Database (Denmark)

    Chadha, Preet S; Jepps, Thomas A; Carr, Georgina;

    2014-01-01

    Middle cerebral artery (MCA) diameter is regulated by inherent myogenic activity and the effect of potent vasodilators such as calcitonin gene-related peptide (CGRP). Previous studies showed that MCAs express KCNQ1, 4, and 5 potassium channel genes, and the expression products (Kv7 channels) part...

  17. Exercise alleviates hypoalgesia and increases the level of calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats

    Directory of Open Access Journals (Sweden)

    Patrícia Severo do Nascimento

    2012-09-01

    Full Text Available OBJECTIVE: The aim of this study was to evaluate the effects of treadmill training on nociceptive sensitivity and immunoreactivity to calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats. METHODS: Male Wistar rats were divided into three groups: control, diabetic and trained diabetic. Treadmill training was performed for 8 weeks. The blood glucose concentrations and body weight were evaluated 48 h after diabetes induction and every 30 days thereafter. The nociceptive sensitivity was evaluated using the tail-flick apparatus. The animals were then transcardially perfused, and the spinal cords were post-fixed, cryoprotected and sectioned in a cryostat. Immunohistochemistry for calcitonin gene-related peptide analysis was performed on the dorsal horn of the spinal cord. RESULTS: The nociceptive sensitivity analysis revealed that, compared with the control and trained diabetic animals, the latency to tail deflection on the apparatus was longer for the diabetic animals. Optical densitometry demonstrated decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord in diabetic animals, which was reversed by treadmill training. CONCLUSION: We concluded that treadmill training can alleviate nociceptive hypoalgesia and reverse decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord of diabetic animals without pharmacological treatment.

  18. Is there an inherent limit to the efficacy of calcitonin gene-related peptide receptor antagonists in the acute treatment of migraine? A comment

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer C

    2009-01-01

    Calcitonin gene-related peptide (CGRP) receptor antagonists are a new treatment principle in acute migraine attacks. Intravenous olcegepant 2.5 mg resulted in 66% headache relief after 2 h, whereas subcutaneous sumatriptan resulted in 81-92% headache relief after 2 h. The intrinsic activity...

  19. Overexpression and Purification of Human Calcitonin Gene Related Peptide - Receptor Component Protein (CGRP-RCP) in Escherichia coli

    Science.gov (United States)

    Tolun, Adviye A.; Dickerson, Ian M.; Malhotra, Arun

    2007-01-01

    Calcitonin gene-related peptide (CGRP) is a neuropeptide secreted by the central and peripheral nervous system nerves that has important physiological functions such as vasodilation, cardiotonic actions, metabolic and pro-inflammatory effects. The CGRP receptor is unique among G-protein coupled receptors in that a functional CGRP receptor consists of at least three proteins: Calcitonin Like Receptor (CLR), Receptor Activity Modifying Protein (RAMP1) and Receptor Component Protein (RCP). RCP is a required factor in CGRP-mediated signal transduction and it couples the CGRP receptor to the signal transduction pathway. Here we describe methods to overexpress and purify RCP for structure-function studies. Human RCP was cloned and overexpressed with a poly-histidine tag and as a Maltose Binding Protein (MBP) fusion in Escherichia coli using commercially available expression vectors. While his-tagged RCP is prone to aggregation, solubility is improved when RCP is expressed as a MBP fusion. Expression and purification procedures for these constructs are described. Results from these studies will facilitate structural analysis of human RCP, and allow further understanding of RCP function. PMID:17067815

  20. Characterization and localization of the rabbit ocular calcitonin gene-related peptide (CGRP)-receptor component protein (RCP).

    Science.gov (United States)

    Rosenblatt, M I; Dahl, G P; Dickerson, I M

    2000-04-01

    To determine whether the calcitonin gene-related peptide (CGRP) receptor component protein (RCP), a novel signal transduction molecule, is required for CGRP signaling in the eye and to determine potential ocular sites of CGRP action. The cDNA for the rabbit ocular RCP homologue was cloned using a combination of reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE). Function of the rabbit ocular RCP was assessed using a sensitive oocyte-based assay, which utilizes the protein kinase A (PKA)-sensitive cystic fibrosis transmembrane conductance regulator (CFTR) as a sensor of cAMP formation. RCP expression in the rabbit eye was localized using immunohistochemistry. A 2063-bp cDNA for the rabbit ocular RCP was cloned and sequenced. Expression of the rabbit RCP cDNA confers CGRP responsiveness in a sensitive oocyte-based assay. Antisense oligonucleotides made to the ocular RCP abolishes CGRP responsiveness of ciliary body and iris mRNA in the oocyte-CFTR assay. Localization of RCP protein in the rabbit eye using immunohistochemistry demonstrated RCP immunoreactivity in the ciliary body and iris blood vessels, as well as in layers of the ciliary epithelium. The rabbit ocular RCP appears to be required for signal transduction at ocular CGRP receptors and is localized to sites previously reported to bind CGRP, which affect intraocular pressure and neurogenic inflammation.

  1. Expression pattern of sonic hedgehog signaling and calcitonin gene-related peptide in the socket healing process after tooth extraction.

    Science.gov (United States)

    Pang, Pai; Shimo, Tsuyoshi; Takada, Hiroyuki; Matsumoto, Kenichi; Yoshioka, Norie; Ibaragi, Soichiro; Sasaki, Akira

    2015-11-06

    Sonic Hedgehog (SHH), a neural development inducer, plays a significant role in the bone healing process. Calcitonin gene-related peptide (CGRP), a neuropeptide marker of sensory nerves, has been demonstrated to affect bone formation. The roles of SHH signaling and CGRP-positive sensory nerves in the alveolar bone formation process have been unknown. Here we examined the expression patterns of SHH signaling and CGRP in mouse socket by immunohistochemistry and immunofluorescence analysis. We found that the expression level of SHH peaked at day 3 and was then decreased at 5 days after tooth extraction. CGRP, PTCH1 and GLI2 were each expressed in a similar pattern with their highest expression levels at day 5 and day 7 after tooth extraction. CGRP and GLI2 were co-expressed in some inflammatory cells and bone forming cells. In some areas, CGRP-positive neurons expressed GLI2. In conclusion, SHH may affect alveolar bone healing by interacting with CGRP-positive sensory neurons and thus regulate the socket's healing process after tooth extraction.

  2. Calcitonin gene-related peptide regulation of glial cell-line derived neurotrophic factor in differentiated rat myotubes.

    Science.gov (United States)

    Rosa, Elyse; Cha, Jieun; Bain, James R; Fahnestock, Margaret

    2015-03-01

    Glial cell-line derived neurotrophic factor (GDNF) is the most potent trophic factor for motoneuron survival and neuromuscular junction formation. GDNF is upregulated in injured or denervated skeletal muscle and returns to normal levels following reinnervation. However, the mechanism by which GDNF is regulated in denervated muscle is not well understood. The nerve-derived neurotransmitter calcitonin gene-related peptide (CGRP) is upregulated following neuromuscular injury and is subsequently released from motoneurons at the neuromuscular junction. CGRP also promotes nerve regeneration, but the mechanism is not well understood. The current study investigates whether this increase in CGRP regulates GDNF, thus playing a key role in promoting regeneration of injured nerves. This study demonstrates that CGRP increases GDNF secretion without affecting its transcription or translation. Rat L6 myoblasts were differentiated into myotubes and subsequently treated with CGRP. GDNF mRNA expression levels were quantified by quantitative real-time reverse transcription-polymerase chain reaction, and secreted GDNF was quantified in the conditioned medium by ELISA. CGRP treatment increased secreted GDNF protein without altering GDNF mRNA levels. The translational inhibitor cycloheximide did not affect CGRP-induced GDNF secreted protein levels, whereas the secretional inhibitor brefeldin A blocked the CGRP-induced increase in GDNF. This study highlights the importance of injury-induced upregulation of CGRP by exposing its ability to increase GDNF levels and demonstrates a secretional mechanism for regulation of this key regeneration-promoting neurotrophic factor.

  3. Statins decrease expression of the proinflammatory neuropeptides calcitonin gene-related peptide and substance P in sensory neurons.

    Science.gov (United States)

    Bucelli, Robert C; Gonsiorek, Eugene A; Kim, Woo-Yang; Bruun, Donald; Rabin, Richard A; Higgins, Dennis; Lein, Pamela J

    2008-03-01

    Clinical and experimental observations suggest that statins may be useful for treating diseases presenting with predominant neurogenic inflammation, but the mechanism(s) mediating this potential therapeutic effect are poorly understood. In this study, we tested the hypothesis that statins act directly on sensory neurons to decrease expression of proinflammatory neuropeptides that trigger neurogenic inflammation, specifically calcitonin gene-related peptide (CGRP) and substance P. Reverse transcriptase-polymerase chain reaction, radioimmunoassay, and immunocytochemistry were used to quantify CGRP and substance P expression in dorsal root ganglia (DRG) harvested from adult male rats and in primary cultures of sensory neurons derived from embryonic rat DRG. Systemic administration of statins at pharmacologically relevant doses significantly reduced CGRP and substance P levels in DRG in vivo. In cultured sensory neurons, statins blocked bone morphogenetic protein (BMP)-induced CGRP and substance P expression and decreased expression of these neuropeptides in sensory neurons pretreated with BMPs. These effects were concentration-dependent and occurred independent of effects on cell survival or axon growth. Statin inhibition of neuropeptide expression was reversed by supplementation with mevalonate and cholesterol, but not isoprenoid precursors. BMPs signal via Smad activation, and cholesterol depletion by statins inhibited Smad1 phosphorylation and nuclear translocation. These findings identify a novel action of statins involving down-regulation of proinflammatory neuropeptide expression in sensory ganglia via cholesterol depletion and decreased Smad1 activation and suggest that statins may be effective in attenuating neurogenic inflammation.

  4. Immature osteoblastic MG63 cells possess two calcitonin gene-related peptide receptor subtypes that respond differently to [Cys(Acm)(2,7)] calcitonin gene-related peptide and CGRP(8-37).

    Science.gov (United States)

    Kawase, Tomoyuki; Okuda, Kazuhiro; Burns, Douglas M

    2005-10-01

    Calcitonin gene-related peptide (CGRP) is clearly an anabolic factor in skeletal tissue, but the distribution of CGRP receptor (CGRPR) subtypes in osteoblastic cells is poorly understood. We previously demonstrated that the CGRPR expressed in osteoblastic MG63 cells does not match exactly the known characteristics of the classic subtype 1 receptor (CGRPR1). The aim of the present study was to further characterize the MG63 CGRPR using a selective agonist of the putative CGRPR2, [Cys(Acm)(2,7)]CGRP, and a relatively specific antagonist of CGRPR1, CGRP(8-37). [Cys(Acm)(2,7)]CGRP acted as a significant agonist only upon ERK dephosphorylation, whereas this analog effectively antagonized CGRP-induced cAMP production and phosphorylation of cAMP response element-binding protein (CREB) and p38 MAPK. Although it had no agonistic action when used alone, CGRP(8-37) potently blocked CGRP actions on cAMP, CREB, and p38 MAPK but had less of an effect on ERK. Schild plot analysis of the latter data revealed that the apparent pA2 value for ERK is clearly distinguishable from those of the other three plots as judged using the 95% confidence intervals. Additional assays using 3-isobutyl-1-methylxanthine or the PKA inhibitor N-(2-[p-bromocinnamylamino]ethyl)-5-isoquinolinesulfonamide hydrochloride (H-89) indicated that the cAMP-dependent pathway was predominantly responsible for CREB phosphorylation, partially involved in ERK dephosphorylation, and not involved in p38 MAPK phosphorylation. Considering previous data from Scatchard analysis of [125I]CGRP binding in connection with these results, these findings suggest that MG63 cells possess two functionally distinct CGRPR subtypes that show almost identical affinity for CGRP but different sensitivity to CGRP analogs: one is best characterized as a variation of CGRPR1, and the second may be a novel variant of CGRPR2.

  5. CGRP-RCP, a novel protein required for signal transduction at calcitonin gene-related peptide and adrenomedullin receptors.

    Science.gov (United States)

    Evans, B N; Rosenblatt, M I; Mnayer, L O; Oliver, K R; Dickerson, I M

    2000-10-06

    It is becoming clear that receptors that initiate signal transduction by interacting with G-proteins do not function as monomers, but often require accessory proteins for function. Some of these accessory proteins are chaperones, required for correct transport of the receptor to the cell surface, but the function of many accessory proteins remains unknown. We determined the role of an accessory protein for the receptor for calcitonin gene-related peptide (CGRP), a potent vasodilator neuropeptide. We have previously shown that this accessory protein, the CGRP-receptor component protein (RCP), is expressed in CGRP responsive tissues and that RCP protein expression correlates with the biological efficacy of CGRP in vivo. However, the function of RCP has remained elusive. In this study stable cell lines were made that express antisense RCP RNA, and CGRP- and adrenomedullin-mediated signal transduction were greatly reduced. However, the loss of RCP did not effect CGRP binding or receptor density, indicating that RCP did not behave as a chaperone but was instead coupling the CGRP receptor to downstream effectors. A candidate CGRP receptor named calcitonin receptor-like receptor (CRLR) has been identified, and in this study RCP co-immunoprecipitated with CRLR indicating that these two proteins interact directly. Since CGRP and adrenomedullin can both signal through CRLR, which has been previously shown to require a chaperone protein for function, we now propose that a functional CGRP or adrenomedullin receptor consists of at least three proteins: the receptor (CRLR), the chaperone protein (RAMP), and RCP that couples the receptor to the cellular signal transduction pathway.

  6. Effect of calcitonin gene-related peptide on the neurogenesis of rat adipose-derived stem cells in vitro.

    Directory of Open Access Journals (Sweden)

    Qin Yang

    Full Text Available Calcitonin gene-related peptide (CGRP promotes neuron recruitment and neurogenic activity. However, no evidence suggests that CGRP affects the ability of stem cells to differentiate toward neurogenesis. In this study, we genetically modified rat adipose-derived stem cells (ADSCs with the CGRP gene (CGRP-ADSCs and subsequently cultured in complete neural-induced medium. The formation of neurospheres, cellular morphology, and proliferative capacity of ADSCs were observed. In addition, the expression of the anti-apoptotic protein Bcl-2 and special markers of neural cells, such as Nestin, MAP2, RIP and GFAP, were evaluated using Western blot and immunocytochemistry analysis. The CGRP-ADSCs displayed a greater proliferation than un-transduced (ADSCs and Vector-transduced (Vector-ADSCs ADSCs (p<0.05, and lower rates of apoptosis, associated with the incremental expression of Bcl-2, were also observed for CGRP-ADSCs. Moreover, upon neural induction, CGRP-ADSCs formed markedly more and larger neurospheres and showed round cell bodies with more branching extensions contacted with neighboring cells widely. Furthermore, the expression levels of Nestin, MAP2, and RIP in CGRP-ADSCs were markedly increased, resulting in higher levels than the other groups (p<0.05; however, GFAP was distinctly undetectable until day 7, when slight GFAP expression was detected among all groups. Wnt signals, primarily Wnt 3a, Wnt 5a and β-catenin, regulate the neural differentiation of ADSCs, and CGRP gene expression apparently depends on canonical Wnt signals to promote the neurogenesis of ADSCs. Consequently, ADSCs genetically modified with CGRP exhibit stronger potential for differentiation and neurogenesis in vitro, potentially reflecting the usefulness of ADSCs as seed cells in therapeutic strategies for spinal cord injury.

  7. Is there an inherent limit to the efficacy of calcitonin gene-related peptide receptor antagonists in the acute treatment of migraine? A comment

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer C

    2009-01-01

    Calcitonin gene-related peptide (CGRP) receptor antagonists are a new treatment principle in acute migraine attacks. Intravenous olcegepant 2.5 mg resulted in 66% headache relief after 2 h, whereas subcutaneous sumatriptan resulted in 81-92% headache relief after 2 h. The intrinsic activity...... antagonism results in success in the acute treatment of migraine in only a certain fraction of the patients....

  8. The Influence of Low Doses of Zearalenone and T-2 Toxin on Calcitonin Gene Related Peptide-Like Immunoreactive (CGRP-LI Neurons in the ENS of the Porcine Descending Colon

    Directory of Open Access Journals (Sweden)

    Krystyna Makowska

    2017-03-01

    Full Text Available The enteric nervous system (ENS can undergo adaptive and reparative changes in response to physiological and pathological stimuli. These manifest primarily as alterations in the levels of active substances expressed by the enteric neuron. While it is known that mycotoxins can affect the function of the central and peripheral nervous systems, knowledge about their influence on the ENS is limited. Therefore, the aim of the present study was to investigate the influence of low doses of zearalenone (ZEN and T-2 toxin on calcitonin gene related peptide-like immunoreactive (CGRP-LI neurons in the ENS of the porcine descending colon using a double immunofluorescence technique. Both mycotoxins led to an increase in the percentage of CGRP-LI neurons in all types of enteric plexuses and changed the degree of co-localization of CGRP with other neuronal active substances, such as substance P, galanin, nitric oxide synthase, and cocaine- and amphetamine-regulated transcript peptide. The obtained results demonstrate that even low doses of ZEN and T-2 can affect living organisms and cause changes in the neurochemical profile of enteric neurons.

  9. Transcerebral exchange kinetics of nitrite and calcitonin gene-related peptide in acute mountain sickness: evidence against trigeminovascular activation?

    DEFF Research Database (Denmark)

    Bailey, Damian M; Taudorf, Sarah; Berg, Ronan M G;

    2009-01-01

    BACKGROUND AND PURPOSE: High-altitude headache is the primary symptom associated with acute mountain sickness, which may be caused by nitric oxide-mediated activation of the trigeminovascular system. Therefore, the present study examined the effects of inspiratory hypoxia on the transcerebral exc...

  10. 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

    , vasoactivity was manipulated by inhalation of oxygen. STUDY POPULATION AND METHODS: In 20 patients with alcoholic cirrhosis and 12 controls we determined COMP(art) (stroke volume relative to pulse pressure), cardiac output, plasma volume, systemic vascular resistance, central circulation time, plasma...... 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; p

  11. 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; Møller, Søren; 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...

  12. Immunohistochemical characterization of calcitonin gene-related peptide in the trigeminal system of the familial hemiplegic migraine 1 knock-in mouse.

    Science.gov (United States)

    Mathew, Rammya; Andreou, Anna P; Chami, Linda; Bergerot, Astrid; van den Maagdenberg, Arn Mjm; Ferrari, Michel D; Goadsby, Peter J

    2011-10-01

    Familial hemiplegic migraine type 1 (FHM-1) is caused by mutations in the CACNA1A gene, with the R192Q mutation being the most common. Elevated calcitonin gene-related peptide (CGRP) levels in acute migraine and clinical trials using CGRP receptor antagonists suggest CGRP-related mechanisms are important in migraine. Wild-type and R192Q knock-in mice were anaesthetized and perfused. Using immunohistochemical staining, the expression of CGRP in the trigeminocervical complex (TCC) and in the trigeminal and dorsal root ganglia was characterized. There was a 38% reduction in the percentage of CGRP-immunoreactive cells in the trigeminal ganglia (p migraine.

  13. Negative pressure for diabetic foot:Evaluation based on calcitonin gene-related peptide in the limb skin of dogs

    Institute of Scientific and Technical Information of China (English)

    Rui Ling; Jun Yi; Ling Wang; Mofan Ning

    2006-01-01

    BACKGROUND: Very good therapeutic effect has been obtained for limb negative pressure in treating limb ischemic diseases.But its mechanism in treating diabetic foot needs further investigation.OBJECTIVE:To observe the changes of calcitonin gene related peptide(CGRP)in sensory nerve fiber of skin of dogs with diabetic foot before and after limb negative pressure treatment,and make a comparison with normal dogs,then analyze the mechanism of limb negative pressure in treating diabetic foot.DESIGN:A randomized controlled animal experiment.SETTING:Third Department of General Surgery,Xijing Hospital,Fourth Military Medical University of Chinese PLA.MATERIALS:Fifteen healthy hybrid dogs,of either gender,weighing 12-18 kg,were provided by Animal Room,Xijing Hospital of the Fourth Military Medical University of Chinese PLA.After being numbered,the involved dogs were randomly assigned into 3 groups:treatment group,model group and normal control group,5 dogs each.Limb negative pressure therapeutic machine(self-made);Anti-CGRP serum (primary antibody,Watpa Company,England);rabbit anti-BigG(second antibody),ABC compound solution,DAB reagent,glucose oxidase reagent,Tdxon-X100 solution(Sigma company,USA),ammonium nickelous sulfate reagent(Xi'an Chemical Reagent Factory),neutral gum-solution(import,Shanghai Reagent Co.,Ltd.);Leitz1400 sliding freezing microtome(Leitz Company,Germany);Leica 1800 cryostat microtome(Leica Company,Germany);Quantimet570 image analyzer(Leica Company,Germany).METHODS:This experiment was carried out in the Animal Room,Xijing Hospital,Fourth Military Medical University of Chinese PLA from October 2005 to June 2006.①After the dogs in the treatment and model groups were anesthetized,their pancreatic tissues were removed completely and animal models of type I diabetes mellitus were developed.All the femoral artery branches including deep femoral artery were ligated and cut off.A helical wire was inserted into the distal femoral artery cavity for narrowing

  14. Calcitonin gene-related peptide in anterior and posterior horns of spinal cord after brachial plexus injury

    Institute of Scientific and Technical Information of China (English)

    Longju Chen; Peijun Wang; Feng Li; Wutian Wu

    2007-01-01

    BACKGROUND: The changes of calcitonin gene-related peptide (CGRP) expression are closely associated with peripheral nerve injury, whereas it should be further investigated whether the damage of central nerve can lead to the changes of CGRP expression, and whether it is associated with the neural regeneration and repair.OBJECTIVE: To observe the changing law of CGRP expression in the anterior and posterior horns of spinal cord following brachial plexus injury.DESIGN: A randomized controlled trial.SETTINGS: Department of Anatomy, Yunyang Medical College; Department of Anatomy, Basic Medical College, Sun Yat-sen University.MATERIALS: Sixty-five adult male SD rats of clean degree, weighing 180 - 220 g, provided by the experimental animal center of the Basic Medical College, Sun Yat-sen University, were randomly divided into control group (n =5) and experimental group (n =60), and the latter was subdivided into three damage groups: avulsion of anterior root group (n =20), disjunction of posterior root group (n =20) and transection of spinal cord group (n =20). Diaminobenzidine (DAB) chromogen, rabbit anti-CGRP polyclonal antibody were the products of Sigma Company; Leica image analytical apparatus was produced by QUIN Company (Germany); Histotome by Sigma Company.METHODS: The experiments were carried out in the Department of Anatomy, Basic Medical College, Sun Yat-sen University from September 2004 to March 2005. Three kinds of models of brachial plexus injury were established: In the avulsion of anterior root group, right C7 anterior root was avulsed, and the distal nerve residual root was transected. In the disjunction of posterior root group, right C7 anterior root was avulsed and right C5 - T1 posterior horns were cut to block the sensory afferent pathway. In the transection of spinal cord group, right C7 anterior root was avulsed and C5-6 segments of right spinal cord were semi-transected to block the cortical descending pathway. In the control group, C5 - T1

  15. Anti-nociceptive effects of calcitonin gene-related peptide in nucleus raphe magnus of rats: an effect attenuated by naloxone.

    Science.gov (United States)

    Huang, Y; Brodda-Jansen, G; Lundeberg, T; Yu, L C

    2000-08-04

    The present study investigated the role of calcitonin gene-related peptide (CGRP) on nociception in nucleus raphe magnus (NRM) and the interaction between CGRP and opioid peptides in NRM of rats. CGRP-like immunoreactivity was found at a concentration of 6.0+/-0. 77 pmol/g in NRM tissue of ten samples of rats, suggesting that it may contribute to physiological responses orchestrated by the NRM. The hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation increased significantly after intra-NRM administration of 0.5 or 1 nmol of CGRP in rats, but not 0.25 nmol. The anti-nociceptive effect induced by CGRP was antagonized by following intra-NRM injection of 1 nmol of the CGRP receptor antagonist CGRP8-37. Furthermore, the CGRP-induced anti-nociceptive effect was attenuated by following intra-NRM administration of 6 nmol of naloxone. The results indicate that CGRP and its receptors play an important role in anti-nociception, and there is a possible interaction between CGRP and opioid peptides in NRM of rats.

  16. Effects of rizatriptan on the expression of calcitonin gene-related peptide and cholecystokinin in the periaqueductal gray of a rat migraine model.

    Science.gov (United States)

    Yao, Gang; Han, Ximei; Hao, Tingting; Huang, Qian; Yu, Tingmin

    2015-02-05

    Triptans are serotonin 5-hydroxytryptamine receptor 1B/D agonists that are highly effective in the treatment of migraine. We previously found that rizatriptan can reduce the expression of proenkephalin and P substance in the rat midbrain, suggesting that rizatriptan may exert its analgesic effects by influencing the endogenous pain modulatory system. Calcitonin gene-related peptide (CGRP) and cholecystokinin (CCK) are mainly responsible for antagonizing the analgesic effects of opioid peptides in the endogenous pain modulatory system. In this study, we investigated the effects of rizatriptan on the expression of CGRP and CCK in the periaqueductal gray (PAG), a key structure of the endogenous pain modulatory system, in a rat migraine model induced by nitroglycerin. We found that the mRNA and protein levels of CGRP and CCK in the PAG of migraine rats were significantly increased compared to those in control rats, and these levels were significantly reduced upon treatment with rizatriptan in migraine rats (P<0.05). Our results suggest that the expression of CGRP and CCK in the endogenous pain modulatory system may be increased during migraine attacks, which further antagonizes the analgesic effects of endogenous opioid peptides and induces sustained migraine. Rizatriptan, however, significantly reduces the levels of CGRP and CCK to enhance the inhibition of pain signals via the endogenous pain modulatory system, resulting in effective treatment of migraine.

  17. 降钙素基因相关肽受体组分蛋白%Researches of calcitonin gene-related peptide receptor component protein

    Institute of Scientific and Technical Information of China (English)

    唐江琼; 秦旭平

    2011-01-01

    降钙素基因相关肽受体组分蛋白(calcitonin gene-related peptide-receptor component protein,CGRP-RCP)是降钙素基因相关肽受体的一个具有146/148个氨基酸的胞内膜周边蛋白,特异地与降钙素受体样受体(calcitonin receptor-like receptor,CRLR)相互作用并促进CGRP和肾上腺髓质素的信号跨膜转导,现认为CGRP-RCP也是G蛋白偶联受体中一个动态的调节器.CGRP-RCP的mRNA在人和鼠的几乎所有组织均可检测到,在小鼠睾丸中分布尤其明显.在哺乳动物中,CGRP-RCP与C17(酵母菌中聚合酶Ⅲ的必需亚基)是直系同源蛋白,人体的CGRP-RCP能取代酵母中的C17,发挥与Cl7相同的生物学作用.%Calcitonin gene-related peptide receptor component protein (CGRP-RCP), an additional accessory protein of the calcitonin gene-related peptide receptor and an intracellular peripheral membrane protein, is composed of 146-148 residues, which interacts specifically with the calcitonin receptor-like receptor (CRLR) and facilitates signal transduction by CGRP and adrenomedullin.Furthermore, CGRP-RCP is a dynamic regulator of G protein-coupled signal transduction, and implies an additional level of receptor regulation unique to the CGRP system. The CGRP-RCP mRNA is expressed in all tissues of the human and mice, especially more in the testis of mice. Moreover, CGRP-RCP is the mammalian orthologue of C 17 (an essential subunit of yeast RNA polymerase) and human RCP could functionally replace its orthologue in yeast.

  18. Effect of Chinese Herbal Fumigation Combined with Tuina on Vertigo and Concentrations of Endothelin and Calcitonin Gene-related Peptide in Patients with Vertebral Artery Cervical Spondylosis

    Institute of Scientific and Technical Information of China (English)

    Zhao Cheng-fei; Liu Xiao-an; Ding Yun

    2014-01-01

    Objective:To observe the effect of Chinese herbal fumigation combined with three-step tuina manipulation on concentration of endothelin (ET) and calcitonin gene-related peptide (CGRP) and vertigo in patients with vertebral artery cervical spondylosis (VACS). Methods:A total of 120 eligible cases were randomly allocated into an observation group and a control group, 60 in each group. Cases in the observation group were treated with Chinese herbal fumigation combined with three-step tuina manipulation, whereas cases in the control group were treated with oral Flunarizine Hydrochloride Capsules. Results: After treatment, vertigo in both groups was alleviated; there were intra-group significant differences in ET decrease and CGRP increase (P Conclusion: Chinese herbal fumigation combined with three-step tuina manipulation can regulate the levels of ET and CGRP and improve vertigo in patients with VACS. Its therapeutic efficacy is superior to oral Flunarizine Hydrochloride Capsules.

  19. Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine

    DEFF Research Database (Denmark)

    Dodick, David W; Goadsby, Peter J; Silberstein, Stephen D

    2014-01-01

    to treatment allocation during the study. The primary objective was to assess safety at 12 weeks after infusion. The primary efficacy endpoint was the change from baseline to weeks 5-8 in the frequency of migraine days, as recorded in patient electronic diaries. Patients were followed up until 24 weeks...... and one had one serious adverse event, and in the placebo group, one patient had one serious adverse event. There were no differences in vital signs or laboratory safety data between the two treatment groups. The mean change in migraine days between baseline and weeks 5-8 was -5·6 (SD 3·0) for the ALD403......BACKGROUND: Calcitonin gene-related peptide (CGRP) is crucial in the pathophysiology of migraine. We assessed the safety, tolerability, and efficacy of ALD403, a genetically engineered humanised anti-CGRP antibody, for migraine prevention. METHODS: In this randomised, double-blind, placebo...

  20. Calcitonin gene-related peptide in blood: is it increased in the external jugular vein during migraine and cluster headache? A review

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Le, Han

    2009-01-01

    The involvement of calcitonin gene-related peptide (CGRP) in migraine pathophysiological mechanisms is shown by the facts that CGRP can induce migraine and that two CGRP antagonists, olcegepant and telcagepant, are effective in the treatment of migraine attacks. Increase of the neuropeptide CGRP...... during migraine and cluster headache attacks in the extracerebral circulation as measured in the external jugular vein (EJV) has been regarded as an established fact. Then in 2005, a study, using the migraine patients as their own controls, showed; however, no changes of CGRP in EJV. For migraine...... there is thus some uncertainty as to whether CGRP is increased in all migraine patients and more research is needed. In contrast, there are three 'positive' studies in cluster headache in which both sumatriptan, O(2) and spontaneous resolution normalized CGRP. The source of an increase of CGRP in EJV is most...

  1. Do sensory calcitonin gene-related peptide nerve fibres in the rat pelvic plexus supply autonomic neurons projecting to the uterus and cervix?

    Science.gov (United States)

    Houdeau, E; Barranger, E; Rossano, B

    2002-10-25

    Sensory nerve fibres containing calcitonin gene-related peptide (CGRP) innervate neurons of the paracervical ganglion (PCG) in the female rat pelvic plexus. We have combined retrograde tracing with immunocytochemistry to investigate whether CGRP-immunoreactive (-IR) fibres supply neurons targeting the genital tract. Of the total neurons projecting to either the uterine horns or the cervix, 38 and 41% received CGRP-IR innervation, respectively. All these neurons displayed choline acetyltransferase-IR, thus are cholinergic. They were found throughout the PCG and other pelvic plexus ganglia, namely accessory ganglia (AG) and hypogastric plexus (HP). Pelvic nerve section showed that afferent fibres in these nerves provided most of the CGRP-IR fibres supplying uterine- or cervical-related neurons in the PCG/AG, none in HP. It is suggested that such sensory-motor network may provide a local pathway for reflex control of genital tract activity, acting through cholinergic nerve projections.

  2. Expression of calcitonin gene-related peptide-receptor component protein (CGRP-RCP) in human myometrium in differing physiological states and following misoprostol administration.

    Science.gov (United States)

    Goharkhay, Nina; Lu, Jing; Felix, Juan C; Wing, Deborah A

    2007-09-01

    Our objective was to assess relative expression levels of mRNA for calcitonin gene-related peptide-receptor component protein (CGRP-RCP) in human myometrium in various physiological states. Using semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), we analyzed myometrial samples from 46 women (10 menopausal, 10 nongravid premenopausal, 19 gravidae, and 7 premenopausal misoprostol-treated nongravid women) for the specific expression of CGRP-RCP mRNA. The expression of CGRP-RCP was significantly increased in gravid compared with nongravid myometrium ( P RCP expression were found among the other study groups. We concluded that the increased mRNA expression CGRP-RCP in gravid myometrium supports the possibility of involvement of CGRP in the control of myometrial contractility. Additional studies are necessary to evaluate the exact mechanism of action of CGRP and CGRP-RCP in human myometrium.

  3. Colocalization and shared distribution of endomorphins with substance P, calcitonin gene-related peptide, gamma-aminobutyric acid, and the mu opioid receptor.

    Science.gov (United States)

    Greenwell, Thomas N; Martin-Schild, Sheryl; Inglis, Fiona M; Zadina, James E

    2007-07-10

    The endomorphins are endogenous opioids with high affinity and selectivity for the mu opioid receptor (MOR, MOR-1, MOP). Endomorphin-1 (Tyr-Pro-Trp-Phe-NH(2); EM1) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH(2); EM2) have been localized to many regions of the central nervous system (CNS), including those that regulate antinociception, autonomic function, and reward. Colocalization or shared distribution (overlap) of two neurotransmitters, or a transmitter and its cognate receptor, may imply an interaction of these elements in the regulation of functions mediated in that region. For example, previous evidence of colocalization of EM2 with substance P (SP), calcitonin gene-related peptide (CGRP), and MOR in primary afferent neurons suggested an interaction of these peptides in pain modulation. We therefore investigated the colocalization of EM1 and EM2 with SP, CGRP, and MOR in other areas of the CNS. EM2 was colocalized with SP and CGRP in the nucleus of the solitary tract (NTS) and with SP, CGRP and MOR in the parabrachial nucleus. Several areas in which EM1 and EM2 showed extensive shared distributions, but no detectable colocalization with other signaling molecules, are also described.

  4. Loss of α-calcitonin gene-related peptide (αCGRP) reduces the efficacy of the Vestibulo-ocular Reflex (VOR).

    Science.gov (United States)

    Luebke, Anne E; Holt, Joseph C; Jordan, Paivi M; Wong, Yi Shan; Caldwell, Jillian S; Cullen, Kathleen E

    2014-07-30

    The neuroactive peptide calcitonin-gene related peptide (CGRP) is known to act at efferent synapses and their targets in hair cell organs, including the cochlea and lateral line. CGRP is also expressed in vestibular efferent neurons as well as a number of central vestibular neurons. Although CGRP-null (-/-) mice demonstrate a significant reduction in cochlear nerve sound-evoked activity compared with wild-type mice, it is unknown whether and how the loss of CGRP influence vestibular system function. Vestibular function was assessed by quantifying the vestibulo-ocular reflex (VOR) in alert mice. The loss of CGRP in (-/-) mice was associated with a reduction of the VOR gain of ≈50% without a concomitant change in phase. Using immunohistochemistry, we confirmed that, although CGRP staining was absent in the vestibular end-organs of null (-/-) mice, cholinergic staining appeared normal, suggesting that the overall gross development of vestibular efferent innervation was unaltered. We further confirmed that the observed deficit in vestibular function of null (-/-) mice was not the result of nontargeted effects at the level of the extraocular motor neurons and/or their innervation of extraocular muscles. Analysis of the relationship between vestibular quick phase amplitude and peak velocity revealed that extraocular motor function was unchanged, and immunohistochemistry revealed no abnormalities in motor endplates. Together, our findings show that the neurotransmitter CGRP plays a key role in ensuring VOR efficacy.

  5. Identification in the human central nervous system, pituitary, and thyroid of a novel calcitonin gene-related peptide, and partial amino acid sequence in the spinal cord.

    Science.gov (United States)

    Petermann, J B; Born, W; Chang, J Y; Fischer, J A

    1987-01-15

    Two human genes encoding precursors for two calcitonin gene-related peptides (CGRP) I (or alpha) and II (or beta) have been identified (Steenbergh, P. H., Höppener, J. W. M., Zandberg, J., Lips, C. J. M., and Jansz, H. S. (1985) FEBS Lett. 183, 403-407). The amino acid sequence of CGRP-I was obtained in medullary thyroid carcinoma extracts (Morris, H. R., Panico, M., Etienne, T., Tippins, J., Girgis, S. I., and MacIntyre, I. (1984) Nature 308, 746-748), but not in normal human tissues. The human CGRP-II peptide remained to be discovered. Here we have determined in the human spinal cord the amino acid composition and the partial amino acid sequence of the DNA-predicted CGRP-I and -II. The data indicate for the first time the existence of a second CGRP different from the known CGRP-I. CGRP-II has been identified in the central nervous system, pituitary, thyroid, and in medullary thyroid carcinoma as a major CGRP form together with CGRP-I.

  6. Calcitonin Gene-Related Peptide (Cgrp, Adrenomedullin (Am, Amylin, And Calcitonin (Ct Receptors And Overlapping Biological Actions

    Directory of Open Access Journals (Sweden)

    J.A. Fischer

    2001-01-01

    Full Text Available CGRP, AM, amylin, and CT have in common N-terminal 6-7 amino acid ring structures linked by disulfide bridges and amidated C-termini required for biological activity. For the related bioactive peptides, receptor-binding sites linked to cAMP stimulation and to a lesser extent to the phospholipase C signaling pathway have been identified in tissue specific manner. The highest density of CGRP receptors has been recognized in the cerebellum and the spinal cord. There photoaffinity-labeled N-glycosylated 60,000 and 54,000 Mr proteins are converted to 46,000 and 41,000 Mr components following endoglycosidase F/N-glycosidase F treatment. The same proteins were specifically labeled with [125I]-hCGRP-I(1-37 and -(8-37. Some cross-reaction between the CGRP receptor and AM was evident whereas amylin and CT were only recognized at over 10-7 M. A different AM receptor localized predominantly in the lung recognized CGRP at low, and amylin and calcitonin at equally high concentrations. CT receptor binding sites have been identified in osteoclasts and in the periventricular region of the brain. They cross-reacted with amylin at low concentrations and with CGRP and AM at over 10-7 M. Amylin receptor binding sites cross-reacting with salmon CT and CGRP but not with hCT and adrenomedullin to any great extent were originally described by Sexton in the nucleus accumbens and may represent a second CGRP receptor. The structure of a CT receptor was elucidated by the group of Goldring in 1991 through molecular cloning, and of a 60% homologous human CT receptor-like receptor (CRLR shortly thereafter here. The latter was an orphan receptor until the discovery of the receptor-activity-modifying proteins (RAMP by Foord which upon coexpression yield a CGRP receptor with RAMP1 and an AM receptor with RAMP2. Coexpression of the hCT receptor isotype 2 revealed a CGRP/amylin receptor with RAMP1 and an amylin receptor isotype with RAMP3. The CRLR/RAMP1 receptor antagonized by

  7. Conservation of capa peptide-induced nitric oxide signalling in Diptera.

    Science.gov (United States)

    Pollock, Valerie P; McGettigan, James; Cabrero, Pablo; Maudlin, Ian M; Dow, Julian A T; Davies, Shireen-A

    2004-11-01

    In D. melanogaster Malpighian (renal) tubules, the capa peptides stimulate production of nitric oxide (NO) and guanosine 3', 5'-cyclic monophosphate (cGMP), resulting in increased fluid transport. The roles of NO synthase (NOS), NO and cGMP in capa peptide signalling were tested in several other insect species of medical relevance within the Diptera (Aedes aegypti, Anopheles stephensi and Glossina morsitans) and in one orthopteran out-group, Schistocerca gregaria. NOS immunoreactivity was detectable by immunocytochemistry in tubules from all species studied. D. melanogaster, A. aegypti and A. stephensi express NOS in only principal cells, whereas G. morsitans and S. gregaria show more general NOS expression in the tubule. Measurement of associated NOS activity (NADPH diaphorase) shows that both D. melanogaster capa-1 and the two capa peptides encoded in the A. gambiae genome, QGLVPFPRVamide (AngCAPA-QGL) and GPTVGLFAFPRVamide (AngCAPA-GPT), all stimulate NOS activity in D. melanogaster, A. aegypti, A. stephensi and G. morsitans tubules but not in S. gregaria. Furthermore, capa-stimulated NOS activity in all the Diptera was inhibited by the NOS inhibitor l-NAME. All capa peptides stimulate an increase in cGMP content across the dipteran species, but not in the orthopteran S. gregaria. Similarly, all capa peptides tested stimulate fluid secretion in D. melanogaster, A. aegypti, A. stephensi and G. morsitans tubules but are either without effect or are inhibitory on S. gregaria. Consistent with these results, the Drosophila capa receptor was shown to be expressed in Drosophila tubules, and its closest Anopheles homologue was shown to be expressed in Anopheles tubules. Thus, we provide the first demonstration of physiological roles for two putative A. gambiae neuropeptides. We also demonstrate neuropeptide modulation of fluid secretion in tsetse tubule for the first time. Finally, we show the generality of capa peptide action, to stimulate NO/cGMP signalling and

  8. The potentiating effect of calcitonin gene-related peptide on transient receptor potential vanilloid-1 activity and the electrophysiological responses of rat trigeminal neurons to nociceptive stimuli.

    Science.gov (United States)

    Chatchaisak, Duangthip; Connor, Mark; Srikiatkhachorn, Anan; Chetsawang, Banthit

    2017-02-15

    Growing evidence suggests that calcitonin gene-related peptide (CGRP) participates in trigeminal nociceptive responses. However, the role of CGRP in sensitization or desensitization of nociceptive transduction remains poorly understood. In this study, we sought to further investigate the CGRP-induced up-regulation of transient receptor potential vanilloid-1 (TRPV1) and the responses of trigeminal neurons to nociceptive stimuli. Rat trigeminal ganglion (TG) organ cultures and isolated trigeminal neurons were incubated with CGRP. An increase in TRPV1 levels was observed in CGRP-incubated TG organ cultures. CGRP potentiated capsaicin-induced increase in phosphorylated CaMKII levels in the TG organ cultures. The incubation of the trigeminal neurons with CGRP significantly increased the inward currents in response to capsaicin challenge, and this effect was inhibited by co-incubation with the CGRP receptor antagonist, BIBN4068BS or the inhibitor of protein kinase A, H-89. These findings reveal that CGRP acting on trigeminal neurons may play a significant role in facilitating cellular events that contribute to the peripheral sensitization of the TG in nociceptive transmission.

  9. A research design for the quantification of the neuropeptides substance p and calcitonin gene-related Peptide in rat skin using Western blot analysis.

    Science.gov (United States)

    Lapin, Guilherme Abbud Franco; Hochman, Bernardo; Nishioka, Michele Akemi; Maximino, Jessica Ruivo; Chadi, Gerson; Ferreira, Lydia Masako

    2015-06-01

    To describe and standardize a protocol that overcomes the technical limitations of Western blot (WB) analysis in the quantification of the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) following nociceptive stimuli in rat skin. Male Wistar rats (Rattus norvegicus albinus) weighing 250 to 350 g were used in this study. Elements of WB analysis were adapted by using specific manipulation of samples, repeated cycles of freezing and thawing, more thorough maceration, and a more potent homogenizer; increasing lytic reagents; promoting greater inhibition of protease activity; and using polyvinylidene fluoride membranes as transfer means for skin-specific protein. Other changes were also made to adapt the WB analysis to a rat model. University research center. Western blot analysis adapted to a rat model. This research design has proven effective in collecting and preparing skin samples to quantify SP and CGRP using WB analysis in rat skin. This study described a research design that uses WB analysis as a reproducible, technically accessible, and cost-effective method for the quantification of SP and CGRP in rat skin that overcomes technical biases.

  10. Postnatal development of protein gene product 9.5 and calcitonin gene-related peptide immunoreactive nerve fibres in rat temporomandibular joint disc.

    Science.gov (United States)

    Ueki, N; Tanaka, E; Watanabe, M; Wakida, K; Takahashi, O; Uchida, T; Tanne, K

    2003-02-01

    Protein gene product 9.5 (PGP 9.5), an immunohistochemical marker of whole nerve fibres, and calcitonin gene-related peptide (CGRP), a marker of thin nerve fibres, were used to elucidate the postnatal development of nerve fibres in rat temporomandibular joint (TMJ) disc. At birth, PGP 9.5-immunoreactive nerve fibres exhibited running towards the central area of the disc, invading by approximately 95 m from the disc attachment. The nerve fibres existing inside the disc became longer during postnatal development. The number of nerve fibres in the disc increased in a progressive manner up to 40 days after birth. CGRP-immunoreactive nerve fibres also presented changes essentially similar to those of PGP 9.5-immunoreactive nerve fibres. However, the proportion of CGRP-immunoreactive nerve fibres to PGP 9.5-immunoreactive ones was approximately 80%, and remained constant up to 40 days after birth. In conclusion, the distribution and the number of nerve fibres are variable during postnatal development, although the ratio of thin nerve fibres remains invariable. It is emphasized that these changes of innervation in the TMJ are associated with the development of masticatory function.

  11. Tachykinins, calcitonin gene-related peptide and neuropeptide Y in nerves of the mammalian thymus: interactions with mast cells in autonomic and sensory neuroimmunomodulation?

    Science.gov (United States)

    Weihe, E; Müller, S; Fink, T; Zentel, H J

    1989-05-22

    By the use of light microscopic (LM) immunohistochemistry the distribution of tachykinin (TK)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivity in nerves supplying the mammalian (rat, mouse, guinea-pig, cat) thymus gland has been determined. There were no interspecies variations. Fibres staining for TK and CGRP completely overlapped indicating coexistence. They were present in the capsule, in interlobular septa and in the corticomedullary boundary and occurred in perivascular and paravascular plexus supplying arteries, veins and the microvasculature. Some TK/CGRP-immunoreactive (ir) fibres travelled between lymphoid cells and close contacts with mast cells were frequent. NPY-ir fibres were different from those staining for TK/CGRP and predominated in the perivascular plexus of arterial blood vessels. Only very rarely they coursed in the lymphoid parenchyma. Intimate contacts of NPY-ir fibres with mast cells were less frequent than those of TK/CGRP-ir fibres. We conclude that the NPY innervation is mainly sympathetic noradrenergic while thymic nerves coding for TK and CGRP are most likely of sensory origin. These pathways may play a differential neuroimmunomodulatory role in the thymus, possibly via interaction with mast cells.

  12. Developmental localization of calcitonin gene-related peptide in dorsal sensory axons and ventral motor neurons of mouse cervical spinal cord.

    Science.gov (United States)

    Kim, Jeongtae; Sunagawa, Masanobu; Kobayashi, Shiori; Shin, Taekyun; Takayama, Chitoshi

    2016-04-01

    Calcitonin gene-related peptide (CGRP) is a 37-amino-acid neuropeptide, synthesized by alternative splicing of calcitonin gene mRNA. CGRP is characteristically distributed in the nervous system, and its function varies depending on where it is expressed. To reveal developmental formation of the CGRP network and its function in neuronal maturation, we examined the immunohistochemical localization of CGRP in the developing mouse cervical spinal cord and dorsal root ganglion. CGRP immunolabeling (IL) was first detected in motor neurons on E13, and in ascending axons of the posterior funiculus and DRG neurons on E14. CGRP-positive sensory axon fibers entered Laminae I and II on E16, and Laminae I through IV on E18. The intensity of the CGRP-IL gradually increased in both ventral and dorsal horns during embryonic development, but markedly decreased in the ventral horn after birth. These results suggest that CGRP is expressed several days after neuronal settling and entry of sensory fibers, and that the CGRP network is formed in chronological and sequential order. Furthermore, because CGRP is markedly expressed in motor neurons when axons are vastly extending and innervating targets, CGRP may also be involved in axonal elongation and synapse formation during normal development.

  13. Antimicrobial peptides and nitric oxide production by neutrophils from periodontitis subjects.

    Science.gov (United States)

    Mariano, F S; Campanelli, A P; Nociti Jr, F H; Mattos-Graner, R O; Gonçalves, R B

    2012-11-01

    Neutrophils play an important role in periodontitis by producing nitric oxide (NO) and antimicrobial peptides, molecules with microbicidal activity via oxygen-dependent and -independent mechanisms, respectively. It is unknown whether variation in the production of antimicrobial peptides such as LL-37, human neutrophil peptides (HNP) 1-3, and NO by neutrophils influences the pathogenesis of periodontal diseases. We compared the production of these peptides and NO by lipopolysaccharide (LPS)-stimulated neutrophils isolated from healthy subjects and from patients with periodontitis. Peripheral blood neutrophils were cultured with or without Aggregatibacter actinomycetemcomitans-LPS (Aa-LPS), Porphyromonas gingivalis-LPS (Pg-LPS) and Escherichia coli-LPS (Ec-LPS). qRT-PCR was used to determine quantities of HNP 1-3 and LL-37 mRNA in neutrophils. Amounts of HNP 1-3 and LL-37 proteins in the cell culture supernatants were also determined by ELISA. In addition, NO levels in neutrophil culture supernatants were quantitated by the Griess reaction. Neutrophils from periodontitis patients cultured with Aa-LPS, Pg-LPS and Ec-LPS expressed higher HNP 1-3 mRNA than neutrophils from healthy subjects. LL-37 mRNA expression was higher in neutrophils from patients stimulated with Aa-LPS. Neutrophils from periodontitis patients produced significantly higher LL-37 protein levels than neutrophils from healthy subjects when stimulated with Pg-LPS and Ec-LPS, but no difference was observed in HNP 1-3 production. Neutrophils from periodontitis patients cultured or not with Pg-LPS and Ec-LPS produced significantly lower NO levels than neutrophils from healthy subjects. The significant differences in the production of LL-37 and NO between neutrophils from healthy and periodontitis subjects indicate that production of these molecules might influence individual susceptibility to important periodontal pathogens.

  14. Antimicrobial peptides and nitric oxide production by neutrophils from periodontitis subjects

    Directory of Open Access Journals (Sweden)

    F.S. Mariano

    2012-11-01

    Full Text Available Neutrophils play an important role in periodontitis by producing nitric oxide (NO and antimicrobial peptides, molecules with microbicidal activity via oxygen-dependent and -independent mechanisms, respectively. It is unknown whether variation in the production of antimicrobial peptides such as LL-37, human neutrophil peptides (HNP 1-3, and NO by neutrophils influences the pathogenesis of periodontal diseases. We compared the production of these peptides and NO by lipopolysaccharide (LPS-stimulated neutrophils isolated from healthy subjects and from patients with periodontitis. Peripheral blood neutrophils were cultured with or without Aggregatibacter actinomycetemcomitans-LPS (Aa-LPS, Porphyromonas gingivalis-LPS (Pg-LPS and Escherichia coli-LPS (Ec-LPS. qRT-PCR was used to determine quantities of HNP 1-3 and LL-37 mRNA in neutrophils. Amounts of HNP 1-3 and LL-37 proteins in the cell culture supernatants were also determined by ELISA. In addition, NO levels in neutrophil culture supernatants were quantitated by the Griess reaction. Neutrophils from periodontitis patients cultured with Aa-LPS, Pg-LPS and Ec-LPS expressed higher HNP 1-3 mRNA than neutrophils from healthy subjects. LL-37 mRNA expression was higher in neutrophils from patients stimulated with Aa-LPS. Neutrophils from periodontitis patients produced significantly higher LL-37 protein levels than neutrophils from healthy subjects when stimulated with Pg-LPS and Ec-LPS, but no difference was observed in HNP 1-3 production. Neutrophils from periodontitis patients cultured or not with Pg-LPS and Ec-LPS produced significantly lower NO levels than neutrophils from healthy subjects. The significant differences in the production of LL-37 and NO between neutrophils from healthy and periodontitis subjects indicate that production of these molecules might influence individual susceptibility to important periodontal pathogens.

  15. Effects of Qindan Capsule(芩丹胶囊) on Blood Pressure,Endothelin, Calcitonin Gene-related Peptide and Angiotensin-Ⅱ in Spontaneous Hypertensive Rats

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To observe the hypotensive effects of Qindan Capsule (芩丹胶囊, QC) on spontaneous hypertensive rats (SHR) and its effect on the contents of endothelin (ET), calcitonin gene-related peptide (CGRP) and angiotensin-Ⅱ (Ang-Ⅱ ) in plasma and vascular tissues, and to investigate the possible mechanism of QC in lowering blood pressure. Methods: Forty SHRs were divided into 5 groups: the high dosage QC group [QCHD, 750 mg/(kg·d)], the low dosage QC group [QCLD, 150 mg/(kg·d)], the Niuhuang Jiangya Pill group [牛黄降压丸, NJP, 200 mg/(kg·d)], the Captopril group [ 15 mg/(kg·d)]and the model group, 8 in each group. Meanwhile, a normal control group consisting of 8 Wistar-Kyoto (WKY) rats was set up also. All the rats were administered with medicine through gastrogavage. Systolic blood pressure (SBP),level of ET, CGRP and Ang-Ⅱ in plasma and Ang-Ⅱ in tissues of mesenteric artery were detected in all the rats after 12 weeks of treatment. Results: The level of SBP after treatment in the QCHD group was lower than that in the model group ( P<0.01 ), but with no significant difference as compared with that in the Captopril group and the NJP group (P>0.05). After treatment, the plasma level of ET was lower and CGRP higher than those in the model group (both P<0.05), and also higher than those in the NJP and Captopril group (both P<0.05). As for the content of Ang- Ⅱ, in mesenteric arterial tissues, it was lower in the QCHD group than that in the model group ( P<0.05), but in plasma, it showed no significant difference between the two groups (P>0.05). Conclusion: QC has a satisfactory hypotensive action on SHR rats, and its mechanism may be associated with the regulation on plasma vasoactive peptide and regional renin-angiotensin system.

  16. A Novel α-Calcitonin Gene-Related Peptide Analogue Protects Against End-Organ Damage in Experimental Hypertension, Cardiac Hypertrophy, and Heart Failure.

    Science.gov (United States)

    Aubdool, Aisah A; Thakore, Pratish; Argunhan, Fulye; Smillie, Sarah-Jane; Schnelle, Moritz; Srivastava, Salil; Alawi, Khadija M; Wilde, Elena; Mitchell, Jennifer; Farrell-Dillon, Keith; Richards, Daniel A; Maltese, Giuseppe; Siow, Richard C; Nandi, Manasi; Clark, James E; Shah, Ajay M; Sams, Anette; Brain, Susan D

    2017-07-25

    Research into the therapeutic potential of α-calcitonin gene-related peptide (α-CGRP) has been limited because of its peptide nature and short half-life. Here, we evaluate whether a novel potent and long-lasting (t½ ≥7 hours) acylated α-CGRP analogue (αAnalogue) could alleviate and reverse cardiovascular disease in 2 distinct murine models of hypertension and heart failure in vivo. The ability of the αAnalogue to act selectively via the CGRP pathway was shown in skin by using a CGRP receptor antagonist. The effect of the αAnalogue on angiotensin II-induced hypertension was investigated over 14 days. Blood pressure was measured by radiotelemetry. The ability of the αAnalogue to modulate heart failure was studied in an abdominal aortic constriction model of murine cardiac hypertrophy and heart failure over 5 weeks. Extensive ex vivo analysis was performed via RNA analysis, Western blot, and histology. The angiotensin II-induced hypertension was attenuated by cotreatment with the αAnalogue (50 nmol·kg(-1)·d(-1), SC, at a dose selected for lack of long-term hypotensive effects at baseline). The αAnalogue protected against vascular, renal, and cardiac dysfunction, characterized by reduced hypertrophy and biomarkers of fibrosis, remodeling, inflammation, and oxidative stress. In a separate study, the αAnalogue reversed angiotensin II-induced hypertension and associated vascular and cardiac damage. The αAnalogue was effective over 5 weeks in a murine model of cardiac hypertrophy and heart failure. It preserved heart function, assessed by echocardiography, while protecting against adverse cardiac remodeling and apoptosis. Moreover, treatment with the αAnalogue was well tolerated with neither signs of desensitization nor behavioral changes. These findings, in 2 distinct models, provide the first evidence for the therapeutic potential of a stabilized αAnalogue, by mediating (1) antihypertensive effects, (2) attenuating cardiac remodeling, and (3) increasing

  17. Effects of tegaserod on Fos,substance P and calcitonin gene-related peptide expression induced by colon inflammation in lumbarsacral spinal cord

    Institute of Scientific and Technical Information of China (English)

    Yi-Ning Sun; Jin-Yan Luo

    2004-01-01

    AIM: To investigate the mechanisms of tegaserod, a partial 5-HT4 agonist, in reducing visceral sensitivity by observing Fos, substance P (SP) and calcitonin gene-related peptide (CGRP) expression in the lumbarsacral spinal cord inducedby colonic inflammation in rats.METHODS: Twenty-four male rats with colonic inflammation induced by intraluminal instillation of trinitrobenzenesulfonic acid (TNBS) were divided into 3 groups. Treatment group Treatment group 2: intra-gastric administration of tegaserod,saline, 2.0 mL/d. After 7 d of intra-gastric administration,lumbarsacral spinal cord was removed and processed for Fos, SP and CGRP immunohistochemistry.RESULTS: In rats of the control group, the majority of Fos labeled neurons was localized in deeper laminae of the lumbarsacral spinal cord (L5-S1). SP and CGRP were primarily expressed in the superficial laminae of the spinal cord after TNBS injection. Intra-gastric administration of tegaserod neurons (22.0±7.7) and SP density (12.5±1.4) in the dorsal horn in the lumbarsacral spinal cord compared to those of the control group (62.2±18.9, 35.9±8.9, P<0.05). However,CGRP content in dorsal horn did not significantly reduce in rats of treatment group 1 (1.2±1.1) compared to that of the control group (2.8±2.4, P>0.05). Neither Fos expression nor SP or CGRP density in the dorsal horn significantly declined in rats of treatment group 2 compared to those of the control group (P>0.05).CONCLUSION: Tegaserod can significantly reduce Fos labeled neurons in the lumbarsacral spinal cord induced by colonic inflammation. Tegaserod may reduce visceral sensitivity by inhibiting SP expression in the dorsal horn of spinal cord.

  18. Mitogen-activated protein kinase pathways are involved in the upregulation of calcitonin gene-related peptide of rat trigeminal ganglion after organ culture.

    Science.gov (United States)

    Lei, Li; Yuan, Xingyun; Wang, Shaolan; Zhang, Fujun; Han, Yan; Ning, Qilan; Luo, Guogang; Lu, Shemin

    2012-09-01

    The trigeminal ganglion (TG) can express and release calcitonin gene-related peptide (CGRP), an important neuropeptide that plays a crucial role in migraine attack and cluster headache. Activation of rat TG increases CGRP expression. However, the regulatory mechanism of CGRP expression in TG neurons remains to be explored. This study aims to evaluate the involvement of mitogen-activated protein kinase (MAPK) pathways in CGRP upregulation after rat TG organ culture. Rat TG was cultured alone for 24 h or cultured in combination with MAPK inhibitors, tumor necrosis factor α (TNF-α), or interleukin 1β (IL-1β) for 24 h. CGRP protein was determined using immunohistochemistry. The mRNA levels of CGRP, TNF-α, and IL-1β were analyzed through real-time quantitative polymerase chain reaction. MAPK phosphorylation was detected via western blot. After rat TG organ culture, the expressions of CGRP, TNF-α, and IL-1β were upregulated at 24 h. The phosphorylation of extracellular signal-regulated kinases (ERK1/2), P38, and c-jun N-terminal kinases (JNK) significantly increased at 30 min compared with fresh rat TG. In addition, both CGRP expression and phosphorylation of ERK1/2, P38, and JNK were enhanced obviously after rat TG treatment with TNF-α or IL-1β compared with fresh rat TG. However, they decreased markedly after rat TG pretreatment with PD98059 (ERK1/2 inhibitor), SB203580 (P38 inhibitor), or SP600125 (JNK inhibitor) compared with rat TG co-culture with TNF-α or IL-1β. In conclusion, the elevated CGRP expression after rat TG organ culture can be regulated via MAPK pathways. The findings provide insight into the molecular mechanisms and experimental evidence for therapeutic targets of migraine.

  19. Phenotypic alterations of neuropeptide Y and calcitonin gene-related peptide-containing neurons innervating the rat temporomandibular joint during carrageenan-induced arthritis

    Science.gov (United States)

    Damico, J.P.; Ervolino, E.; Torres, K.R.; Batagello, D.S.; Cruz-Rizzolo, R.J.; Casatti, C.A.; Bauer, J.A.

    2012-01-01

    The aim of this study was to identify immunoreactive neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) neurons in the autonomic and sensory ganglia, specifically neurons that innervate the rat temporomandibular joint (TMJ). A possible variation between the percentages of these neurons in acute and chronic phases of carrageenan-induced arthritis was examined. Retrograde neuronal tracing was combined with indirect immunofluorescence to identify NPY-immunoreactive (NPY-IR) and CGRP- immunoreactive (CGRP-IR) neurons that send nerve fibers to the normal and arthritic temporomandibular joint. In normal joints, NPY-IR neurons constitute 78±3%, 77±6% and 10±4% of double-labeled nucleated neuronal profile originated from the superior cervical, stellate and otic ganglia, respectively. These percentages in the sympathetic ganglia were significantly decreased in acute (58±2% for superior cervical ganglion and 58±8% for stellate ganglion) and chronic (60±2% for superior cervical ganglion and 59±15% for stellate ganglion) phases of arthritis, while in the otic ganglion these percentages were significantly increased to 19±5% and 13±3%, respectively. In the trigeminal ganglion, CGRP-IR neurons innervating the joint significantly increased from 31±3% in normal animals to 54±2% and 49±3% in the acute and chronic phases of arthritis, respectively. It can be concluded that NPY neurons that send nerve fibers to the rat temporomandibular joint are located mainly in the superior cervical, stellate and otic ganglia. Acute and chronic phases of carrageenan-induced arthritis lead to an increase in the percentage of NPY-IR parasympathetic and CGRP-IR sensory neurons and to a decrease in the percentage of NPY-IR sympathetic neurons related to TMJ innervation. PMID:23027347

  20. Phenotypic alterations of neuropeptide Y and calcitonin gene-related peptide-containing neurons innervating the rat temporomandibular joint during carrageenan-induced arthritis

    Directory of Open Access Journals (Sweden)

    J.P. Damico

    2012-10-01

    Full Text Available The aim of this study was to identify immunoreactive neuropeptide Y (NPY and calcitonin gene-related peptide (CGRP neurons in the autonomic and sensory ganglia, specifically neurons that innervate the rat temporomandibular joint (TMJ. A possible variation between the percentages of these neurons in acute and chronic phases of carrageenan-induced arthritis was examined. Retrograde neuronal tracing was combined with indirect immunofluorescence to identify NPY-immunoreactive (NPY-IR and CGRP- immunoreactive (CGRP-IR neurons that send nerve fibers to the normal and arthritic temporomandibular joint. In normal joints, NPY-IR neurons constitute 78±3%, 77±6% and 10±4% of double-labeled nucleated neuronal profile originated from the superior cervical, stellate and otic ganglia, respectively. These percentages in the autonomic ganglia were significantly decreased in acute (58±2% to superior cervical ganglion and 58±8% to stellate ganglion and chronic (60±2% to superior cervical ganglion and 59±15% to stellate ganglion phases of arthritis, while in the otic ganglion these percentages were significantly increased to 19±5% and 13±3%, respectively. In the trigeminal ganglion, CGRP-IR neurons innervating the joint significantly increased from 31±3% in normal animals to 54±2% and 49±3% in the acute and chronic phases of arthritis, respectively. It can be concluded that NPY neurons that send nerve fibers to the rat temporomandibular joint are located mainly in the superior cervical, stellate and otic ganglia. Acute and chronic phases of carrageenan-induced arthritis lead to an increase in the percentage of NPY-IR parasympathetic and CGRP-IR sensory neurons and decrease in the percentage of NPY-IR sympathetic neurons related to TMJ innervation.

  1. Calcitonin gene-related peptide promotes the expression of osteoblastic genes and activates the WNT signal transduction pathway in bone marrow stromal stem cells

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    ZHOU, RI; YUAN, ZHI; LIU, JIERONG; LIU, JIAN

    2016-01-01

    Calcitonin gene-related peptide (CGRP) is known to induce osteoblastic differentiation and alkaline phosphatase activity in bone marrow stromal stem cells (BMSCs). However, it has remained elusive whether this effect is mediated by CGRP receptors directly or whether other signaling pathways are involved. The present study assessed the possible involvement of the Wnt/β-catenin signaling pathway in the activation of CGRP signaling during the differentiation of BMSCs. First, the differentiation of BMSCs was induced in vitro and the expression of CGRP receptors was examined by western blot analysis. The effects of exogenous CGRP and LiCl, a stimulator of the Wnt/β-catenin signaling pathway, on the osteoblastic differentiation of BMSCs were assessed; furthermore, the expression of mRNA and proteins involved in the Wnt/β-catenin signaling pathway was assessed using quantitative PCR and western blot analyses. The results revealed that CGRP receptors were expressed throughout the differentiation of BMSCs, at days 7 and 14. Incubation with CGRP and LiCl led to the upregulation of the expression of osteoblastic genes associated with the Wnt/β-catenin pathway, including the mRNA of c-myc, cyclin D1, Lef1, Tcf7 and β-catenin as well as β-catenin protein. However, the upregulation of these genes and β-catenin protein was inhibited by CGRP receptor antagonist or secreted frizzled-related protein, an antagonist of the Wnt/β-catenin pathway. The results of the present study therefore suggested that the Wnt/β-catenin signaling pathway may be involved in CGRP- and LiCl-promoted osteoblastic differentiation of BMSCs. PMID:27082317

  2. Somatostatin, substance P and calcitonin gene-related peptide-positive intramural nerve structures of the human large intestine affected by carcinoma.

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    Jerzy Kaleczyc

    2010-11-01

    Full Text Available The aim of this study was to investigate the arrangement and chemical coding of enteric nerve structures in the human large intestine affected by cancer. Tissue samples comprising all layers of the intestinal wall were collected during surgery form both morphologically unchanged and pathologically altered segments of the intestine (n=15, and fixed by immersion in buffered paraformaldehyde solution. The cryostat sections were processed for double-labelling immunofluorescence to study the distribution of the intramural nerve structures (visualized with antibodies against protein gene-product 9.5 and their chemical coding using antibodies against somatostatin (SOM, substance P (SP and calcitonin gene-related peptide (CGRP. The microscopic observations revealed distinct morphological differences in the enteric nerve system structure between the region adjacent to the cancer invaded area and the intact part of the intestine. In general, infiltration of the cancer tissue resulted in the gradual (depending on the grade of invasion first decomposition and reduction to final partial or complete destruction and absence of the neuronal elements. A comparative analysis of immunohistochemically labeled sections (from the unchanged and pathologically altered areas revealed a statistically significant decrease in the number of CGRP-positive neurons and nerve fibres in both submucous and myenteric plexuses in the transitional zone between morphologically unchanged and cancer-invaded areas. In this zone, a decrease was also observed in the density of SP-positive nerve fibres in all intramural plexuses. Conversely, the investigations demonstrated statistically insignificant differences in number of SP- and SOM-positive neurons and a similar density of SOM-positive nerve fibres in the plexuses of the intact and pathologically changed areas. The differentiation between the potential adaptive changes in ENS or destruction of its elements by cancer invasion should be

  3. Activation of calcitonin gene-related peptide signaling through the prostaglandin E2-EP1/EP2/EP4 receptor pathway in synovium of knee osteoarthritis patients.

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    Minatani, Atsushi; Uchida, Kentaro; Inoue, Gen; Takano, Shotaro; Aikawa, Jun; Miyagi, Masayuki; Fujimaki, Hisako; Iwase, Dai; Onuma, Kenji; Matsumoto, Toshihide; Takaso, Masashi

    2016-10-17

    Calcitonin gene-related peptide (CGRP) is a 37-amino-acid vasodilatory neuropeptide that binds to receptor activity-modifying protein 1 (RAMP1) and the calcitonin receptor-like receptor (CLR). Clinical and preclinical evidence suggests that CGRP is associated with hip and knee joint pain; however, the regulation mechanisms of CGRP/CGRP receptor signaling in synovial tissue are not fully understood. Synovial tissues were harvested from 43 participants with radiographic knee osteoarthritis (OA; unilateral Kellgren/Lawrence (K/L) grades 3-4) during total knee arthroplasty. Correlationships between the mRNA expression levels of CGRP and those of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and cycloxygenase-2 (COX-2) were evaluated using real-time PCR analysis of total RNA extracted from the collected synovial tissues. To investigate the factors controlling the regulation of CGRP and CGRP receptor expression, cultured synovial cells were stimulated with TNF-α, IL-1β, IL-6, and prostaglandin E2 (PGE2) and were also treated with PGE2 receptor (EP) agonist. CGRP and COX-2 localized in the synovial lining layer. Expression of COX-2 positively correlated with CGRP mRNA expression in the synovial tissue of OA patients. The gene expression of CGRP and RAMP1 increased significantly in synovial cells exogenously treated with PGE2 compared to untreated control cells. In cultured synovial cells, CGRP gene expression increased significantly following EP4 agonist treatment, whereas RAMP1 gene expression increased significantly in the presence of exogenously added EP1 and EP2 agonists. PGE2 appears to regulate CGRP/CGRP receptor signaling through the EP receptor in the synovium of knee OA patients.

  4. Changes in the Expressions of Iba1 and Calcitonin Gene-Related Peptide in Adjacent Lumbar Spinal Segments after Lumbar Disc Herniation in a Rat Model.

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    Cho, Hee Kyung; Ahn, Sang Ho; Kim, So-Yeon; Choi, Mi-Jung; Hwang, Se Jin; Cho, Yun Woo

    2015-12-01

    Lumbar disc herniation is commonly encountered in clinical practice and can induce sciatica due to mechanical and/or chemical irritation and the release of proinflammatory cytokines. However, symptoms are not confined to the affected spinal cord segment. The purpose of this study was to determine whether multisegmental molecular changes exist between adjacent lumbar spinal segments using a rat model of lumbar disc herniation. Twenty-nine male Sprague-Dawley rats were randomly assigned to either a sham-operated group (n=10) or a nucleus pulposus (NP)-exposed group (n=19). Rats in the NP-exposed group were further subdivided into a significant pain subgroup (n=12) and a no significant pain subgroup (n=7) using mechanical pain thresholds determined von Frey filaments. Immunohistochemical stainings of microglia (ionized calcium-binding adapter molecule 1; Iba1), astrocytes (glial fibrillary acidic protein; GFAP), calcitonin gene-related peptide (CGRP), and transient receptor potential vanilloid 1 (TRPV1) was performed in spinal dorsal horns and dorsal root ganglions (DRGs) at 10 days after surgery. It was found immunoreactivity for Iba1-positive microglia was higher in the L5 (P=0.004) dorsal horn and in the ipsilateral L4 (P=0.009), L6 (P=0.002), and S1 (P=0.002) dorsal horns in the NP-exposed group than in the sham-operated group. The expression of CGRP was also significantly higher in ipsilateral L3, L4, L6, and S1 segments and in L5 DRGs at 10 days after surgery in the NP-exposed group than in the sham-operated group (Plumbar disc herniation upregulates microglial activity and CGRP expression in many adjacent and ipsilateral lumbar spinal segments.

  5. Impact of Food Components on in vitro Calcitonin Gene-Related Peptide Secretion—A Potential Mechanism for Dietary Influence on Migraine

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    Margaret Slavin

    2016-07-01

    Full Text Available Calcitonin gene-related peptide (CGRP is a pivotal messenger in the inflammatory process in migraine. Limited evidence indicates that diet impacts circulating levels of CGRP, suggesting that certain elements in the diet may influence migraine outcomes. Interruption of calcium signaling, a mechanism which can trigger CGRP release, has been suggested as one potential route by which exogenous food substances may impact CGRP secretion. The objective of this study was to investigate the effects of foods and a dietary supplement on two migraine-related mechanisms in vitro: CGRP secretion from neuroendocrine CA77 cells, and calcium uptake by differentiated PC12 cells. Ginger and grape pomace extracts were selected for their anecdotal connections to reducing or promoting migraine. S-petasin was selected as a suspected active constituent of butterbur extract, the migraine prophylactic dietary supplement. Results showed a statistically significant decrease in stimulated CGRP secretion from CA77 cells following treatment with ginger (0.2 mg dry ginger equivalent/mL and two doses of grape pomace (0.25 and 1.0 mg dry pomace equivalent/mL extracts. Relative to vehicle control, CGRP secretion decreased by 22%, 43%, and 87%, respectively. S-petasin at 1.0 μM also decreased CGRP secretion by 24%. Meanwhile, S-petasin and ginger extract showed inhibition of calcium influx, whereas grape pomace had no effect on calcium. These results suggest that grape pomace and ginger extracts, and S-petasin may have anti-inflammatory propensity by preventing CGRP release in migraine, although potentially by different mechanisms, which future studies may elucidate further.

  6. A potent and selective calcitonin gene-related peptide (CGRP) receptor antagonist, MK-8825, inhibits responses to nociceptive trigeminal activation: Role of CGRP in orofacial pain.

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    Romero-Reyes, Marcela; Pardi, Vanessa; Akerman, Simon

    2015-09-01

    Temporomandibular disorders (TMDs) are orofacial pains within the trigeminal distribution, which involve the masticatory musculature, the temporomandibular joint or both. Their pathophysiology remains unclear, as inflammatory mediators are thought to be involved, and clinically TMD presents pain and sometimes limitation of function, but often appears without gross indications of local inflammation, such as visible edema, redness and increase in temperature. Calcitonin gene-related peptide (CGRP) has been implicated in other pain disorders with trigeminal distribution, such as migraine, of which TMD shares a significant co-morbidity. CGRP causes activation and sensitization of trigeminal primary afferent neurons, independent of any inflammatory mechanisms, and thus may also be involved in TMD. Here we used a small molecule, selective CGRP receptor antagonist, MK-8825, to dissect the role of CGRP in inducing spontaneous nociceptive facial grooming behaviors, neuronal activation in the trigeminal nucleus, and systemic release of pro-inflammatory cytokines, in a mouse model of acute orofacial masseteric muscle pain that we have developed, as a surrogate of acute TMD. We show that CFA masseteric injection causes significant spontaneous orofacial pain behaviors, neuronal activation in the trigeminal nucleus, and release of interleukin-6 (IL-6). In mice pre-treated with MK-8825 there is a significant reduction in these spontaneous orofacial pain behaviors. Also, at 2 and 24h after CFA injection the level of Fos immunoreactivity in the trigeminal nucleus, used as a marker of neuronal activation, was much lower on both ipsilateral and contralateral sides after pre-treatment with MK-8825. There was no effect of MK-8825 on the release of IL-6. These data suggest that CGRP may be involved in TMD pathophysiology, but not via inflammatory mechanisms, at least in the acute stage. Furthermore, CGRP receptor antagonists may have therapeutic efficacy in the treatment of TMD, as they

  7. Alpha-Calcitonin Gene-Related Peptide Can Reverse The Catabolic Influence Of UHMWPE Particles On RANKL Expression In Primary Human Osteoblasts

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    Max D. Kauther, Jie Xu, Christian Wedemeyer

    2010-01-01

    Full Text Available Background and purpose: A linkage between the neurotransmitter alpha-calcitonin gene-related peptide (alpha-CGRP and particle-induced osteolysis has been shown previously. The suggested osteoprotective influence of alpha-CGRP on the catabolic effects of ultra-high molecular weight polyethylene (UHMWPE particles is analyzed in this study in primary human osteoblasts. Methods: Primary human osteoblasts were stimulated by UHMWPE particles (cell/particle ratios 1:100 and 1:500 and different doses of alpha-CGRP (10-7 M, 10-9 M, 10-11 M. Receptor activator of nuclear factor-κB ligand (RANKL and osteoprotegerin (OPG mRNA expression and protein levels were measured by RT-PCR and Western blot. Results: Particle stimulation leads to a significant dose-dependent increase of RANKL mRNA in both cell-particle ratios and a significant down-regulation of OPG mRNA in cell-particle concentrations of 1:500. A significant depression of alkaline phosphatase was found due to particle stimulation. Alpha-CGRP in all tested concentrations showed a significant depressive effect on the expression of RANKL mRNA in primary human osteoblasts under particle stimulation. Comparable reactions of RANKL protein levels due to particles and alpha-CGRP were found by Western blot analysis. In cell-particle ratios of 1:100 after 24 hours the osteoprotective influence of alpha-CGRP reversed the catabolic effects of particles on the RANKL expression. Interpretation: The in-vivo use of alpha-CGRP, which leads to down-regulated RANKL in-vitro, might inhibit the catabolic effect of particles in conditions of particle induced osteolysis.

  8. An ongoing role of α-calcitonin gene-related peptide as part of a protective network against hypertension, vascular hypertrophy, and oxidative stress.

    Science.gov (United States)

    Smillie, Sarah-Jane; King, Ross; Kodji, Xenia; Outzen, Emilie; Pozsgai, Gabor; Fernandes, Elizabeth; Marshall, Nichola; de Winter, Patricia; Heads, Richard J; Dessapt-Baradez, Cecile; Gnudi, Luigi; Sams, Anette; Shah, Ajay M; Siow, Richard C; Brain, Susan D

    2014-05-01

    α-Calcitonin gene-related peptide (αCGRP) is a vasodilator, but there is limited knowledge of its long-term cardiovascular protective influence. We hypothesized that αCGRP protects against the onset and development of angiotensin II-induced hypertension and have identified protective mechanisms at the vascular level. Wild-type and αCGRP knockout mice that have similar baseline blood pressure were investigated in the angiotensin II hypertension model for 14 and 28 days. αCGRP knockout mice exhibited enhanced hypertension and aortic hypertrophy. αCGRP gene expression was increased in dorsal root ganglia and at the conduit and resistance vessel level of wild-type mice at both time points. βCGRP gene expression was also observed and shown to be linked to plasma levels of CGRP. Mesenteric artery contractile and relaxant responses in vitro and endothelial NO synthase expression were similar in all groups. The aorta exhibited vascular hypertrophy, increased collagen formation, and oxidant stress markers in response to angiotensin II, with highest effects observed in αCGRP knockout mice. Gene and protein expression of endothelial NO synthase was lacking in the aortae after angiotensin II treatment, especially in αCGRP knockout mice. These results demonstrate the ongoing upregulation of αCGRP at the levels of both conduit and resistance vessels in vascular tissue in a model of hypertension and the direct association of this with protection against aortic vascular hypertrophy and fibrosis. This upregulation is maintained at a time when expression of aortic endothelial NO synthase and antioxidant defense genes have subsided, in keeping with the concept that the protective influence of αCGRP in hypertension may have been previously underestimated.

  9. Nitric Oxide Contributes to Cadmium Toxicity in Arabidopsis by Promoting Cadmium Accumulation in Roots and by Up-Regulating Genes Related to Iron Uptake1[W

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    Besson-Bard, Angélique; Gravot, Antoine; Richaud, Pierre; Auroy, Pascaline; Duc, Céline; Gaymard, Frédéric; Taconnat, Ludivine; Renou, Jean-Pierre; Pugin, Alain; Wendehenne, David

    2009-01-01

    Nitric oxide (NO) functions as a cell-signaling molecule in plants. In particular, a role for NO in the regulation of iron homeostasis and in the plant response to toxic metals has been proposed. Here, we investigated the synthesis and the role of NO in plants exposed to cadmium (Cd2+), a nonessential and toxic metal. We demonstrate that Cd2+ induces NO synthesis in roots and leaves of Arabidopsis (Arabidopsis thaliana) seedlings. This production, which is sensitive to NO synthase inhibitors, does not involve nitrate reductase and AtNOA1 but requires IRT1, encoding a major plasma membrane transporter for iron but also Cd2+. By analyzing the incidence of NO scavenging or inhibition of its synthesis during Cd2+ treatment, we demonstrated that NO contributes to Cd2+-triggered inhibition of root growth. To understand the mechanisms underlying this process, a microarray analysis was performed in order to identify NO-modulated root genes up- and down-regulated during Cd2+ treatment. Forty-three genes were identified encoding proteins related to iron homeostasis, proteolysis, nitrogen assimilation/metabolism, and root growth. These genes include IRT1. Investigation of the metal and ion contents in Cd2+-treated roots in which NO synthesis was impaired indicates that IRT1 up-regulation by NO was consistently correlated to NO's ability to promote Cd2+ accumulation in roots. This analysis also highlights that NO is responsible for Cd2+-induced inhibition of root Ca2+ accumulation. Taken together, our results suggest that NO contributes to Cd2+ toxicity by favoring Cd2+ versus Ca2+ uptake and by initiating a cellular pathway resembling those activated upon iron deprivation. PMID:19168643

  10. Nitric oxide contributes to cadmium toxicity in Arabidopsis by promoting cadmium accumulation in roots and by up-regulating genes related to iron uptake.

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    Besson-Bard, Angélique; Gravot, Antoine; Richaud, Pierre; Auroy, Pascaline; Duc, Céline; Gaymard, Frédéric; Taconnat, Ludivine; Renou, Jean-Pierre; Pugin, Alain; Wendehenne, David

    2009-03-01

    Nitric oxide (NO) functions as a cell-signaling molecule in plants. In particular, a role for NO in the regulation of iron homeostasis and in the plant response to toxic metals has been proposed. Here, we investigated the synthesis and the role of NO in plants exposed to cadmium (Cd(2+)), a nonessential and toxic metal. We demonstrate that Cd(2+) induces NO synthesis in roots and leaves of Arabidopsis (Arabidopsis thaliana) seedlings. This production, which is sensitive to NO synthase inhibitors, does not involve nitrate reductase and AtNOA1 but requires IRT1, encoding a major plasma membrane transporter for iron but also Cd(2+). By analyzing the incidence of NO scavenging or inhibition of its synthesis during Cd(2+) treatment, we demonstrated that NO contributes to Cd(2+)-triggered inhibition of root growth. To understand the mechanisms underlying this process, a microarray analysis was performed in order to identify NO-modulated root genes up- and down-regulated during Cd(2+) treatment. Forty-three genes were identified encoding proteins related to iron homeostasis, proteolysis, nitrogen assimilation/metabolism, and root growth. These genes include IRT1. Investigation of the metal and ion contents in Cd(2+)-treated roots in which NO synthesis was impaired indicates that IRT1 up-regulation by NO was consistently correlated to NO's ability to promote Cd(2+) accumulation in roots. This analysis also highlights that NO is responsible for Cd(2+)-induced inhibition of root Ca(2+) accumulation. Taken together, our results suggest that NO contributes to Cd(2+) toxicity by favoring Cd(2+) versus Ca(2+) uptake and by initiating a cellular pathway resembling those activated upon iron deprivation.

  11. Ethylene and nitric oxide involvement in the up-regulation of key genes related to iron acquisition and homeostasis in Arabidopsis.

    Science.gov (United States)

    García, María J; Lucena, Carlos; Romera, Francisco J; Alcántara, Esteban; Pérez-Vicente, Rafael

    2010-09-01

    In a previous work it was shown that ethylene participates in the up-regulation of several Fe acquisition genes of Arabidopsis, such as AtFIT, AtFRO2, and AtIRT1. In this work the relationship between ethylene and Fe-related genes in Arabidopsis has been looked at in more depth. Genes induced by Fe deficiency regulated by ethylene were searched for. For this, studies were conducted, using microarray analysis and reverse transcription-PCR (RT-PCR), to determine which of the genes up-regulated by Fe deficiency are simultaneously suppressed by two different ethylene inhibitors (cobalt and silver thiosulphate), assessing their regulation by ethylene in additional experiments. In a complementary experiment, it was determined that the Fe-related genes up-regulated by ethylene were also responsive to nitric oxide (NO). Further studies were performed to analyse whether Fe deficiency up-regulates the expression of genes involved in ethylene biosynthesis [S-adenosylmethionine synthetase, 1-aminocyclopropane-1-carboxylate (ACC) synthase, and ACC oxidase genes] and signalling (AtETR1, AtCTR1, AtEIN2, AtEIN3, AtEIL1, and AtEIL3). The results obtained show that both ethylene and NO are involved in the up-regulation of many important Fe-regulated genes of Arabidopsis, such as AtFIT, AtbHLH38, AtbHLH39, AtFRO2, AtIRT1, AtNAS1, AtNAS2, AtFRD3, AtMYB72, and others. In addition, the results show that Fe deficiency up-regulates genes involved in both ethylene synthesis (AtSAM1, AtSAM2, AtACS4, AtACS6, AtACS9, AtACO1, and AtACO2) and signalling (AtETR1, AtCTR1, AtEIN2, AtEIN3, AtEIL1, and AtEIL3) in the roots.

  12. Localization of large conductance calcium-activated potassium channels and their effect on calcitonin gene-related peptide release in the rat trigemino-neuronal pathway.

    Science.gov (United States)

    Wulf-Johansson, H; Amrutkar, D V; Hay-Schmidt, A; Poulsen, A N; Klaerke, D A; Olesen, J; Jansen-Olesen, I

    2010-06-02

    Large conductance calcium-activated potassium (BK(Ca)) channels are membrane proteins contributing to electrical propagation through neurons. Calcitonin gene-related peptide (CGRP) is a neuropeptide found in the trigeminovascular system (TGVS). Both BK(Ca) channels and CGRP are involved in migraine pathophysiology. Here we study the expression and localization of BK(Ca) channels and CGRP in the rat trigeminal ganglion (TG) and the trigeminal nucleus caudalis (TNC) as these structures are involved in migraine pain. Also the effect of the BK(Ca) channel blocker iberiotoxin and the BK(Ca) channel opener NS11021 on CGRP release from isolated TG and TNC was investigated. By RT-PCR, BK(Ca) channel mRNA was detected in the TG and the TNC. A significant difference in BK(Ca) channel mRNA transcript levels were found using qPCR between the TNC as compared to the TG. The BK(Ca) channel protein was more expressed in the TNC as compared to the TG shown by western blotting. Immunohistochemistry identified BK(Ca) channels in the nerve cell bodies of the TG and the TNC. The beta2- and beta4-subunit proteins were found in the TG and the TNC. They were both more expressed in the TNC as compared to TG shown by western blotting. In isolated TNC, the BK(Ca) channel blocker iberiotoxin induced a concentration-dependent release of CGRP that was attenuated by the BK(Ca) channel opener NS11021. No effect on basal CGRP release was found by NS11021 in isolated TG or TNC or by iberiotoxin in TG. In conclusion, we found both BK(Ca) channel mRNA and protein expression in the TG and the TNC. The BK(Ca) channel protein and the modulatory beta2- and beta4-subunt proteins were more expressed in the TNC than in the TG. Iberiotoxin induced an increase in CGRP release from the TNC that was attenuated by NS11021. Thus, BK(Ca) channels might have a role in trigeminovascular pain transmission.

  13. Effect of calcitonin gene related peptide regulated nuclear factor kappa B signal transduction on c-kit+ cardiac stem cells in hypoxia state

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    Xian-ping LONG

    2015-11-01

    Full Text Available Objective To investigate the effects of calcitonin gene-related peptide (CGRP on the apoptosis of c-kit+ cardiac stem cells in hypoxia. Methods Ischemia and hypoxia models of c-kit+ cardiac stem cells were reproduced in vitro. The models were divided into hypoxia+CGRP group, hypoxia+CGRP8-37 (antagonist of CGRP group, hypoxia control group, normal oxygen group, and hypoxia+BAY11-7082 [antagonist of nuclear factor kappa B (NF-κB] group. NF-κB translocation after hypoxia was detected by immunofluorescence, and NF-κB channel proteins were determined with Western blotting. The NF-κB translocation and the expression of NF-κB channel proteins after CGRP intervention were detected, and the cell apoptosis rate after intervention was determined with flow cytometry in each group. Results Under hypoxia the NF-κB signal pathway was activated, and nuclear translocation occurred in NF-κBP65 (red fluorescence. Compared with hypoxia control group, the expressions of NF-κB related proteins such as P-I-κB, NF-κBP65 and NF-κBP50 decreased obviously (P<0.05. Compared with the hypoxia+CGRP group, the expressions of NF-κB related proteins increased significantly (P<0.05 as mentioned above in hypoxia+CGRP8-37 group. Both the early and late apoptotic rates declined in hypoxia+CGRP group compared with that of hypoxia control group (P<0.05, however, the early apoptotic rate increased markedly in hypoxia+CGRP8-37 group as compared with that of hypoxia+CGRP group (P<0.05. Conclusion Under hypoxia, CGRP may regulate the NF-κB signal pathway, and at the same time suppress the apoptosis of c-kit+ cardiac stem cells. DOI: 10.11855/j.issn.0577-7402.2015.10.03

  14. Wistar Rats Resistant to the Hypertensive Effects of Ouabain Exhibit Enhanced Cardiac Vagal Activity and Elevated Plasma Levels of Calcitonin Gene-Related Peptide

    Science.gov (United States)

    Ghadhanfar, Elham; Al-Bader, Maie; Turcani, Marian

    2014-01-01

    Ouabain is a cardiac glycoside produced in the adrenal glands and hypothalamus. It affects the function of all cells by binding to Na+/K+-ATPase. Several lines of evidence suggest that endogenous ouabain could be involved in the pathogenesis of essential (particularly, salt-sensitive) hypertension. However, information regarding the postulated hypertensive effect of the long-term administration of low-dose exogenous ouabain is inconsistent. This study was designed to help settle this controversy through the use of telemetric monitoring of arterial blood pressure and to elucidate the ouabain-induced alterations that could either promote or prevent hypertension. Ouabain (63 and 324 µg/kg/day) was administered subcutaneously to male Wistar rats. Radiotelemetry was used to monitor blood pressure, heart rate and measures of cardiovascular variability and baroreflex sensitivity. The continuous administration of ouabain for 3 months did not elevate arterial blood pressure. The low-frequency power of systolic pressure variability, urinary excretion of catecholamines, and cardiovascular response to restraint stress and a high-salt diet as well as the responsiveness to α1-adrenergic stimulation were all unaltered by ouabain administration, suggesting that the activity of the sympathetic nervous system was not increased. However, surrogate indices of cardiac vagal nerve activity based on heart rate variability were elevated. Molecular remodeling in mesenteric arteries that could support the development of hypertension (increased expression of the genes for the Na+/Ca2+ exchanger and Na+/K+-ATPase α2 isoform) was not evident. Instead, the plasma level of vasodilatory calcitonin gene-related peptide (CGRP) significantly rose from 55 (11, SD) in the control group to 89 (20, SD) pg/ml in the ouabain-treated rats (PTukey's = 18.10−5). These data show that long-term administration of exogenous ouabain does not necessarily cause hypertension in rodents. The augmented

  15. Calcitonin gene-related peptide (CGRP and its receptor components in human and rat spinal trigeminal nucleus and spinal cord at C1-level

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    Eftekhari Sajedeh

    2011-11-01

    Full Text Available Abstract Background Calcitonin gene-related peptide (CGRP has a key role in migraine pathophysiology and is associated with activation of the trigeminovascular system. The trigeminal ganglion, storing CGRP and its receptor components, projects peripheral to the intracranial vasculature and central to regions in the brainstem with Aδ- and C-fibers; this constitutes an essential part of the pain pathways activated in migraine attacks. Therefore it is of importance to identify the regions within the brainstem that processes nociceptive information from the trigeminovascular system, such as the spinal trigeminal nucleus (STN and the C1-level of the spinal cord. Immunohistochemistry was used to study the distribution and relation between CGRP and its receptor components - calcitonin receptor-like receptor (CLR and receptor activity modifying protein 1 (RAMP1 - in human and rat STN and at the C1-level, using a set of newly well characterized antibodies. In addition, double-stainings with CGRP and myelin basic protein (MBP, myelin, synaptophysin (synaptic vesicles or IB4 (C-fibers in general were performed. Results In the STN, the highest density of CGRP immunoreactive fibers were found in a network around fiber bundles in the superficial laminae. CLR and RAMP1 expression were predominately found in fibers in the spinal trigeminal tract region, with some fibers spanning into the superficial laminae. Co-localization between CGRP and its receptor components was not noted. In C1, CGRP was expressed in fibers of laminae I and II. The CGRP staining was similar in rat, except for CGRP positive neurons that were found close to the central canal. In C1, the receptor components were detected in laminae I and II, however these fibers were distinct from fibers expressing CGRP as verified by confocal microscopy. Conclusions This study demonstrates the detailed expression of CGRP and its receptor components within STN in the brainstem and in the spinal cord at C1

  16. Effect of calcitonin gene-related peptide and nerve growth factor on spatial learning and memory abilities of rats following focal cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Guangshun Zheng; Yongjie Yang; Xiubin Fang

    2006-01-01

    BACKGROUND: Calcitonin gene-related peptide (CGRP) and nerve growth actor (NGF) cam improve spatial learning and memory abilities of rats with cerebral ischemia/reperfusion; however, the effect of combination of them on relieving learning and memory injury following cerebral ischemia/reperfusion should be further studied.OBJECTIVE:To study the effects of exogenous CGRP and NGF on learning and memory abilities of rats with focal cerebral ischemia/reperfusion.DESIGN: Randomized controlled animal study.SETTING:Department of Neurosurgery, the Second Hospital of Xiamen; Department of Neurosurgery, the Second Affiliated Hospital of China Medical University; Department of Neurobiology, Basic Medical College of China Medical University.MATERIALS:A total of 30 healthy male SD rats, aged 8 weeks, of clean grade, weighing 250-300 g, were provided by Experimental Animal Department of China Medical University. All rats were randomly divided into sham-operation group, ischemia/reperfusion group and treatment group with 10 in each group. The main reagents were detailed as the follows: 100 g/L chloral hydrate, 0.5 mL CGRP (2 mg/L, Sigma Company, USA),and NGF (1 × 106 U/L, 0.5 mL, Siweite Company, Dalian).METHODS: The experiment was carried out in the Department of Neurobiology, Basic Medical College of China Medical University from February to duly 20055. Rat models of middle cerebral artery occlusion were established by method of occlusion, 2 hours after that rats were anesthetized and the thread was slightly drawn out for 10 mm under direct staring to perform reperfusion. Rats in the ischemia/reperfusion group received intraperitoneal injection of 1 mL saline via the abdomen at two hours later, while rats in the treatment group at 2 hours later received intraperitoneal injection of 2 mg/L CGRP (0.5 mL) and 1 ×106 U/L NGF (0.5 mL) once a day for 10 successive days. First administration was accomplished within 15 minutes after ischemia/reperfusion. Rats in the sham

  17. Levels of vasoactive intestinal peptide,cholecystokinin and calcitonin gene-related peptide in plasma and jejunum of rats following traumatic brain injury and underlying significance in gastrointestinal dysfunction

    Institute of Scientific and Technical Information of China (English)

    Chun-Hua Hang; Ji-Xin Shi; Jie-Shou Li; Wei Wu; Wei-Qin Li; Hong-Xia Yin

    2004-01-01

    AIM: To study the alterations of brain-gut peptides following traumatic brain injury (TBI) and to explore the underlying significance of these peptides in the complicated gastrointestinal dysfunction.METHODS: Rat models of focal traumatic brain injury were established by impact insult method, and divided into 6 groups (6 rats each group) including control group with sham operation and TBI groups at postinjury 3, 12, 24, 72 h, and d 7. Blood and proximal jejunum samples were taken at time point of each group and gross observations of gastrointestinal pathology were recorded simultaneously. The levels of vasoactive intestinal peptide (VIP) in plasma, calcitonin gene-related peptide (CGRP) and cholecystokinin (CCK) in both plasma and jejunum were measured by enzyme immunoassay (EIA). Radioimmunoassay (RIA) was used to determine the levels of VTP in jejunum. RESULTS: Gastric distension, delayed gastric emptying and intestinal dilatation with a large amount of yellowish effusion and thin edematous wall were found in TBI rats through 12 h and 72 h, which peaked at postinjury 72 h. As compared with that of control group (247.8±29.5 ng/L), plasma VIP levels were significantly decreased at postinjury 3, 12 and 24 h (106.7±34.1 ng/L, 148.7±22.8 ng/L, 132.8±21.6 ng/L,respectively), but significantly increased at 72 h (405.0±29.8 ng/L) and markedly declined on d 7 (130.7±19.3 ng/L).However, Plasma levels CCK and CGRP were significantly increased through 3 h and 7 d following TBT (126-691% increases), with the peak at 72 h. Compared with control (VIP, 13.6±1.4 ng/g; CGRP, 70.6±17.7 ng/g); VIP and CGRP levels in jejunum were significantly increased at 3 h after TBI (VIP, 35.4±5.0 ng/g; CGRP, 103.8±22.1 ng/g), anddeclined gradually at 12 h and 24 h (VIP, 16.5±1.8 ng/g, 5.5±1.4 ng/g; CGRP, 34.9±9.7 ng/g, 18.5±7.7 ng/g), but were significantly increased again at 72 h (VIP, 48.7±9.5 ng/g; CGRP, 142.1±24.3 ng/g), then declined in various degrees on d 7 (VIP, 3.8±1

  18. Ghrelin-related peptides do not modulate vasodilator nitric oxide production or superoxide levels in mouse systemic arteries.

    Science.gov (United States)

    Ku, Jacqueline M; Sleeman, Mark W; Sobey, Christopher G; Andrews, Zane B; Miller, Alyson A

    2016-04-01

    The ghrelin gene is expressed in the stomach where it ultimately encodes up to three peptides, namely, acylated ghrelin, des-acylated ghrelin and obestatin, which all have neuroendocrine roles. Recently, the authors' reported that these peptides have important physiological roles in positively regulating vasodilator nitric oxide (NO) production in the cerebral circulation, and may normally suppress superoxide production by the pro-oxidant enzyme, Nox2-NADPH oxidase. To date, the majority of studies using exogenous peptides infer that they may have similar roles in the systemic circulation. Therefore, this study examined whether exogenous and endogenous ghrelin-related peptides modulate NO production and superoxide levels in mouse mesenteric arteries and/or thoracic aorta. Using wire myography, it was found that application of exogenous acylated ghrelin, des-acylated ghrelin or obestatin to mouse thoracic aorta or mesenteric arteries failed to elicit a vasorelaxation response, whereas all three peptides elicited vasorelaxation responses of rat thoracic aorta. Also, none of the peptides modulated mouse aortic superoxide levels as measured by L-012-enhanced chemiluminescence. Next, it was found that NO bioactivity and superoxide levels were unaffected in the thoracic aorta from ghrelin-deficient mice when compared with wild-type mice. Lastly, using novel GHSR-eGFP reporter mice in combination with double-labelled immunofluorescence, no evidence was found for the growth hormone secretagogue receptor (GHSR1a) in the throracic aorta, which is the only functional ghrelin receptor identified to date. Collectively these findings demonstrate that, in contrast to systemic vessels of other species (e.g. rat and human) and mouse cerebral vessels, ghrelin-related peptides do not modulate vasodilator NO production or superoxide levels in mouse systemic arteries.

  19. 降钙素基因相关肽对实验性心肌肥厚的影响%The Impact of Calcitonin Gene Related Peptide on Experiment Cardiac Hypertrophy

    Institute of Scientific and Technical Information of China (English)

    张欣; 刘玉龙; 张海峰; 李春跃; 王美玲

    2011-01-01

    使用降钙素基因相关肽(CGRP)干预压力超负荷心肌肥厚大鼠,探讨CGRP与心肌组织中一氧化氮、内皮素含量变化的关系以及CGRP对心肌肥厚的影响,期望进一步揭示心肌肥厚的可能机制.采用腹主动脉缩窄的方法复制压力超负荷心肌肥厚大鼠模型.选取雄性Wistar大鼠40只,随机分为4组:对照组,缩窄组,CGRP组,卡托普利组(每组N=10).术后一周开始CGRP组给予CGRP8 μg/(kg·d-1),卡托普利组给予卡托普利30 mg/( kg·d-1).给药4周后处死动物,检测各项指标,光镜下观察心室肌组织结构变化,分别用放射免疫方法和硝酸还原法测定心室肌ET、NO的水平.与对照组相比的结果是缩窄组大鼠SBP、LVW/BW及心肌中ET水平明显升高(P<0.05),NO明显降低(P<0.05);干预组与缩窄组相比,SBP、LVW/BW及心肌中ET水平明显降低(P<0.05),心肌中NO水平升高(P<0.05),ET水平与左心系数呈正相关.光镜下观察结果:缩窄组与对照组比较,可见心肌纤维横径明显增粗,细胞核肥大,深染,异型,心肌纤维间隙增宽,间质纤维结缔组织增生明显.CGRP组和卡托普利组心肌纤维横径及细胞核较缩窄组缩小,间质增生程度较缩窄组明显减轻形态已经与对照组相近.说明:(1)心肌中NO水平下降、ET水平上调可能参与了压力超负荷性心肌肥厚的发生发展.(2) CGRP具有一定的逆转高血压心肌肥厚的作用,此作用与临床常用抗高血压药物卡托普利相近.%To investigate the relationship between calcitonin gene -related peptide (CGRP) and nitric oxide and endothelin ( ET) in myocardial tissue, and the impact of CGRP on cardiac hypertrophy of rats. Then the possible mechanism of cardiac hypertrophy is revealed. Hypertrophic myocardium was reproduced in rats by constricting abdominal aorta. 40 male Wistar rats were randomly divided into four groups; control group(N = 10) , coarctation group(Iv = 10) , CGRP group(N = 10

  20. Role of KATP channels in cephalic vasodilatation induced by calcitonin gene-related peptide, nitric oxide, and transcranial electrical stimulation in the rat

    DEFF Research Database (Denmark)

    Gozalov, Aydin; Jansen-Olesen, Inger; Klærke, Dan Arne;

    2008-01-01

    in migraine pathogenesis. We hypothesized that vasodilatation induced by CGRP and the NO donor glyceryltrinitrate (GTN) is mediated via K(ATP) channels. METHODS: We examined the effects of the K(ATP) channel inhibitor glibenclamide on dural and pial vasodilatation induced by CGRP, NO, and endogenously....... In anesthetized rats glibenclamide significantly attenuated CGRP induced dural and TES induced dural/pial artery dilatation (P = .001; P = .001; P = .005), but had no effect on dural/pial vasodilatation induced by GTN. In vitro glibenclamide failed to significantly inhibit CGRP- and GTN-induced vasodilatation....... CONCLUSIONS: These results show that a K(ATP) channel blocker in vivo but not in vitro inhibits CGRP, but not GTN-induced dilatation of dural and pial arteries, a mechanism thought to be important in migraine....

  1. Nitric oxide and vasoactive intestinal peptide as co-transmitters of airway smooth-muscle relaxation: analysis in neuronal nitric oxide synthase knockout mice.

    Science.gov (United States)

    Hasaneen, Nadia A; Foda, Hussein D; Said, Sami I

    2003-09-01

    Both vasoactive intestinal peptide (VIP) and nitric oxide (NO) relax airway smooth muscle and are potential co-transmitters of neurogenic airway relaxation. The availability of neuronal NO synthase (nNOS) knockout mice (nNOS-/-) provides a unique opportunity for evaluating NO. To evaluate the relative importance of NO, especially that generated by nNOS, and VIP as transmitters of the inhibitory nonadrenergic, noncholinergic (NANC) system. In this study, we compared the neurogenic (tetrodotoxin-sensitive) NANC relaxation of tracheal segments from nNOS-/- mice and control wild-type mice (nNOS(+/+)), induced by electrical field stimulation (EFS). We also examined the tracheal contractile response to methacholine and its relaxant response to VIP. EFS (at 60 V for 2 ms, at 10, 15, or 20 Hz) dose-dependently reduced tracheal tension, and the relaxations were consistently smaller (approximately 40%) in trachea from nNOS-/- mice than from control wild-type mice (p 0.05). Our data suggest that, in mouse trachea, NO is probably responsible for mediating a large (approximately 60%) component of neurogenic NANC relaxation, and a similar (approximately 50%) component of the relaxant effect of VIP. The results imply that NO contributes significantly to neurogenic relaxation of mouse airway smooth muscle, whether due to neurogenic stimulation or to the neuropeptide VIP.

  2. Peptide-Functionalized Fluorescent Particles for In Situ Detection of Nitric Oxide via Peroxynitrite-Mediated Nitration.

    Science.gov (United States)

    Chang, Jason Y H; Chow, Lesley W; Dismuke, W Michael; Ethier, C Ross; Stevens, Molly M; Stamer, W Daniel; Overby, Darryl R

    2017-08-01

    Nitric oxide (NO) is a free radical signaling molecule that plays a crucial role in modulating physiological homeostasis across multiple biological systems. NO dysregulation is linked to the pathogenesis of multiple diseases; therefore, its quantification is important for understanding pathophysiological processes. The detection of NO is challenging, typically limited by its reactive nature and short half-life. Additionally, the presence of interfering analytes and accessibility to biological fluids in the native tissues make the measurement technically challenging and often unreliable. Here, a bio-inspired peptide-based NO sensor is developed, which detects NO-derived oxidants, predominately peroxynitrite-mediated nitration of tyrosine residues. It is demonstrated that these peptide-based NO sensors can detect peroxynitrite-mediated nitration in response to physiological shear stress by endothelial cells in vitro. Using the peptide-conjugated fluorescent particle immunoassay, peroxynitrite-mediated nitration activity with a detection limit of ≈100 × 10(-9) m is detected. This study envisions that the NO detection platform can be applied to a multitude of applications including monitoring of NO activity in healthy and diseased tissues, localized detection of NO production of specific cells, and cell-based/therapeutic screening of peroxynitrite levels to monitor pronitroxidative stress in biological samples. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Erythropoietin and a nonerythropoietic peptide analog promote aortic endothelial cell repair under hypoxic conditions: role of nitric oxide

    Directory of Open Access Journals (Sweden)

    Heikal L

    2016-08-01

    Full Text Available Lamia Heikal,1 Pietro Ghezzi,1 Manuela Mengozzi,1 Blanka Stelmaszczuk,2 Martin Feelisch,2 Gordon AA Ferns1 1Brighton and Sussex Medical School, Falmer, Brighton, 2Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital and Institute for Life Sciences, Southampton, UK Abstract: The cytoprotective effects of erythropoietin (EPO and an EPO-related nonerythropoietic analog, pyroglutamate helix B surface peptide (pHBSP, were investigated in an in vitro model of bovine aortic endothelial cell injury under normoxic (21% O2 and hypoxic (1% O2 conditions. The potential molecular mechanisms of these effects were also explored. Using a model of endothelial injury (the scratch assay, we found that, under hypoxic conditions, EPO and pHBSP enhanced scratch closure by promoting cell migration and proliferation, but did not show any effect under normoxic conditions. Furthermore, EPO protected bovine aortic endothelial cells from staurosporine-induced apoptosis under hypoxic conditions. The priming effect of hypoxia was associated with stabilization of hypoxia inducible factor-1α, EPO receptor upregulation, and decreased Ser-1177 phosphorylation of endothelial nitric oxide synthase (NOS; the effect of hypoxia on the latter was rescued by EPO. Hypoxia was associated with a reduction in nitric oxide (NO production as assessed by its oxidation products, nitrite and nitrate, consistent with the oxygen requirement for endogenous production of NO by endothelial NOS. However, while EPO did not affect NO formation in normoxia, it markedly increased NO production, in a manner sensitive to NOS inhibition, under hypoxic conditions. These data are consistent with the notion that the tissue-protective actions of EPO-related cytokines in pathophysiological settings associated with poor oxygenation are mediated by NO. These findings may be particularly relevant to atherogenesis and postangioplasty restenosis. Keywords

  4. Effects of the prototype serotonin 5-HT(1B/1D) receptor agonist sumatriptan and the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP(8-37) on myocardial reactive hyperemic response in conscious dogs.

    Science.gov (United States)

    Lynch, Joseph J; Shen, You-Tang; Pittman, Tamara J; Anderson, Kenneth D; Koblan, Kenneth S; Gould, Robert J; Regan, Christopher P; Kane, Stefanie A

    2009-11-25

    The triptans, serotonin 5-HT(1B/1D) receptor agonists exemplified by sumatriptan, are a mainstay migraine therapy but have class labeling contraindicating their use in patients with coronary artery disease. Triptans constrict human coronary artery in vitro, and there are case reports of myocardial infarction in patients using sumatriptan. However, preclinical studies with sumatriptan in normal dogs have failed to demonstrate effects on resting coronary flow. Calcitonin gene-related peptide (CGRP) receptor antagonism, exemplified by the prototype CGRP receptor antagonist peptide CGRP(8-37), is a new antimigraine mechanism which also has been reported to have no effect on coronary flow in normal, non-stressed animals. The goal of the present studies was to compare the effects of sumatriptan (10microg/kg/min i.v.) and CGRP(8-37) (30microg/kg/min i.v.) on systemic and coronary hemodynamics in conscious dogs under resting conditions and during myocardial reactive hyperemia following a brief 15s of coronary artery occlusion. Neither CGRP(8-37) nor sumatriptan affected resting coronary flow. However, whereas CGRP(8-37) had no effect on myocardial reactive hyperemic response, sumatriptan reduced peak reactive hyperemic coronary artery blood flow (baseline vs treatment: 75.4+/-12.7 vs 60.0+/-10.3ml/min, Ptriptan effects on coronary vascular function.

  5. Vasoactive intestinal peptide and nitric oxide promote survival of adult rat myenteric neurons in culture

    DEFF Research Database (Denmark)

    Sandgren, Katarina; Lin, Zhong; Svenningsen, Åsa Fex;

    2003-01-01

    of VIP, NO donor, VIP antiserum, or NOS inhibitor. A marked loss of neurons was noted during culturing. VIP and NO significantly promoted neuronal survival. Corroborating this was the finding of an enhanced neuronal cell loss when cultures were grown in the presence of VIP antiserum or NOS inhibitor....... adaptation. The aim of this study was to evaluate whether VIP and nitric oxide (NO) influence survival of cultured, dissociated myenteric neurons. Neuronal survival was evaluated after 0, 4, and 8 days in culture. Influence of VIP and NO on neuronal survival was examined after culturing in the presence...

  6. Roles of calcitonin gene-related peptide family in pain and opioid tolerance%降钙素基因相关肽家族在疼痛和阿片耐受中的作用

    Institute of Scientific and Technical Information of China (English)

    刘芳薇; 洪炎国

    2013-01-01

    The calcitonin gene-related peptide (CGRP) family mainly includes CGRPt,CGRPβ,adrenomedullin,calcitonin and amylin.The members of CGRP family and their receptors are widely distributed in the central and peripheral nervous systems.Studies show that members of CGRP family such as CGRP and adrenomedullin play important roles in the transmission of nociceptive information.At spinal level,CGRP promotes the transmission of nociceptive information,spinal morphine tolerance,migraine,inflammatory pain and neuropathic pain.At superspinal level,CGRP suppresses the transmission of nociceptive information.Adrenomedullin is a pain-related neuropeptide which has recently been demonstrated.It facilitates the transmission of nociceptive information and is involved in the development and maintenance of opioid tolerance.The involvement of amylin and calcitonin in pain is not clear yet.%降钙素基因相关肽(calcitonin gene-related peptide,CGRP)家族成员主要包括CGRPα、CGRPβ、肾上腺髓质素(adrenomedullin,AM)、降钙素(calcitonin,CT)和胰淀粉样蛋白(amylin,AMY).CGRP家族成员及其受体广泛分布于哺乳动物中枢和外周神经系统.研究表明,CGRP、AM等CGRP家族成员在伤害性信息传递过程中具有重要作用.在脊髓水平,CGRP促进痛觉信息传递、脊髓阿片耐受、偏头痛、炎性痛和神经病理性痛;在脊髓以上水平,CGRP则抑制痛觉信息的传递.AM是近年来才证实的与疼痛感受有密切关系的神经多肽,在脊髓水平促进痛觉信息的传递,在阿片耐受形成和维持中亦有重要作用.AMY和CT与疼痛的关系尚不十分明确.

  7. Novel Peptide for Attenuation of Hypoxia-Induced Pulmonary Hypertension via Modulation of Nitric Oxide Release and Phosphodiesterase -5 Activity

    Science.gov (United States)

    Hu, Hanbo; Zharikov, Sergey; Patel, Jawaharlal M.

    2012-01-01

    Pulmonary vascular endothelial nitric oxide (NO) synthase (eNOS)-derived NO is the major stimulant of cyclic guanosine 5’ monophosphate (cGMP) production and NO/cGMP-dependent vasorelaxation in the pulmonary circulation. We recently synthesized multiple peptides and reported that an eleven amino acid (SSWRRKRKESS) peptide (P1) but not scrambled P1 stimulated the catalytic activity but not expression of eNOS and causes NO/cGMP-dependent sustained vasorelaxation in isolated pulmonary artery (PA) segments and in lung perfusion models. Since cGMP levels can also be elevated by inhibition of phosphodiesterase type 5 (PDE-5), this study was designed to test the hypothesis that P1-mediated vesorelaxation is due to its unique dual action as NO-releasing PDE-5 inhibitor in the pulmonary circulation. Treatment of porcine PA endothelial cells (PAEC) with P1 caused time-dependent increase in intracellular NO release and inhibition of the catalytic activity of cGMP-specific PDE-5 but not PDE-5 protein expression leading to increased levels of cGMP. Acute hypoxia-induced PA vasoconstriction ex-vivo and continuous telemetry monitoring of hypoxia (10% oxygen)-induced elevated PA pressure in freely moving rats were significantly restored by administration of P1. Chronic hypoxia (10% oxygen for 4 weeks)-induced alterations in PA perfusion pressure, right ventricular hypertrophy, and vascular remodeling were attenuated by P1 treatment. These results demonstrate the potential therapeutic effects of P1 to prevent and/or arrest the progression of hypoxia-induced PAH via NO/cGMP-dependent modulation of hemodynamic and vascular remodeling in the pulmonary circulation. PMID:22465621

  8. Effects of alpha-calcitonin gene-related peptide on osteoprotegerin and receptor activator of nuclear factor-κB ligand expression in MG-63 osteoblast-like cells exposed to polyethylene particles

    Directory of Open Access Journals (Sweden)

    Kauther Max D

    2010-11-01

    Full Text Available Abstract Background Recent studies demonstrated an impact of the nervous system on particle-induced osteolysis, the major cause of aseptic loosening of joint replacements. Methods In this study of MG-63 osteoblast-like cells we analyzed the influence of ultra-high molecular weight polyethylene (UHMWPE particles and the neurotransmitter alpha-calcitonin gene-related peptide (CGRP on the osteoprotegerin/receptor activator of nuclear factor-κB ligand/receptor activator of nuclear factorκB (OPG/RANKL/RANK system. MG-63 cells were stimulated by different UHMWPE particle concentrations (1:100, 1:500 and different doses of alpha-CGRP (10-7 M, 10-9 M, 10-11 M. RANKL and OPG mRNA expression and protein levels were measured by RT-PCR and Western blot. Results Increasing particle concentrations caused an up-regulation of RANKL after 72 hours. Alpha-CGRP showed a dose-independent depressive effect on particle-induced expression of RANKL mRNA in both cell-particle ratios. RANKL gene transcripts were significantly (P -7 M lead to an up-regulation of OPG protein. Conclusion In conclusion, a possible osteoprotective influence of the neurotransmitter alpha-CGRP on particle stimulated osteoblast-like cells could be shown. Alpha-CGRP might be important for bone metabolism under conditions of particle-induced osteolysis.

  9. Appetite suppressive effects of yeast hydrolysate on nitric oxide synthase (NOS) expression and vasoactive intestinal peptide (VIP) immunoreactivity in hypothalamus.

    Science.gov (United States)

    Jung, E Y; Suh, H J; Kim, S Y; Hong, Y S; Kim, M J; Chang, U J

    2008-11-01

    To investigate the effects of yeast hydrolysate on appetite regulation mechanisms in the central nervous system, nitric oxide synthase (NOS) expression and vasoactive intestinal peptide (VIP) immunoreactivity in the paraventricular nucleus (PVN) and ventromedial hypothalamic nucleus (VMH) of the hypothalamus were examined. Male Sprague-Dawley (SD) rats were assigned to five groups: control (normal diet), BY-1 and BY-2 (normal diet with oral administration of 0.1 g and 1.0 g of yeast hydrolysate yeast hydrolysate 10-30 kDa/kg body weight, respectively). The body weight gain in the BY groups was less than that in the control. In particular, the weight gain of the BY-2 group (133.0 +/- 5.1 g) was significantly lower (p yeast hydrolysate of <10 kDa reduced the body weight gain and body fat in normal diet-fed rats and increased the lipid energy metabolism by altering the expression of NOS and VIP in neurons.

  10. Role of vasoactive intestinal peptide and nitric oxide in the modulation of electroacupucture on gastric motility in stressed rats

    Institute of Scientific and Technical Information of China (English)

    Guo-Ming Shen; Mei-Qi Zhou; Guan-Sun Xu; Ying Xu; Gang Yin

    2006-01-01

    AIM: To investigate the effects and mechanisms of vasoactive intestinal peptide (VIP) and nitric oxide (NO)in the modulation of electroacupucture (EA) on gastric motility in restrained-cold stressed rats.METHODS: An animal model of gastric motility disorder was established by restrained-cold stress. Gastric myoelectric activities were recorded by electrogastroent erography (EGG). VIP and NO concentrations in plasma and gastric mucosal and bulb tissues were detected by radioimmunoassay (RIA). VIP expression in the gastric wails was assayed using avidin-biotin-peroxidase complex (ABC) and image analysis.RESULTS: In cold restrained stressed rats, EGG was disordered and irregular. The frequency and amplitude of gastric motility were higher than that in control group (P< 0.01). VIP and NO contents of plasma, gastric mucosal and bulb tissues were obviously decreased (P < 0.01).Following EA at "Zusanli" (ST36), the frequency and amplitude of gastric motility were obviously lowered (P <0.01), while the levels of VIP and NO in plasma, gastric mucosal and bulb tissues increased strikingly (P < 0.01,P < 0.05) and expression of VIP in antral smooth muscle was elevated significantly (P < 0.01) in comparison with those of model group.CONCLUSION: VIP and NO participate in the modulatory effect of EA on gastric motility. EA at "Zusanli"acupoint (ST36) can improve gastric motility of the stressed rats by increasing the levels of VIP and NO.

  11. Glucagon-like peptide-1 activates endothelial nitric oxide synthase in human umbilical vein endothelial cells

    Institute of Scientific and Technical Information of China (English)

    Li DING; Jin ZHANG

    2012-01-01

    To investigate the effects of glucagon-like peptide-1 (GLP-1) on endothelial NO synthase (eNOS) in human umbilical vein endothelial cells (HUVECs),and elucidate whether GLP-1 receptor (GLP-1R) and GLP-1(9-36) are involved in these effects.Methods:HUVECs were used.The activity of eNOS was measured with NOS assay kit.Phosphorylated and total eNOS proteins were detected using Western blot analysis.The level of eNOS mRNA was quantified with real-time RT-PCR.Results:Incubation of HUVECs with GLP-1 (50-5000 pmol/L) for 30 min significantly increased the activity of eNOS.Incubation of HUVECs with GLP-1 (500-5000 pmol/L) for 5 or 10 min increased eNOS phosphorylated at ser-1177.Incubation with GLP-1 (5000 pmol/L) for 48 h elevated the level of eNOS protein,did not affect the level of eNOS mRNA.GLP-1R agonists exenatide and GLP-1(9-36) at the concentration of 5000 pmol/L increased the activity,phosphorylation and protein level of eNOS.GLP-1R antagonist exendin(9-39) or DPP-4 inhibitor sitagliptin,which abolished GLP-1(9-36) formation,at the concentration of 5000 pmol/L partially blocked the effects of GLP-1 on eNOS.Conclusion:GLP-1 upregulated the activity and protein expression of eNOS in HUVECs through the GLP-1R-dependent and GLP-1(9-36)-related pathways.GLP-1 may prevent or delay the formation of atherosclerosis in diabetes mellitus by improving the function of eNOS.

  12. The mesurements of calcitonin gene-related peptide and substance P in patients with chronic cor pulmonale%慢性肺源性心脏病患者血浆CGRP和SP水平的测定

    Institute of Scientific and Technical Information of China (English)

    王珍珍; 谢新立; 阮翘

    2010-01-01

    目的 探讨血浆降钙素基因相关肽(calcitonin gene-related peptide,CGRP)和P物质(substance P, SP)在慢性肺源性心脏病(肺心病)发生发展中的病理生理作用.方法 采用放射免疫分析法测定30例肺心病组急性发作期和治疗后缓解期及20例正常对照组血浆CGRP和SP 浓度.肺心病组同时检测动脉氧分压(PaO2).结果 血浆CGRP水平肺心病组急性发作期(12±5)pg/ml和治疗后缓解期(19±7)pg/ml均低于正常对照组(24±5)pg/ml,差异有统计学意义(P0.05).PaO2急性发作期和治疗后缓解期分别为(6.3±2.0)kPa、(9.5±1.6)kPa,差异有统计学意义(P<0.01).结论 慢性缺氧与血浆CGRP、SP水平下降有关,尤其是CGRP,缺氧时两者的变化共同促进了肺动脉高压的形成,在慢性肺源性心脏病发生发展中起重要作用.%Objective To evaluate the pathophysiological role of calcitonin gene-related peptide(CGRP) and substance P(SP) in patients with chronic cor pulmonale. Methods The levels of plasma CGRP and SP were determined by radioimmunoassay in 30 patients with chronic cor pulmonale before and after treatment, and their mean pulmonary aterial pressure(PaO2) were detected. Control group consisted of 20 healthy subjects and the levels of plasma CGRP and cor pulmonale group, plasma CGRP levels before treatment(12±5 pg/ml)were lower than those after treatment(19±7)pg/ml(P<0.01). Both of them were lower than those in control group(24±5)pg/ml(P<0.01). Plasma SP levels before treatment(39±12)pg/ml were significantly lower than those after treatment(46±11)pg/ml (P<0.01), and control group(45±8)pg/ml(P<0.05), and there after treatment in chronic cor pulmonale group, PaO2 were (6.3±2.0)kPa and (9.5±1.6)kPa respectively, the former was significantly lower than the latter(P<0.01). Conclusions This study suggests that hypoxia has a statistical relationship with the decrease of plasma CGRP and SP levels in patients with chronic cor pulmonale, particularly with

  13. Metal-activated C-peptide Facilitates Glucose Clearance and the Release of a Nitric Oxide Stimulus via the GLUT1 Transporter

    Science.gov (United States)

    Meyer, Jennifer A.; Froelich, Jennifer M.; Reid, Gavin E.; Karunarathne, Welivitya K.A.; Spence, Dana M.

    2008-01-01

    Objective: Proinsulin C-peptide has been implicated in reducing complications associated with diabetes and improving blood flow. We hypothesized that incubation of erythrocytes with C-peptide would improve the ability of these cells to release ATP, a stimulus of nitric oxide production. Research Design and Methods: Erythrocytes obtained from rabbits (n=11) and humans (healthy and those with type 2 diabetes, n=7) were incubated with C-peptide (in the absence and presence of Fe (II) and Cr (III)) and the resulting ATP release was measured via chemiluminescence. This release was also measured in the presence and absence of phloretin, an inhibitor of the glucose transporter GLUT1, and mannose, a glycolysis inhibitor. To determine glucose transport, 14C-labelled glucose was added to erythrocytes in the presence and absence of the C- peptide/metal complex and the aforementioned inhibitors. Results: The release of ATP from the erythrocytes of patients with diabetes increased from 64 nmol/l (± 13 nmol/l) to 260 nmol/l (± 39 nmol/l) upon incubation of the cells in C-peptide. The C-peptide activity was dependent upon binding to Fe (II), which was extended upon binding to Cr (III). The increase in ATP release from the erythrocytes is due to metal-activated C-peptide stimulation of glucose transfer into the erythrocytes via the GLUT1 transporter. In the presence of C-peptide complexed to Cr (III), the amount of glucose transferred into the erythrocyte increased by 31%. Conclusions: When complexed to Fe (II) or Cr (III), C-peptide has the ability to promote ATP release from erythrocytes. This release is due to an increase in glucose transport through the GLUT1 transporter. PMID:17965850

  14. Hypergravity differentially modulates cGMP efflux in human melanocytic cells stimulated by nitric oxide and natriuretic peptides

    Science.gov (United States)

    Ivanova, K.; Stieber, C.; Lambers, B.; Block, I.; Krieg, R.; Wellmann, A.; Gerzer, R.

    Nitric oxide NO plays a key role in many patho physiologic processes including inflammation and skin cancer The diverse cellular effects of NO are mainly mediated by activation of the soluble guanylyl cyclase sGC isoform that leads to increases in intracellular cGMP levels whereas the membrane-bound isoforms serve as receptors for natriuretic peptides e g ANP In human skin epidermal melanocytes represent the principal cells for skin pigmentation by synthesizing the pigment melanin Melanin acts as a scavenger for free radicals that may arise during metabolic stress as a result of potentially harmful effects of the environment In previous studies we found that long-term exposure to hypergravity stimulated cGMP efflux in normal human melanocytes NHMs and non-metastatic melanoma cells at least partly by an enhanced expression of the multidrug resistance proteins MRP and cGMP transporters MRP4 5 The present study investigated whether hypergravity generated by centrifugal acceleration may modulate the cGMP efflux in NO-stimulated NHMs and melanoma cells MCs with different metastatic potential The NONOates PAPA-NO and DETA-NO were used as direct NO donors for cell stimulation In the presence of 0 1 mM DETA-NO t 1 2 sim 20 h long-term application of hypergravity up to 5 g for 24 h reduced intracellular cGMP levels by stimulating cGMP efflux in NHMs and non-metastatic MCs in comparison to 1 g whereas exposure to 5 g for 6 h in the presence of 0 1 mM PAPA-NO t 1 2 sim 30 min was not effective The hypergravity-stimulated

  15. Etiology of Alzheimer's disease: kinetic, thermodynamic and fluorimetric analyses of interactions of pseudo Aβ-peptides with neuronal nitric oxide synthase.

    Science.gov (United States)

    Padayachee, E R; Whiteley, C G

    2013-10-01

    Aggregated β-amyloid deposit is a hallmark in the neuropathology of Alzheimer's disease but their mechanism of formation still remains unresolved. Previously we reported that a normal pentapeptide Aβ(17-21) and glycine zipper peptide Aβ(29-33) strongly inhibited nitric oxide synthase and rapidly initiated fibrillogenesis. Critical amino acids within these fragments were not identified. We now report on the interaction of four pseudo-peptides with nNOS - two peptides with a reversed amino acid sequence [Aβ(17-21r); Aβ(29-33r)] and two peptides with Phe19, Phe20 and Ile31, Ile32 substituted with polar glutamic acid [Aβ(17-21p); Aβ(29-33p)]. It was shown that while the inhibitor constants (Ki) increased 2-3 fold for each of the pseudo-peptides when compared with the normal peptides the dissociation constant Kd increased between 20 and 50 fold. Stern-Volmer fluorescence quenching constants (K(SV)) for Aβ(17-21p) and Aβ(29-33p) were 7.2×10(-3) and 6.1×10(-3) μM(-1) respectively at 298 K some 2-3 fold lower than the corresponding Aβ(17-21r); Aβ(29-33r). With temperature increase there was an increase in K(SV) and Kd, suggesting a dynamic quenching mechanism. Thermodynamic parameters, ΔH, ΔS and ΔG were all positive indicating endothermic, non-spontaneous, hydrophobic-hydrophobic associations of the pseudo-peptides with the enzyme. By FRET analysis the efficiency of fluorescence transfer between enzyme tryptophans and the pseudo-peptides was 90% (compared to 97% for the natural substrate). The distance the tryptophans moved after interaction with Aβ(17-21r) and Aβ(17-21p) was 10% greater, while for Aβ(29-33r) and Aβ(29-33p) it was 20-25% greater, than with the normal peptides; the fluorescence intensity was 20-75% higher. This increase in distance, fluorescent intensity and transfer efficiency illustrate an increase in interaction energy for the pseudo-peptides with nNOS lending support for the strategic position of the Phe19, Phe20, Ile31 and Ile32

  16. Effect of electroacupuncture on thermal pain threshold and expression of calcitonin-gene related peptide, substance P and γ-aminobutyric acid in the cervical dorsal root ganglion of rats with incisional neck pain.

    Science.gov (United States)

    Qiao, Li-Na; Liu, Jun-Ling; Tan, Lian-Hong; Yang, Hai-Long; Zhai, Xu; Yang, Yong-Sheng

    2017-08-01

    Acupuncture therapy effectively reduces post-surgical pain, but its mechanism of action remains unclear. The aim of this study was to investigate whether expression of γ-aminobutyric acid (GABA) and the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) in the primary sensory neurons of cervical dorsal root ganglia (DRG) are involved in electroacupuncture (EA)-induced analgesia in a rat model of incisional neck pain. The pain model was established by making a longitudinal midline neck incision in 60 rats. Another 15 rats underwent sham surgery (normal group). Post-incision, 15 rats remained untreated (model group) and 45 rats underwent EA (frequency 2/100 Hz, intensity 1 mA) at bilateral LI18, LI4-PC6 or ST36-GB34 (n=15 each) for 30 min at 4 hours, 24 hours, and 48 hours post-surgery, followed by thermal pain threshold (PT) measurement. 30 min later, the rats were euthanased and cervical (C3-6) DRGs removed for measurement of immunoreactivity and mRNA expression of SP/CGRP and the GABAergic neuronal marker glutamic acid decarboxylase 67 (GAD67). Thermal PT was significantly lower in the model group versus the normal group and increased in the LI18 and LI4-PC6 groups but not the ST36-GB34 group compared with the model group. Additionally, EA at LI18 and LI4-PC6 markedly suppressed neck incision-induced upregulation of mRNA/protein expression of SP/CGRP, and upregulated mRNA/protein expression of GAD67 in the DRGs of C3-6 segments. EA at LI18/LI4-PC6 increases PT in rats with incisional neck pain, which is likely related to downregulation of pronociceptive mediators SP/CGRP and upregulation of the inhibitory transmitter GABA in the primary sensory neurons of cervical DRGs. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. Influence of Buyang Huanwu Decoction on Endothelin and Calcitonin Gene-related Peptide in Patients with Migraine%补阳还五汤对偏头痛患者血浆CGRP和ET的影响

    Institute of Scientific and Technical Information of China (English)

    张洪涛; 张淑玲

    2013-01-01

    目的:观察补阳还五汤对偏头痛患者血浆降钙素基因相关肽(CGRP)和内皮素(ET)的影响.方法:72例偏头痛患者随机分为两组,西药组36例,口服尼莫地平20~40 mg,每日3次;急性发作期加服麦角胺咖啡因片1~2片/次.中药组36例,给予补阳还五汤,每日1剂,水煎分早晚服.两组均连续治疗3个月.治疗前、后监测偏头痛发作频率、持续时间、严重程度、药物的不良反应、CGRP和ET的水平,并与36例正常人对照.结果:中药组的总有效率显著高于西药组(P<0.05);两组偏头痛患者均较正常人ET明显增高(均P<0.01),CGRP明显降低(均P<0.01);西药组和中药组均可降低ET水平、偏头痛积分,提高CGRP水平(均P<0.01),但中药组比西药组作用更明显(均P<0.01).服用补阳还五汤未发生明显的不良的反应.结论:补阳还五汤能通过调节血管活性物质CGRP,ET水平,改善血管的异常舒缩状况,从而达到缓解偏头痛的作用.%Objective: To observe the influence of Buyang Huanwu decoction on endothelin (ET) and calcitonin gene-related peptide (CGRP) in patients with migraine. Method: Seventy two patients with migraine were divided into 2 groups randomly, 36 patients in western medicine group were treated by Nimodipine tablets 20-40 mg once, 3 times a day, To add ergotamine caffeine 1-2 tablets once in acute seizure phase. 36 patients in Chinese medicine group were treated by Buyang Huanwu decoction, take a decoction a day, divided into morning and evening. Patients had received continuous treatment for three months. Migraine frequency, duration, severity, adverse drug reactions and the concentration of plasma CGRP and ET were monitored before and after treatment. And comparative study with 36 cases of normal. Result: The total efficiency of traditional Chinese medicine group was significantly higher than that of the western medicine group (P < 0. 05 ) ; ET in patients with migraine was significantly

  18. Cloning and expression analysis of calcitonin gene related peptide (CGRP) in Gekko japonicus%多疣壁虎降钙素基因相关肽基因的克隆及表达分析

    Institute of Scientific and Technical Information of China (English)

    任丽洁; 王锐利; 王莹洁; 王勇军

    2012-01-01

    Objective To clone the full length of calcitonin gene related peptide (CGRP) in Gekko japonicus, and investigate the expression changes of CGRP in the spinal cord regeneration after tail amputation. Methods Full length of CGRP cDNA was obtained from Gekko by rapid amplification of cDNA ends ( RACE). Then the expression and distribution of CGRP in the proximal spinal cord were compared at different time points after tail amputation (P <0.05) by in situ hybridization (ISH) and RT-PCR. Results CGRP cDNA spans 1 002 bp. RT-PCR results showed that CGRP mRNA was remarkably up-regulated in the spinal cord proximal to the amputation at Id after tail amputation(P <0.05). In situ hybridization showed that CGRP mRNA was expressed mainly in the gray matter of spinal cord and scarcely in white matter. After tail amputation, the expression of CGRP was significantly increased in the proximal spinal cord of injury, at 1 d (P < 0.05). Conclusion Full length of CGRP cDNA was obtained. CGRP was remarkably up-regulated in the spinal cord proximal to the amputation at Id after tail amputation. CGRP synthesized and released from neural system may participate in regulating immunoreaction or wound healing.%目的 克隆多疣壁虎降钙素基因相关肽(CGRP)基因的全长序列;研究CGRP在壁虎断尾损伤后脊髓再生过程中的表达变化.方法 应用cDNA末端快速扩增(RACE)技术获得壁虎CGRP的cDNA全长序列;制备壁虎断尾损伤模型,应用RT-PCR和原位杂交方法检测壁虎断尾后该基因在中枢神经系统的表达变化.结果 RACE方法获得CGRPcDNA全长序列1 002bp;RT-PCR检测结果表明,壁虎断尾损伤1d后断端近侧脊髓中mRNA表达呈明显上升趋势且转录水平最高(P<0.05);脊髓原位杂交结果显示,CGRP mRNA阳性信号主要分布于脊髓灰质中,白质中少量表达;断尾损伤后1d阳性信号明显增强(P<0.05).结论 该试验克隆得到了壁虎CGRP cDNA的全长

  19. Inhibition of calcitonin gene-related peptide and insulin-like growth factor: a potential new therapeutic strategy to reduce bone pain in bone metastases of breast cancer%抑制降钙基因相关肽和胰岛素样生长因子:一种减轻乳腺癌骨转移患者骨痛的新策略

    Institute of Scientific and Technical Information of China (English)

    梁燕

    2010-01-01

    @@ 2009年圣·安东尼奥会议上,Teruhisa Sakurai等作了题名为"Inhibition of calcitonin gene-related peptide and insulin-like growth factor:a potential new therapeutic strategy to reduce bone pain in bone metastases of breastcancer"的报告.

  20. 支气管哮喘患儿不同治疗方法内皮素和降钙素基因相关肽结果比较%Study of endothelin and calcitonin gene-related peptide levels in children with bronchial asthma by different therapies

    Institute of Scientific and Technical Information of China (English)

    吕汉文; 卢远达; 徐淑兰; 叶彩丽; 林灿华; 周翔

    2002-01-01

    Background: Bronchial asthma is an allergic pulmonary disease. The attack is mostly induced by the inhalation of or contact with allergens, such as pollens, dusts, insects (such as mite), germs, etc. During the attack, patients have severe dyspnea which is due to spasm of bronchial smooth muscles, swelling of the bronchial mucosa, and hypersecretion of the mucus, leading to bronchial obstruction. To observe the endothelin(ET) and calcitonin gene related peptide(CGRP) changes in treating children with bronchial asthma by dopamine( DP), dobutamine( DOB),and regitine.

  1. Effects of Simo decoction on calcitonin gene-related peptide and ghrelin in diabetic rats%四磨汤对糖尿病大鼠降钙素基因相关肽及饥饿素的影响

    Institute of Scientific and Technical Information of China (English)

    戴迟兵; 刘娜; 钱伟; 侯晓华

    2012-01-01

    Objective To investigate the effects of Simo decoction on ghrelin and calcitonin gene-related peptide (CGRP) in diabetic rats.Methods A total of 48 SD rats were divided into healthy control group,diabetes group (DM),DM treated with low dose Simo decoction group (DMTL),DM treated with medium dose Simo decoction group (DM-TM),DM treated with high dose Simo decoction group (DM-TH) and DM prevented with medium dose Simo decoction group (DMPM) ; there were eight rats in each group.The rats of DM group and other intervention groups were intraperitoneally injected with 1% streptozotoein (STZ) to establish the model.The rats of healthy control group were injected with solvent.At eight weeks after the model successfully established,the rats of each intervention group were gavaged with low dose of Simo decoction (0.15 ml · kg-1 · d-1 ),medium dose of Simo decoction (1.5 ml · kg-1 · d-1 ) and high dose of Simo decoction (3.0 ml · kg-1 ·d-1 ) for two weeks; the rats of control group and DM groups were gavaged with equal volume of 0.9%NaCl.The rats of DM-PM group were gavaged with Simo decoction at 1.5 ml · kg-1 · d-1 for 10 weeks after the model successfully established.Rats were sacrificed at the end of drug intervention and gastric antrum tissues were dissociated for detecting the expression of ghrelin and CGRP by real time polymerase chain reaction (PCR).The data were analyzed by one way ANOVA and t test.Results There was no significant difference in ghrelin expression at mRNA level in gastric antrum tissues between diabetic rats and control group.However after intervened by low dose and medium dose of Simo decoction,the ghrelin expression increased (1.45 ± 0.34,1.87 ± 0.68 compared with 0.87 ±0.28,Dunnett's T3 test,P<0.05).There was no effects of high dose Simo decoction on the expression of ghrelin in diabetic rats.There was no significant difference in ghrelin between DM-TM and DM-PM.The expression of CGRP at mRNA level in gastric antrum tissues of

  2. Stimulation of natriuretic peptide receptor C attenuates accumulation of reactive oxygen species and nitric oxide synthesis in ammonia-treated astrocytes.

    Science.gov (United States)

    Skowrońska, Marta; Zielińska, Magdalena; Albrecht, Jan

    2010-11-01

    Oxidative and nitrosative stress contribute to ammonia-induced astrocytic dysfunction in hepatic encephalopathy. Treatment of cultured astrocytes with 5 mmol/L ammonium chloride ('ammonia') increased the production of reactive oxygen species (ROS), including the toxic NADPH oxidase reaction product, •O(2)(-). Atrial natriuretic peptide (ANP), natriuretic peptide C and a selective natriuretic peptide receptor (NPR)-C ligand, cANP((4-23),) each decreased the total ROS content both in control cells and cells treated with ammonia. However, attenuation of •O(2)(-) accumulation by ANP and cANP((4-23),) was observed in ammonia-treated cells only and the effect of cANP((4-23)) was decreased when the NADPH oxidase-regulatory protein G(iα-2) was blocked with a specific anti-G(iα-2) antibody. Although in contrast to ANP, cANP((4-23)) did not elevate the cGMP content in control astrocytes, it decreased cAMP content and reduced the expression of G(iα-2), the NADPH oxidase-regulatory protein. The results show the presence of functional NPR-C in astrocytes, activation of which (i) attenuates basal ROS production, and (ii) prevents excessive accumulation of the toxic ROS species, •O(2)(-) by ammonia. Ammonia, ANP and cANP((4-23)) added separately, each stimulated formation of NO(x) (nitrates + nitrites) which was associated with up-regulation of the activity [cANP((4-23))] or/and expression (ammonia) of the endothelial isoform of nitric oxide synthase. However, the ammonia-induced increase of NO(x) was not augmented by co-addition of ANP, and was reduced to the control level by co-addition of cANP((4-23)) , indicating that activation of NPR-C may also reduce nitrosative stress. Future hepatic encephalopathy therapy might include the use of cANP((4-23)) or other NPR-C agonists to control oxidative/nitrosative stress induced by ammonia.

  3. 降钙素基因相关肽和BIBN4096BS对麻醉大鼠心肌缺血的作用%Effects of calcitonin gene-related peptide and BIBN4096BS on myocardial ischemia in anesthetized rats

    Institute of Scientific and Technical Information of China (English)

    Dong-Mei WU; Pieter A van ZWIETEN; Henri N DOODS

    2001-01-01

    AIM: The cardioprotective effect of calcitonin gene related peptide (CGRP) was investigated in an ischemia rat model. METHODS: Ischemia-reperfusion injury was provoked by 60 min left main coronary artery occlu sion followed by 60 min of reperfusion in anesthetized rats. The transverse slices of ventricles were stained by 2,3,5-triphenyltetrazolium chloride to determine the in farct area. Plasma creatine phosphokinase levels were determined by means of a creatine phosphokinase (CPK) kit. A radioimmunoassay was used to determine plasma CGRP levels. RESULTS: Intravenous infusion of CGRP (1 nmol· kg- 1·h-1) 10 min before occlusion until the end of reperfusion reduced infarct size by 89 % ± 5 %. The reduction in infarct size was accompanied by a decrease in circulating levels of creatine phosphokinase. Infusion of the same dose of CGRP commehcing from the start of reperfusion until its end induced a 40 % ± 3 % reduction of the infarct size. The cardioprotective effects of CGRP were blocked by the novel CGRP antagonist BIBN4096BS (20 nmol· kg-1 · h-1 ). Although cardiac ischemia resulted in an almost 50 % increase in plasma CGRP levels in blood sampled from right cardiac ventri cle, intravenous infusion of the CGRP antagonist BIBN4096BS before occlusion until the end of reperfusion had no statistically significant effect on the infarct size. CONCLUSION: The present study demonstrates that CGRP is a potent myocardial protective substance.

  4. Increased circulating calcitonin gene-related peptide (CGRP) in cirrhosis

    DEFF Research Database (Denmark)

    Bendtsen, Flemming; Schifter, S; Henriksen, Jens Henrik

    1991-01-01

    with minor disorders (59 vs. 46 pmol/l, p less than 0.01), as well as with 232 healthy persons (37 pmol/l, p less than 0.0001). Moreover, circulating CGRP increased significantly with the severity of cirrhosis (Child-Turcotte group A, 56; group B, 59; group C, 71 pmol/l; p less than 0.025). No significant...

  5. Calcitonin Gene-Related Peptide and Migraine: Implications for Therapy

    NARCIS (Netherlands)

    U. Arulmani (Udayasankar)

    2004-01-01

    textabstractIt is clearly evident from the literature that headache has troubled mankind from the dawn of civilization (Rapoport & Edmeads, 2000). A variety of methods have been used throughout the ages in an attempt to alleviate or cure this pain; these may have been the most appropriate at that

  6. Increased expression and local accumulation of the Prion Protein, Alzheimer Aβ peptides, superoxide dismutase 1, and Nitric oxide synthases 1 & 2 in muscle in a rabbit model of diabetes

    Directory of Open Access Journals (Sweden)

    Bitel Claudine L

    2010-09-01

    Full Text Available Abstract Background Muscle disease associated with different etiologies has been shown to produce localized accumulations of amyloid and oxidative stress-related proteins that are more commonly associated with neurodegeneration in the brain. In this study we examined changes in muscle tissue in a classic model of diabetes and hyperglycemia in rabbits to determine if similar dysregulation of Alzheimer Aβ peptides, the prion protein (PrP, and superoxide dismutase 1 (SOD1, as well as nitric oxide synthases is produced in muscle in diabetic animals. This wild-type rabbit model includes systemic physiological expression of human-like Alzheimer precursor proteins and Aβ peptides that are considered key in Alzheimer protein studies. Results Diabetes was produced in rabbits by injection of the toxic glucose analogue alloxan, which selectively enters pancreatic beta cells and irreversibly decreases insulin production, similar to streptozotocin. Quadriceps muscle from rabbits 16 wks after onset of diabetes and hyperglycemia were analyzed with biochemical and in situ methods. Immunoblots of whole muscle protein samples demonstrated increased PrP, SOD1, as well as neuronal and inducible Nitric oxide synthases (NOS1 and NOS2 in diabetic muscle. In contrast, we detected little change in Alzheimer Aβ precursor protein expression, or BACE1 and Presenilin 1 levels. However, Aβ peptides measured by ELISA increased several fold in diabetic muscle, suggesting a key role for Aβ cleavage in muscle similar to Alzheimer neurodegeneration in this diabetes model. Histological changes in diabetic muscle included localized accumulations of PrP, Aβ, NOS1 and 2, and SOD1, and evidence of increased central nuclei and cell infiltration. Conclusions The present study provides evidence that several classic amyloid and oxidative stress-related disease proteins coordinately increase in overall expression and form localized accumulations in diabetic muscle. The present study

  7. [Nitric oxide].

    Science.gov (United States)

    Rovira, I

    1995-01-01

    Nitric oxide was identified as the relaxing factor derived from the endothelium in 1987. Nitric oxide synthesis allows the vascular system to maintain a state of vasodilation, thereby regulating arterial pressure. Nitric oxide is also found in platelets, where it inhibits adhesion and aggregation; in the immune system, where it is responsible for the cytotoxic action of macrophages; and in the nervous system, where it acts as neurotransmitter. A deficit in endogenous synthesis of nitric oxide contributes to such conditions as essential arterial hypertension, pulmonary hypertension and heart disease. An excess of nitrous oxide induced by endotoxins and cytokinins, meanwhile, is believed to be responsible for hypotension in septic shock and for hyperdynamic circulatory state in cirrhosis of the liver. Nitric oxide has also been implicated in the rejection of transplanted organs and in cell damage after reperfusion. Inhaled nitrous oxide gas reduces pulmonary hypertension without triggering systemic hypotension in both experimental and clinical conditions. It also produces selective vasodilation when used to ventilate specific pulmonary areas, thereby improving the ventilation/perfusion ratio and, hence, oxygenation. Nitric oxide inhalation is effective in pulmonary hypertension-coincident with chronic obstructive lung disease, in persistent neonatal pulmonary hypertension and in pulmonary hypertension with congenital or acquired heart disease. Likewise, it reduces intrapulmonary shunt in acute respiratory failure and improves gas exchange. Under experimental conditions nitric oxide acts as a bronchodilator, although it seems to be less effective for this purpose in clinical use.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. 糖尿病大鼠心肌降钙素基因相关肽下调与心肌缺血/再灌注损伤加剧相关性研究%Study on the association of down-regulation of calcitonin gene-related peptide in myocardium with exaggerated myocardial injury after ischemia/reperfusion in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    李兔平; 刘超杰; 郭政

    2015-01-01

    目的 探讨糖尿病大鼠心肌降钙素基因相关肽(calcitonin gene-related peptide,CGRP)的变化与糖尿病心肌易损性增加的相关性. 方法 180 g~200 g雄性Sprague-Dawley(SD)大鼠40只,采用随机数字表法分为两组:正常组(C组)和糖尿病组(DM组),每组20只.DM组采用高糖高脂饲料喂养,C组采用基础饲料喂养.在高糖高脂饲料喂养的第4周,采用小剂量(30 mg/kg)链脲佐菌素(streptozocin,STZ)腹腔注射建立糖尿病DM模型.注射STZ 10周后将DM组和C组采用随机数字表法分为糖尿病缺血/再灌注(ischemia/reperfusion,I/R)组(DM+I/R组)、糖尿病假手术组(DM +Sham组)、正常I/R组(C+I/R组)、正常假手术组(C+Sham组),每组10只.采用结扎冠状动脉左前降支的方法制备心肌I/R模型,采用免疫荧光技术和酶联免疫吸附法(enzyme-linked immuno sorbent assay,ELISA)对CGRP的表达进行定量分析,采用伊文蓝(evans blue,EB)与氯化三苯基四氮唑(triphenyltetrazolium chloride,TTC)染色的方法测量心肌缺血区及梗死区面积. 结果 心肌组织内CGRP免疫反应阳性神经纤维多见于心外膜和心肌层,尤其是血管周围及血管内皮.DM+Sham组心肌CGRP含量[(2 271±339)ng/g]显著低于C+Sham组[(4 369±310) ng/g](P<0.05).经过I/R后,虽然糖尿病大鼠与非糖尿病大鼠心肌组织中CGRP含量均比假手术组显著上调(P<0.05),但DM+I/R组心肌CGRP量[(3 138±423) ng/g]显著低于C+I/R组[(6 192±406) ng/g] (P<0.05).DM+I/R组心肌梗死面积(62.79%)显著大于C+I/R组(43.35%)(P<0.01). 结论 糖尿病导致心肌组织内感觉神经肽CGRP显著减少,该变化可能与糖尿病大鼠心脏I/R损伤加剧有关,相关的机制需进一步研究.%Objective The aim of the study was to investigate the association of change of calcitonin gene-related peptide (CGRP) in myocardium with increase of myocardial vulnerability in diabetic rats.Methods Forty male Sprague-Dawley(SD) rats,weighing 180 g-200

  9. 实验性结肠炎对脊髓传入神经元中降钙素基因相关肽和香草酸受体1表达的调节%Effects of experimental colitis on the expressions of calcitonin gene-related peptide and vanilloid receptor 1 in rat spinal cord sensory neurons

    Institute of Scientific and Technical Information of China (English)

    杨霞; 韩俊庆; 刘然

    2008-01-01

    本文旨在探讨肠道局部炎症对脊髓肠道感觉传入神经通路的近期及远期效应,应用三硝基苯磺酸(trinitrobenzenesulfonic acid,TNBS)建立大鼠结肠炎动物模型,用DiI(3)逆行神经标记法识别支配肠道炎症部位的脊髓背根神经节(dorsalrootganglia,DRG)神经元,通过肉眼观察、平均组织损伤评分及髓过氧化物酶活性测定等方法评价肠道组织的炎症反应状态,用免疫组织化学法测定香草酸受体l(vanilloid receptor 1,VRl)和降钙素基因相关肽(calcitonin gene-related peptide,CGRP)在支配结肠炎症部位的DRG神经元中的表达,比较炎症不同阶段(给予TNBS后7、21、42 d)CGRP和VRI阳性神经元的数目.结果显示,炎症急性期(即给予TNBS后7 d)结肠黏膜肉眼可见明显损伤,同时相应DRG中表达CGRP及VRl的神经元增加近2倍[(95.38±9.45)%VS(42.86±5.02)%,(89.23±8.21)%VS(32.54±4.58)%].给予TNBS后21、42 d,肠道炎症反应已完全消退,但表达CGRP及VRl的DRG神经元数目仍明显高于对照组[(86.25±8.21)%,(68.28±7.12)%VS(42.86±5.02)%;(67.22±6.52)%,(56.25±4.86)%VS(32.54±4.58)%].结果提示,肠道局部炎症可以上调支配肠道的脊髓传入神经元中CGRP和VRl的表达,这种异常表达可以持续至肠道炎症反应消退后的一定时间.%To study the acute and long-term effects of local gut infammation on the sensitivity of the spinal sensory neurons,the expressions of vanilloid receptor 1(VR1)and calcitonin gene-related peptide(CGRP)in the colon-innervated primary sensory neurons in dorsal root ganglia(DRG)were examined in rats with trinitrobenzenesulfonic acid(TNBS)-induced experimental colitis.The neurons projecting to the distal colon were identified by DiI(3)retrograde labelling.Macroscopic examination,mean damage score and myeloperoxidase(MPO)activity were determined to assess the inflammatory status of the colon tissue.The number of CGRP and VR1 immunoreactive neurons at different stages of

  10. Argininosuccinate synthetase is a functional target for a snake venom anti-hypertensive peptide: role in arginine and nitric oxide production.

    Science.gov (United States)

    Guerreiro, Juliano R; Lameu, Claudiana; Oliveira, Eduardo F; Klitzke, Clécio F; Melo, Robson L; Linares, Edlaine; Augusto, Ohara; Fox, Jay W; Lebrun, Ivo; Serrano, Solange M T; Camargo, Antonio C M

    2009-07-24

    Bj-BPP-10c is a bioactive proline-rich decapeptide, part of the C-type natriuretic peptide precursor, expressed in the brain and in the venom gland of Bothrops jararaca. We recently showed that Bj-BPP-10c displays a strong, sustained anti-hypertensive effect in spontaneous hypertensive rats (SHR), without causing any effect in normotensive rats, by a pharmacological effect independent of angiotensin-converting enzyme inhibition. Therefore, we hypothesized that another mechanism should be involved in the peptide activity. Here we used affinity chromatography to search for kidney cytosolic proteins with affinity for Bj-BPP-10c and demonstrate that argininosuccinate synthetase (AsS) is the major protein binding to the peptide. More importantly, this interaction activates the catalytic activity of AsS in a dose-de pend ent manner. AsS is recognized as an important player of the citrulline-NO cycle that represents a potential limiting step in NO synthesis. Accordingly, the functional interaction of Bj-BPP-10c and AsS was evidenced by the following effects promoted by the peptide: (i) increase of NO metabolite production in human umbilical vein endothelial cell culture and of arginine in human embryonic kidney cells and (ii) increase of arginine plasma concentration in SHR. Moreover, alpha-methyl-dl-aspartic acid, a specific AsS inhibitor, significantly reduced the anti-hypertensive activity of Bj-BPP-10c in SHR. Taken together, these results suggest that AsS plays a role in the anti-hypertensive action of Bj-BPP-10c. Therefore, we propose the activation of AsS as a new mechanism for the anti-hypertensive effect of Bj-BPP-10c in SHR and AsS as a novel target for the therapy of hypertension-related diseases.

  11. 不同给药方式下降钙素基因相关肽在蛛网膜下腔出血大鼠的组织分布%Tissue distribution of calcitonin gene-related peptide administered via different routes in rats with subarachnoid hemorrhage

    Institute of Scientific and Technical Information of China (English)

    吴庆建; 孙树印; 宋大庆; 张颜波; 闫承军; 孙保亮

    2015-01-01

    Objective To investigate the tissue distribution of calcitonin gene-related peptide (CGRP) by nasal versus intravenous administrations in rats with subarachnoid hemorrhage (SAH).Methods The SAH rat model was established by injecting fresh autologous arterial blood into cisterna magna twice.Sixty-four rats were divided into 4 groups by random digit table:(1) group A (n=16):the normal rats were treated with 125I marked CGRP (125I-CGRP) by nasal administration;(2) group B (n=16):the SAH model rats were treated with 125I-CGRP by nasal administration;(3) group C (n=16):the normal rats were treated with 125I-CGRP via femoral vein;(4) group D (n=16):the SAH model rats were treated with 125I-CGRP via femoral vein.The tissue distribution of CGRP in rats of each group at 30 min after the treatment was compared by radioisotope tracing.Results The CGRP concentrations of brain regions,spinal cord,and cerebrospinal fluid (CSF) in normal rats and SAH model rats by nasal administration of 125I-CGRP were significantly higher than those by intravenous administration;whereas the CGRP concentrations of blood,thyroid,deep cervical lymph nodes,liver and lung tissues in normal rats and SAH model rats by nasal administration of 125I-CGRP were significantly lower than those by intravenous administration (all P<0.05).After nasal administration,the CGRP concentration in the olfactory bulb was the highest,followed by those in CSF and spinal cord.Conclusion Tissue distribution of CGRP differs between nasal administration and intravenous administration.Nasal administration of CGRP shows significant advantages in the medical treatment for disorders of the central nervous system.%目的 探讨经鼻给药、经静脉给药降钙素基因相关肽(CGRP)在蛛网膜下腔出血(SAH)大鼠的组织分布.方法 采用枕大池两次注入新鲜自体动脉血的方法建立SAH大鼠模型,64只大鼠按随机数字表法分为4组:(1)A组(n=16):经鼻给予125I标记的CGRP(125I

  12. Effect of Drug Pair of Coptis Chinensis and Evodia Rutatecarpa on Blood Pressure,Plasma Endothelin and Calcitonin Gene - related Peptide in Spontaneous Hypertension Rats%药对黄连、吴茱萸对高血压大鼠血压和血浆ET、CGRP的影响

    Institute of Scientific and Technical Information of China (English)

    卜宪峥; 吴华芹; 胡元会; 褚瑜光; 宋庆桥; 王师菡

    2011-01-01

    Objective To investigate the effects of drug pair of coptis chinensis and evodia rutatecarpa on blood pressure.the content of plasma endothelin(ET) .and calcitonin gene - related peptide (CGRP) in spontaneous hypertension rats(SHR). Methods Twenty - four SHR were randomly divided into model group(n = 8) .nifedipine group(n = 8) given nifedipine .and Lianyu decoction group(w=8) given Lianyu oral liquid by continuously gavages. Eight normal Wistar - Kyoto rats(WKY) were as control (WKY group). WKY group and Model group were given normal saline. After treatment for 4 weeks* blood pressure,the content of plasma ET and CGRP were measured. Results Compared with model group, the blood pressure in Lian - Yu decoction group was significantly lower (P<0. 01). The content of ET was decreased (P<0. 05) .while the content of plasma CGRP was greatly increased (P<0. 01) in Lianyu decoction group. Conclusion Drug pair of coptis chinensis and evodia rutatecarpa could significantly reduce blood pressure in SHR, which might be related to reduce the content of plasma ET and increase the content of plasma CGRP.%目的 观察药对黄连、吴茱萸对自发性高血压大鼠(SHR)血压和血管活性物质内皮素(ET)、降钙素基因相关肽(CGRP)含量的影响.方法将24只SHR随机分为模型组(Model组)、硝苯地平组(Nif组)、连萸药对组(LY组),每组8只,以正常WKY大鼠为对照组(WKY组),8只,共4组.WKY组和Model组予以生理盐水,Nif组予以硝苯地平溶液,中药组予以相应配伍剂量的浓煎剂,连续灌胃4周,测量大鼠灌胃前和灌胃4周末大鼠尾动脉的收缩压.第4周末同时测定大鼠血浆中ET、CGRP的含量.结果 与Model组比较,中药组大鼠4周后血压水平明显降低(P<0.05),血浆ET含量降低(P<0.05),CGRP的含量明显升高(P<0.05),但与Nif组相比无统计学意义.结论 药对黄连、吴茱萸对SHR有明显的降压作用,其机制可能与降低血浆中ET的含量,增加CGRP的含量有关.

  13. 普瑞巴林对原发性三叉神经痛患者血浆 P物质和降钙素基因相关肽的影响%Influence of Pregabalin on plasma substance P and calcitonin gene-related peptide in patients with trigeminal neuralgia

    Institute of Scientific and Technical Information of China (English)

    熊勋波; 杨涛; 邓刚; 成祥林; 向明清; 刘焰

    2014-01-01

    目的::观察普瑞巴林( PGB )和卡马西平( CBZ )对原发性三叉神经痛( PTN )患者血浆 P 物质( SP )和降钙素基因相关肽( CGRP)以及疼痛视觉模拟评分( VAS)的影响,评估PGB治疗PTN的疗效和安全性。方法:130例PTN患者随机分为观察组64例使用PGB治疗,对照组66例使用CBZ治疗。分别从低剂量开始给药,观察患者的疗效及不良反应至第4周末,两组患者在治疗前和结束时以放免法测定血浆SP和CGRP含量,并进行VAS评分。结果:观察组患者的总有效率89.1%,对照组72.1%,两组患者差异有统计学意义(P<0.05);治疗后两组患者的血浆SP和CGRP均下降,观察组患者较对照组尤为明显(P<0.05)。观察组不良反应发生率31.3%明显低于对照组59.1%。结论:PGB治疗PTN疗效和安全性均高于CBZ。%Objective:To observe influence of Pregabalin ( PGB) and Carbamazepine ( CBZ) on plasma substance P ( SP) , calcitonin gene-related peptide ( CGRP) , and pain visual analogue score ( VAS) for patients with trigeminal neuralgia ( PTN) , and e﹣valuate efficacy and safety of PGB in treatment of PTN. Methods:130 patients with PTN were randomly divided into observation group ( PGB, 64 cases) and control group ( CBZ, 66 cases) . Both groups were administered with low dose at first, and then the therapeutic effect and adverse effect until termination of the fourth week were observed. The plasma SP and CGRP were detected by radioimmuno﹣assay before and after the treatment, while the visual analogue scales ( VAS) were measured. Results:The clinical efficiency of PGB was 89. 1%, that of CBZ was 72. 1%, and there was a significant difference between the two groups (P<0. 05). The treatments re﹣duced plasma SP and CGRP levels in both groups, and the change of PGB group was more obvious than that of CBZ group (P<0. 05). The incidence rate of adverse effect by PGB (31. 3%) was less than that by CBZ (59. 1%) (P<0. 05). Conclusions

  14. Peptídeo relacionado ao gene da calcitonina por iontoforese na viabilidade de retalho cutâneo randômico em ratos Calcitonin gene-related peptide by iontophoresis on the viability of the randon skin flaps in rats

    Directory of Open Access Journals (Sweden)

    Ivaldo Esteves Junior

    2004-12-01

    Full Text Available Objetivo: Investigar o efeito da administração tópica do peptídeo relacionado ao gene da calcitonina (CGRP por iontoforese na viabilidade de retalho cutâneo randômico em ratos. Métodos: Sessenta ratos Wistar EPM-1, adultos e machos foram submetidos a retalho cutâneo randômico. Os animais foram distribuídos aleatoriamente em quatro grupos. Nos animais do grupo 1 (controle, n=15 realizou-se simulação de estímulo elétrico, no grupo 2 (iontoforese placebo, n=15 os animais foram submetidos à corrente contínua, no grupo 3 (controle de absorção, n=15 os animais receberam simulação de estímulo elétrico com CGRP e, por fim os animais do grupo 4 (tratado, n=15 foram tratados com iontoforese de CGRP. Em todos os grupos estes procedimentos foram realizados imediatamente após a técnica operatória e nos dois dias subsequentes. A porcentagem da área de necrose foi avaliada no sétimo dia de pós-operatório. Resultados: A média das porcentagens das áreas de necrose foram: grupo 1- 48%, grupo 2 - 51%, grupo 3 - 46% e, grupo 4 - 28%. A análise estatística, através do teste de Kruskal-Wallis, evidenciou diferença significante (pPurpose: Assess the effect of the local administration of calcitonin gene-related peptide (CGRP by iontophoresis on the viability of random skin flap in rats. Methods: Sixty Wistar-EPM 1 rats were submitted to dorsal skin flap of cranial base 10 x 4 cm with interposition of a plastic barrier between the skin flap and the donnor site. The animals were randomly distributed in four groups (n = 15 in each group and were treated as follows: in group 1 (control, animals were submitted to a simulation of electrical current for 20 minutes; group 2, (iontophoresis placebo animals were submitted to direct current of 4mA amplitude for 20 minutes; group 3 (absorption control receive simulation of electrical current for 20 minutes with CGRP on one of the electrodes; group 4 (iontophoretically treated treated by

  15. Effect of gamma-aminobutyric acid treatment on plasma substance P and calcitonin gene-related peptide levels in children with asthma%γ-氨基丁酸治疗对哮喘患儿血浆P物质和降钙素基因相关肽含量的影响

    Institute of Scientific and Technical Information of China (English)

    徐传伟; 郭山春; 郑振文; 王庆元

    2013-01-01

    目的 探讨γ-氨基丁酸(GABA)治疗前后哮喘患儿血浆P物质(SP)和降钙素基因相关肽(CGRP)含量的变化.方法 75例哮喘患儿随机分为GABA治疗组(36例)和对照组(39例),两组患儿均给予哮喘常规治疗.治疗组在常规治疗的基础上给予GABA口服(每日25 ~ 30 mg/kg).采用酶联免疫吸附法(ELISA)测定患儿治疗前、缓解后血浆SP、CGRP的含量.结果 两组患儿治疗前血浆SP、CGRP含量差异无统计学意义(P>0.05);哮喘缓解后治疗组血浆SP、CGRP含量分别为57±15 pg/mL、23±10 pg/mL,显著低于对照组(分别为127±12 pg/mL、42 ±8 pg/mL),差异有统计学意义(P<0.01).两组哮喘缓解后血浆SP、CGRP含量均较治疗前明显下降,差异有统计学意义(P<0.01).哮喘患儿血浆SP与CGRP含量呈显著正相关(r=0.792,P<0.01).结论 GABA可抑制小儿哮喘急性发作期血浆SP、CGRP的释放.%Objective To study the changes in plasma substance P (SP) and calcitonin gene-related peptide (CGRP) levels in children with acute asthma before and after gamma-aminobutyricacid (GABA) treatment. Methods Seventy-five children with asthma were randomly assigned to GABA treatment ( n = 36 ) and control groups ( n = 39 ) . Both groups were given conventional treatment for asthma. Besides the conventional treatment, the treatment group was administered with oral GABA (25 - 30 mg/kg·d). Plasma content of SP and CGRP was measured using ELISA before treatment and after remission. Results There were no significant differences in plasma content of SP and CGRP between the GABA treatment and control groups (P > 0.05) before treatment. Plasma content of SP and CGRP in the GABA treatment group was significantly lower than the control group (SP: 57 ± 15 pg/mL vs 127 ± 12 pg/mL; CGRP: 23 ± 10 pg/mL vs 42 ± 8 pg/mL) after remission (P<0. 01). Plasma content of SP and CGRP after remission was significantly lower than before treatment (P <0.01) in both groups. There was a

  16. Effects of xenotransplantation of microencapsulated sciatic nerve tissue cells on the expression of calcitonin gene-related peptide after spinal cord injury in rats%异种细胞移植对大鼠损伤脊髓降钙素基因相关肽表达的影响

    Institute of Scientific and Technical Information of China (English)

    段平国; 孙贵才; 刘德明

    2011-01-01

    Objective: To observe the effects of xenotransplantation of the microencapsulated sciatic nerve tissue/cella on the expression of calcitonin gene-related peptide (CGRP) after spinal cord injury (SCI) in rats.Methods: Bilateral sciatic nerves of rabbits were preconditioned for 1 week were dissected under sterile conditions and made into nerve tissue/cells suspension which was mixed with 1.5% sodium alginate solution.The mixture was then extruded using a droplet generation device into 20 mmol/L barium chloride solution to form barium-alginate capsules.Microencapsulated nerve tissue/cells suspension was implanted into the injured sites of the spinal cord in rats.By immunohistochernstry, the expressions of CGRP were observed.Results: The number of CGRP-positive cells in the right ventral horn of spinal cord of rats reduced remarkably in each group after SCI, and it gradually recovered in varying degrees 1 week later.The difference of the number of CGRP-positive cells between the microcapsule group and the cell group was not remarkable, but both of them existed in the distinction when compared with the injury group (P <0.05).At 2, 4 weeks and 8 weeks after SCI, compared to the cell group and injury group,the number of CGRP-positive cells in the microcapsule group increased obviotrsly.Conclusion: The xenotransplantation of the microencapsulated sciatic nerve tissue/cells promotes the expression of CGRP after SCI in rats, benefiting the regeneration of neuron.%目的:观察微囊化异种坐骨神经组织细胞移植对脊髓损伤大鼠降钙素基因相关肽(CGRP)表达的影响.方法:取家兔预变性处理1周的坐骨神经制成组织细胞悬液,与1.5%海藻酸钠溶液混合并喷入20mmol/L氯化钡溶液中制成微囊化的组织细胞悬液.将其植入SD大鼠脊髓损伤处,通过免疫组织化学显色观察CGRP的表达情况.结果:SCI后各组大鼠右侧脊髓前角CGRP阳性细胞数减少,1周后均不同程度地逐渐恢复.SCI后1周,细

  17. The protective effect of calcitonin gene-related peptide on gastric mucosa injury after cerebral ischemia reperfusion in rats%大鼠脑缺血再灌注后降钙素基因相关肽对受损胃黏膜的保护作用

    Institute of Scientific and Technical Information of China (English)

    冯国营; 许晓博; 王迁

    2009-01-01

    @@ The purpose of the present study is to investigate the protective effect of calcitonin gene-related pepfide (CGRP) on gastric mucosa injury after focal cerebral ischemia reperfusion and gastric ischemia-reperfusion in rats. Wistar male rats (280-320g) were selected for this experiment. Focal cerebral ischemia and reperfusion rat model was established with left middle cerebral artery occlusion by using thread inserting.

  18. 神经肽P物质、降钙素基因相关肽在膝骨性关节炎软骨下骨中的表达%Neuropeptides substance P and calcitonin gene related peptide expression in knee osteoarthritis ;subchondral bone

    Institute of Scientific and Technical Information of China (English)

    付昌马; 杨祖华

    2014-01-01

    Objective To study the expression of neuropeptide substance P (SP) and calcitonin gene related peptide (CGRP) in the subchondral bone patients with knee osteoarthritis (OA). Methods A total 40 patients with OA were used as study group, and 10 patients with lower femur fractures were used as control group. Immunohistochemical staining were used to analyze neuropeptides SP and CGRP positive expression in 40 cases OA patients and 10 cases lower femur fractures patients. Results (1) The number of neuropeptide SP positive cells (2.62±0.31 vs. 1.58±0.32, P<0.05) and neuropeptide CGRP positive cells (2.58±0.23 vs. 1.55±0.25, P<0.05) was significantly higher in OA group than control group. (2) Neuropeptide SP average optical density(0.345±0.031 vs. 0.224±0.072, P<0.05) and neuropeptide CGRP average optical density(0.585±0.043 vs. 0.326±0.065, P<0.05) was significantly higher in OA group than control group. (3) Neuropeptide CGRP average optical density (0.585±0.043) was higher than the average optical density of SP (0.345±0.031) (P<0.05) in OA group. Conclusion Significantly higher neuropeptide SP and CGRP levels were found in patients with OA;neuropeptide expression leading to bone metabolic imbalance, adjustment disorder with cycles occur within the joint, and thus play a role in OA group.%目的:研究证明含有神经肽 P 物质(SP)、降钙素基因相关肽(CGRP)共同存在于膝骨性关节炎(OA)中,本研究验证这些肽能神经在膝OA发病中可能起作用。探讨膝OA患者软骨下骨中神经肽SP、 CGRP的表达及临床意义。方法收集2010年4月至2013年9月在合肥市第三人民医院治疗的40例膝OA患者及10例股骨下段骨折患者临床资料。免疫组化染色检测40例膝OA患者(OA组)及10例股骨下段骨折患者(正常对照组)软骨下骨组织神经肽SP、 CGRP的阳性表达。结果(1)40例膝OA患者与10例正常对照组比较,神经肽SP的阳性细胞表达数(2.62

  19. Sugarcane genes related to mitochondrial function

    Directory of Open Access Journals (Sweden)

    Fonseca Ghislaine V.

    2001-01-01

    Full Text Available Mitochondria function as metabolic powerhouses by generating energy through oxidative phosphorylation and have become the focus of renewed interest due to progress in understanding the subtleties of their biogenesis and the discovery of the important roles which these organelles play in senescence, cell death and the assembly of iron-sulfur (Fe/S centers. Using proteins from the yeast Saccharomyces cerevisiae, Homo sapiens and Arabidopsis thaliana we searched the sugarcane expressed sequence tag (SUCEST database for the presence of expressed sequence tags (ESTs with similarity to nuclear genes related to mitochondrial functions. Starting with 869 protein sequences, we searched for sugarcane EST counterparts to these proteins using the basic local alignment search tool TBLASTN similarity searching program run against 260,781 sugarcane ESTs contained in 81,223 clusters. We were able to recover 367 clusters likely to represent sugarcane orthologues of the corresponding genes from S. cerevisiae, H. sapiens and A. thaliana with E-value <= 10-10. Gene products belonging to all functional categories related to mitochondrial functions were found and this allowed us to produce an overview of the nuclear genes required for sugarcane mitochondrial biogenesis and function as well as providing a starting point for detailed analysis of sugarcane gene structure and physiology.

  20. Distribution and source of calcitonin gene-related peptide immunoreactive nerve terminal in prepuce of penis and frenulum of prepuce of rats%大鼠阴茎包皮及包皮系带内降钙素基因相关肽免疫阳性神经末梢的分布与起源

    Institute of Scientific and Technical Information of China (English)

    吴仲敏; 王东红; 赵礼东; 凌树才; 朱晞

    2006-01-01

    树枝状或念珠状分布,大多成束走行,长短不一,有的呈结节状膨大.②阴茎系带处降钙素基因相关肽免疫阳性神经末梢的分布密度明显大于阴茎包皮处(2.15±0.32,1.02±0.22,t=-2.03,P<0.01).③结合荧光金逆行标记法研究发现,这些神经末梢起源于第6腰髓对应的背根神经节和第1骶髓对应的背根神经节的神经元.荧光金逆标阳性神经元大小不等,胞体呈圆形或卵圆形,未见明显的突起,胞浆内有明亮的金黄色细小颗粒,胞核无标记.细胞大多沿神经束成行排列或散在分布.进一步作降钙素基因相关肽免疫荧光标记后发现降钙素基因相关肽单标阳性神经元大多为中小型细胞,染色较深,反应产物均匀分布于胞浆内,呈明亮的深绿色(FITC标记色).在不同激发光下对照观察同一张阳性切片,发现荧光金/降钙素基因相关肽双标阳性细胞均为中小型,其数量占荧光金逆行标记阳性细胞总数的二分之一.结论:降钙素基因相关肽可能参与大鼠阴茎包皮以及包皮系带感觉信息的传递.大鼠阴茎包皮系带内降钙素基因相关肽免疫阳性神经末梢源自于第6腰髓对应的背根神经节和第1骶髓对应的背根神经节的神经元.%BACKGROUND: Frenulum of prepuce of penis contained many nerve terminals is an extremely sensitive region. If the frenulum is injured in circumcision or other operations, the complication, such as postoperative spontaneous pain of penis, sexual disturbance and so on, will occur. But there still is no define explanation for this up to now.OBJECTIVE: To observe the distribution of immunoreactive nerve terminal of calcitonin gene-related peptide (CGRP) in prepuce of penis and frenulum of prepuce of adult SD rats, and look for the source of CGRP immunoreactive nerve terminal in frenulum of prepuce.DESIGN: A single sample trial.SETTING:Department of Anatomy, School of Medicine, Zhejiang University.MATERIALS: The

  1. Relationship between Visceral Hyperalgesia in Developing Rats and Expression of Calcitonin Gene-Related Peptide in Different Regions of Brain%幼鼠内脏痛高敏感性与不同脑区降钙素基因相关肽表达的关系

    Institute of Scientific and Technical Information of China (English)

    陈素清; 吴斌; 林希; 杨燕珍

    2011-01-01

    目的 采用新生期伤害性结直肠刺激(CI)建立幼鼠痛高敏感模型,检测痛觉敏感幼鼠模型下丘脑室旁核、中缝核和前皮质扣带回内降钙素基因相关肽(CGRP)的分布和表达,探讨不同脑区CGRP异常表达参与痛觉高敏感形成的可能机制.方法 8日龄新生SD大鼠分为4组,每组8只.CI+CRD组新生期给予CI,并在6周龄时给予结直肠扩张(CRD)刺激;CI组新生期给予CI,但在6周龄时不予CRD刺激;CRD组新生期不予CI,6周龄时给予CRD刺激;对照组新生期不予CI,6周龄时也未给予CRD刺激.CI+CRD组和CI组乳鼠在出生8~15 d,每天接受1次CI.常规喂养至6周龄,CI+CRD组和CRD组幼鼠进行CRD刺激下内脏痛敏感性评价.采用SABC免疫组织化学法检测4组幼鼠不同脑区内CGRP表达情况.结果 随着CRD的增加,CI+CRD组和CRD组幼鼠腹外斜肌放电波幅逐渐增加.在CRD为2 kPa、4 kPa、6 kPa和8 kPa扩张压刺激下,CI+CRD组腹外斜肌放电幅值显著高于CRD组,差异有统计学意义(F=43.261,P=0.000;F=15.389,P=0.002;F=8.024,P=0.013;F=6.287,P=0.025).而当CRD为10 kPa高扩张压刺激时,CI+CRD组和CRD组腹外斜肌放电幅值差异无统计学意义(F=0.502,P=0.490).新生期CI导致幼鼠下丘脑室旁核、前扣带回皮质、中缝核内CGRP阳性细胞数明显增加的主效应分别为12.23、12.74和11.81,接受CRD刺激后可导致幼鼠CGRP阳性细胞数明显增加的主效应分别为16.81、18.00和17.18.结论 新生期持续CI会造成幼鼠痛阈下降,出现慢性内脏痛高敏感性.幼鼠慢性内脏痛敏感性异常可能与前皮质扣带回、下丘脑室旁核、中缝核内CGRP异常表达相关.CGRP可能作为一种神经递质参与内脏痛觉敏感的改变.%Objective To establish the model of visceral hyperalgesia in developing rats by colorectal irritation ( CI), detect the distribution and expression of calcitonin gene - related peptide(CGRP) in hypothalamus paraventricular nucleus

  2. Triptan-induced enhancement of neuronal nitric oxide synthase in trigeminal ganglion dural afferents underlies increased responsiveness to potential migraine triggers.

    Science.gov (United States)

    De Felice, Milena; Ossipov, Michael H; Wang, Ruizhong; Dussor, Gregory; Lai, Josephine; Meng, Ian D; Chichorro, Juliana; Andrews, John S; Rakhit, Suman; Maddaford, Shawn; Dodick, David; Porreca, Frank

    2010-08-01

    Migraine is a common neurological disorder often treated with triptans. Triptan overuse can lead to increased frequency of headache in some patients, a phenomenon termed medication overuse headache. Previous preclinical studies have demonstrated that repeated or sustained triptan administration for several days can elicit persistent neural adaptations in trigeminal ganglion cells innervating the dura, prominently characterized by increased labelling of neuronal profiles for calcitonin gene related peptide. Additionally, triptan administration elicited a behavioural syndrome of enhanced sensitivity to surrogate triggers of migraine that was maintained for weeks following discontinuation of drug, a phenomenon termed 'triptan-induced latent sensitization'. Here, we demonstrate that triptan administration elicits a long-lasting increase in identified rat trigeminal dural afferents labelled for neuronal nitric oxide synthase in the trigeminal ganglion. Cutaneous allodynia observed during the period of triptan administration was reversed by NXN-323, a selective inhibitor of neuronal nitric oxide synthase. Additionally, neuronal nitric oxide synthase inhibition prevented environmental stress-induced hypersensitivity in the post-triptan administration period. Co-administration of NXN-323 with sumatriptan over several days prevented the expression of allodynia and enhanced sensitivity to stress observed following latent sensitization, but not the triptan-induced increased labelling of neuronal nitric oxide synthase in dural afferents. Triptan administration thus promotes increased expression of neuronal nitric oxide synthase in dural afferents, which is critical for enhanced sensitivity to environmental stress. These data provide a biological basis for increased frequency of headache following triptans and highlight the potential clinical utility of neuronal nitric oxide synthase inhibition in preventing or treating medication overuse headache.

  3. GLP-1对人脐静脉内皮细胞释放NO的影响及机制的研究%Effects and Mechanism of Glucagon like Peptide-1 on Nitric Oxide Release in Human Umbilical Vein Endothelial Cells

    Institute of Scientific and Technical Information of China (English)

    丁丽; 张绍维; 赵文洲; 罗晶; 王巍; 张锦

    2015-01-01

    Objective:To investigate the effects of glucagon-like peptide-1 (GLP-1) on nitric oxide (NO) release in human umbilical vein endothelial cells (HUVECs) and whether GLP-1 receptor (GLP-1R) and GLP-1 (9-36) are involved in mediating the effects.Methods:HUVECs were incubated in the presence or absence of GLP-1,exenatide (a GLP-1R agonist) or GLP-1 (9-36),or incubated in the presence of GLP-1 with or without exendin (9-39) (a GLP-1R antagonist) and/or sitagliptin (inhibitting formation of GLP-1 [9-36]).NO content in the cell culture medium was measured by adopting nitrate reductase method.Results:GLP-1 dose-dependently promoted NO release in HUVECs.Exenatide and GLP-1 (9-36) both increased NO release.Exendin (9-39) and sitagliptin both partly blocked the effects of GLP-1.Conclusion:GLP-1 may have directly protective effect on endothelium by increasing NO release in HUVECs through GLP-1 R-dependent and GLP-1 (9-36)-related pathways.%目的:观察胰高糖素样肽-1(GLP-1)对脐静脉内皮细胞(HUVECs)释放一氧化氮(NO)的影响,并探讨GLP-1受体及GLP-1(9-36)在其中的作用.方法:分别以GLP-1、艾塞那肽、GLP-1 (9-36)、GLP-1+exendin(9-39)、GLP-1+西格列汀、GLP-1+西格列汀+exendin(9-39)孵育HUVECs,取培养上清以硝酸还原酶法检测NO浓度.结果:GLP-1剂量依赖性的增加HUVECs中NO释放,艾塞那肽和GLP-1 (9-36)均可刺激NO释放,exendin(9-39)和西格列汀均可部分阻断GLP-1引起的NO释放.结论:GLP-1可能通过GLP-1受体及GLP-1 (9-36)相关的途径刺激HUVECs NO释放,发挥直接的血管保护作用.

  4. Intermedin in paraventricular nucleus attenuates sympathetic activity and blood pressure via nitric oxide in hypertensive rats.

    Science.gov (United States)

    Zhou, Ye-Bo; Sun, Hai-Jian; Chen, Dan; Liu, Tong-Yan; Han, Ying; Wang, Jue-Jin; Tang, Chao-Shu; Kang, Yu-Ming; Zhu, Guo-Qing

    2014-02-01

    Intermedin (IMD) is a member of calcitonin/calcitonin gene-related peptide family, which shares the receptor system consisting of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMPs). This study investigated the effects of IMD in paraventricular nucleus (PVN) on renal sympathetic nerve activity and mean arterial pressure and its downstream mechanism in hypertension. Rats were subjected to 2-kidney 1-clip (2K1C) surgery to induce renovascular hypertension or sham operation. Acute experiments were performed 4 weeks later under anesthesia. IMD mRNA and protein were downregulated in 2K1C rats. Bilateral PVN microinjection of IMD caused greater decreases in renal sympathetic nerve activity and mean arterial pressure in 2K1C rats than in sham-operated rats, which were prevented by pretreatment with adrenomedullin receptor antagonist AM22-52 or nonselective nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester, and attenuated by selective neuronal NO synthase inhibitor N(ω)-propyl-l-arginine hydrochloride or endothelial NO synthase inhibitor N(5)-(1-iminoethyl)-l-ornithine dihydrochloride. AM22-52 increased renal sympathetic nerve activity and mean arterial pressure in 2K1C rats but not in sham-operated rats, whereas calcitonin/calcitonin gene-related peptide receptor antagonist calcitonin/calcitonin gene-related peptide 8-37 had no significant effect. CRLR and RAMP3 mRNA, as well as CRLR, RAMP2, and RAMP3 protein expressions, in the PVN were increased in 2K1C rats. Microinjection of IMD into the PVN increased the NO metabolites (NOx) level in the PVN in 2K1C rats, which was prevented by AM22-52. Chronic PVN infusion of IMD reduced, but AM22-52 increased, blood pressure in conscious 2K1C rats. These results indicate that IMD in the PVN inhibits sympathetic activity and attenuates hypertension in 2K1C rats, which are mediated by adrenomedullin receptors (CRLR/RAMP2 or CRLR/RAMP3) and its downstream NO.

  5. 受体成分蛋白在降钙素基因相关肽和血管紧张素Ⅱ对血管平滑肌细胞血管过氧化物酶1表达调控中的作用%Involvement of the receptor component protein in the regulation of vascular peroxidase-1 expression induced by calcitonin gene-related peptide and angiotensin Ⅱ in vascular smooth muscle cell

    Institute of Scientific and Technical Information of China (English)

    刘彦梅; 彭虹艳; 郭锋; 全海燕; 骆镜妃; 秦旭平

    2015-01-01

    血管紧张素Ⅱ (angiotensin Ⅱ,Ang Ⅱ)和降钙素基因相关肽(calcitonin gene-related peptide,CGRP)在血管的损伤和保护中起重要作用.为了探讨CGRP受体成分蛋白(receptor component protein,RCP)在CGRP和Ang Ⅱ对血管平滑肌细胞(vascularsmooth muscle cell,VSMC)血管过氧化物酶1(vascular peroxidase-1,VPO1)表达调控中的作用及机制,本研究采用体外培养鼠源性Al0血管平滑肌细胞株(A10VSMC),给予CGRP或/和Ang Ⅱ刺激,并用小干扰RNA (siRNA)干扰细胞RCP基因的表达,Western Blot检测RCP以及VPO1蛋白表达水平;RT-PCR检测RCP及VPO1 mRNA的表达水平.结果显示,在静止期野生型A10VSMC,CGRP和Ang Ⅱ能分别上调RCP和VPO1蛋白和mRNA表达(均P<0.05),但CGRP预孵育细胞后,Ang Ⅱ诱导的RCP和VPO1蛋白表达降低(均P<0.05);与野生型组比较,VPO1在所有RCP基因干扰组的表达均显著降低(均P<0.01).同时,在RCP基因干扰条件下,和对照组相比,CGRP处理组VPO1蛋白的表达显著增加,而Ang Ⅱ组没有明显变化;和Ang Ⅱ1组相比,CGRP与Ang Ⅱ联合作用显著增加VPOl蛋白表达,但这种作用能被抗氧化酶Catalase所抑制(P<0.05).以上结果提示,RCP可能参与CGRP或Ang Ⅱ诱导的VPO1蛋白表达;RCP可能在介导CGRP和Ang Ⅱ受体共同调控VPO1表达的信号转导整合中起一定作用.

  6. Effects of Duliang capsule on the expression of calcitonin gene-related peptide and cholecystokinin in the midbrain of a rat migraine model%都梁软胶囊对偏头痛模型大鼠中脑CGRP及CCK 表达的影响

    Institute of Scientific and Technical Information of China (English)

    韩喜梅; 姚刚; 满玉红; 于挺敏

    2016-01-01

    目的:研究都梁软胶囊对偏头痛模型大鼠中脑降钙素基因相关肽(CGRP)和缩胆囊肽(CCK)基因转录水平的影响,探讨其预防治疗偏头痛的作用机制。方法健康Wistar大鼠随机分4组,A为对照组,B为偏头痛组,C为都梁软胶囊对照组,D为都梁软胶囊治疗组。C、D组给予都梁软胶囊0.5g·kg -1·d-1灌胃,A、B组大鼠灌胃给予等量容积的 Tween‐80。灌胃7 d后,将B、D两组大鼠造硝酸甘油型偏头痛模型,造模2 h ,保存中脑标本。实时荧光定量PCR检测CGRP和CCK的转录水平。结果 D组大鼠中脑CGRP转录水平明显低于B组(0.64±0.35和1.61±0.51,P<0.05)。C组大鼠中脑CCK 转录水平明显低于A组(0.32±0.31和1.21±0.38,P<0.05)。结论都梁软胶囊可以干预中脑CGRP和CCK的表达,从而影响内源性痛觉调制系统的功能。%Objective To study the effects of Duliang capsule on the expression of calcitonin gene‐related peptide(CGRP) and cholecystokinin(CCK) in the midbrain of a rat migraine model ,and explored treatment effects and mechanisms of Duliang cap‐sule on rats with migraine .Methods A total of 24 rats were randomly divided into four groups :normal control groups(A) ,migraine model groups(B) ,Duliang capsule control groups(C) and Duliang capsule treatment groups(D) .C and D were intragastrically per‐fused with Duliang capsule(0 .5 g · kg -1 · d-1 ) .After 7 days ,nitroglycerin was subcutaneously injected into the buttocks of the B and D to induce migraine .Two hours after nitroglycerin injection ,the midbrain were isolated CGRP and CCK expression in midbrain were determined using SYBR Green I real‐time quantitative PCR .Results CGRP mRNA expression was significantly lower in mid‐brains of rats in the Duliang capsule treatment groups compared with migraine model groups(P<0 .05) .CCK mRNA expression was significantly lower in midbrains of rats in the

  7. Effects of intracerebroventricular morphine preconditioning on expression of calmodulin in hippocampus,calcitonin gene related peptide in plasma, substance P in hypothalamic paraventricular nucleus and myocardium in myocardial postischemia injury rats%中枢吗啡预处理对心脏缺血后大鼠海马CaM、血浆CGRP以及下丘脑室旁核和心肌P物质表达的影响

    Institute of Scientific and Technical Information of China (English)

    陆姚; 范礼斌; 张野; 翁立军; 李锐; 程新琦; 陈志武

    2009-01-01

    目的 探讨侧脑室内注射吗啡预处理对在体大鼠心肌缺血/再灌注损伤的影响及可能的信号机制.方法 建立模型大鼠,随机分为两个部分:①分为4组,每组6只:对照组(CON组),在缺血/再灌注前30 min内,侧脑室内微量泵注射0.9%生理盐水5 min,停止注射5 min,重复3次;预处理组(MPC组),在缺血/再灌注前30 min内,侧脑室内注射吗啡(1 μg·kg-1)5 min,停止5 min,重复3次;钙调蛋白抑制剂三氟拉嗪(trifluoperazine,TFP)+预处理组(TFP+MPC组),在吗啡预处理前10 min一次侧脑室内给予TFP(浓度为20 g·L-1)5 μl;另设TFP自身对照组(TFP组).②分为3组,每组6只:假手术组(Sham组),CON组和MPC组均同第一部分.观察指标包括:平均动脉压(MAP)、心率(HR),计算平均动脉压和心率乘积(RPP);心肌缺血危险区(AAR)、梗死区(IS)的体积、心肌梗死面积以IS/AAR表示;检测血浆降钙素基因相关肽(calcitonin gene related peptide, CGRP);测定海马组织钙调蛋白;测定下丘脑室旁核、心肌缺血区和非缺血区P物质的表达.结果与CON组相比,MPC组的IS和IS/AAR均明显下降(P0.05),而均明显高于MPC组(P<0.01);CON组分别与Sham组和MPC组相比,其下丘脑室旁核、心肌缺血区和非缺血区P物质表达均明显增高(P<0.01,P<0.05);MPC组血浆降钙素基因相关肽CGRP水平与海马钙调蛋白的表达均明显高于其它各组(P<0.01).结论 侧脑室内注射吗啡预处理对在体大鼠心肌缺血/再灌注损伤具有保护作用,其机制可能与钙调蛋白介导释放CGRP和痛觉的干预有关.

  8. 电刺激大鼠上矢状窦区硬脑膜后血浆与脑组织中降钙素基因相关肽、P物质和前列腺素 E2释放差异%Release difference of calcitonin gene-related peptide,substance P and prostaglandin E2 in orbital venous plexus plasma and brain tissues from rats with dura mater of superior sagittal sinus following electrical stimulation

    Institute of Scientific and Technical Information of China (English)

    陈健; 吕新勇; 孙晓萍; 陈春苗; 周军; 王振中; 萧伟

    2014-01-01

    OBJECTIVE Toexplorethefeasibilityofpreparingamigrainemodelusingratdura materofsuperiorsagittalsinusinfollowingelectricalstimulation.METHODS MaleSDratswereexposed to 1 h electrical stimulation after brain electrode implantation,at 3 V,6 Hz,and a pulse of 0.25 ms.At 0, 1 5,30 min,and 1 h,orbital blood and brain tissue were taken.The content of calcitonin gene-related peptide (CGRP),substance P and prostaglandin E2 (PGE2 )in the plas ma and brain tissue was detec-tedbyradioimmunoassay.RESULTS ThebraintissuecontentofCGRP,substancePandPGE2in the sham group and normal group was not significantly different.CGRP,substance P and PGE2 in brain tissue of model group were 3.41 ±0.93,1 .80 ±0.64,3.41 ±0.93 and (1 .80 ±0.64)ng·g -1 respec-tively,significantly different from sham group(P<0.05).At different time points,the content of CGRP, substance P and PGE2 in plasma orbital venous plexus showed no significant difference between sham groupandmodelgroup.CONCLUSION ThereleaseofCGRP,PGE2andsubstancePinbraintissue is significantly different fro m that of plas ma after electrical sti mulation.The results suggest that a model of migraine can be constructed by electrical stimulation.%目的:探讨电刺激大鼠上矢状窦区硬脑膜制备偏头痛模型的可行性。方法雄性SD 大鼠,脑部电极植入术后行电压3 V、频率6 Hz、脉宽0.25 ms、时间1 h电刺激,并于刺激0,15和30 min和1 h进行眼眶采血,采血后取脑组织。采用放射免疫法检测血浆和脑组织中降钙素基因相关肽(CGRP)、P物质和前列腺素E2(PGE2)含量。结果手术对照组与正常对照组大鼠脑组织中 CGRP 含量、P 物质含量和PGE2含量为均无显著性差异;模型组大鼠脑组织中CGRP、P物质和 PGE2分别为3.41±0.93,1.80±0.64和(5.17±0.69)ng·g -1,与手术对照组大鼠相比均有显著性差异(P<0.05)。各时间点手术对照组与模型组大鼠外周

  9. Differential sorting and packaging of capa-gene related products in an insect.

    Science.gov (United States)

    Pollák, Edit; Eckert, Manfred; Molnár, László; Predel, Reinhard

    2005-01-03

    A unique costorage of neuropeptides was recently found in the abdominal perisympathetic organs (PSOs) of the American cockroach, Periplaneta americana. Having specific antisera directed against all peptides belonging to this neurosecretory system, we examined the sorting of PSO-peptides in the soma of the median neurosecretory cells of abdominal ganglia by using immunoelectron microscopic double stainings. The data indicate that all six abundant neuropeptides of this neurohormonal system, which includes three capa-gene related products, are primarily incorporated into separate vesicles. These vesicles fuse with each other in the cytoplasm and become translucent on their way to the axon hillock. By means of light microscopy and MALDI-TOF mass spectrometry, an identical population of neuropeptides was found in interneurons of the brain. As revealed by subsequent immunoelectron microscopic analysis, the peptides of these cells are separately packed into dense core vesicles but do not fuse with each other. Thus, hitherto unknown cell-type-specific sorting mechanisms occur in neurosecretory cells and interneurons, respectively.

  10. Role of VEGF, Nitric Oxide, and Sympathetic Neurotransmitters in the Pathogenesis of Tendinopathy: A Review of the Current Evidences.

    Science.gov (United States)

    Vasta, Sebastiano; Di Martino, Alberto; Zampogna, Biagio; Torre, Guglielmo; Papalia, Rocco; Denaro, Vincenzo

    2016-01-01

    Chronic tendinopathy is a painful common condition affecting athletes as well as the general population undergoing to tendon overuse. Although its huge prevalence, little is known about tendinopathy pathogenesis, and even cloudier is its treatment. Traditionally, tendinopathy has been defined as a lack of tendon ability to overcome stressing stimuli with appropriate adaptive changes. Histologic studies have demonstrated the absence of inflammatory infiltrates, as a consequence conventional antinflammatory drugs have shown little or no effectiveness in treating tendinopathies. New strategies should be therefore identified to address chronic tendon disorders. Angiofibroblastic changes have been highlighted as the main feature of tendinopathy, and vascular endothelial growth factor (VEGF) has been demonstrated as one of the key molecules involved in vascular hyperplasia. More recently, attention has been focused on new peptides such as Substance P, nitric oxide, and calcitonin gene-related peptide (CGRP). Those new findings support the idea of a nerve-mediated disregulation of tendon metabolism. Each of those molecules could be a target for new treatment options. This study aimed to systematically review the current available clinical and basic science in order to summarize the latest evidences on the pathophysiology and its effect on treatment of chronic tendinopathy, and to spread suggestions for future research on its treatment.

  11. Role of VEGF, Nitric Oxide and sympathetic neurotransmitters in the pathogenesis of tendinopathy: a review of the current evidences

    Directory of Open Access Journals (Sweden)

    Sebastiano Vasta

    2016-08-01

    Full Text Available Chronic tendinopathy is a painful common condition affecting athletes as well as the general population undergoing to tendon overuse. Although its huge prevalence, little is known about tendinopathy pathogenesis, and even cloudier is its treatment.Traditionally, tendinopathy has been defined as a lack of tendon ability to overcome stressing stimuli with appropriate adaptive changes. Histologic studies have demonstrated the absence of inflammatory infiltrates, as a consequence conventional antinflammatory drugs have shown little or no effectiveness in treating tendinopathies. New strategies should be therefore identified to address chronic tendon disorders. Angiofibroblastic changes have been highlighted as the main feature of tendinopathy, and vascular endothelial growth factor (VEGF has been demonstrated as one of the key molecules involved in vascular hyperplasia. More recently, attention has been focused on new peptides such as Substance P, nitric oxide and calcitonin gene-related peptide. Those new findings support the idea of a nerve-mediated disregulation of tendon metabolism. Each of those molecules could be a target for new treatment options. This study aimed to systematically review the current available clinical and basic science in order to summarize the latest evidences on the pathophysiology and its effect on treatment of chronic tendinopathy, and to spread suggestions for future research on its treatment.

  12. Nitric oxide supersensitivity

    DEFF Research Database (Denmark)

    Olesen, J; Iversen, Helle Klingenberg; Thomsen, L L

    1993-01-01

    in a double blind design to 17 migraine patients, 17 age and sex matched healthy controls and 9 subjects with tension-type headache. The nitroglycerin-induced headache was significantly more severe in migraine sufferers, lasted longer and fulfilled diagnostic criteria for migraine more often. We have...... previously shown a similar supersensitivity to histamine which in human cerebral arteries activates endothelial H1 receptors and causes endothelial production of nitric oxide. Migraine patients are thus supersensitive to exogenous nitric oxide from nitroglycerin as well as to endothelially produced nitric...

  13. Effects of rizatriptan on calcitonin gene-related peptide, proenkephalin and cholecystokinin mRNA expressions in the trigeminal ganglia of a rat migraine model%利扎曲普坦对偏头痛大鼠三叉神经节降钙素基因相关肽和脑啡肽原及缩胆囊肽基因表达的影响

    Institute of Scientific and Technical Information of China (English)

    姚刚; 郝婷婷; 于挺敏

    2014-01-01

    Objective This study assesses the influence of rizatriptan on calcitonin gene-related peptide (CGRP),proenkephalin (PENK) and cholecystokinin (CCK) mRNA expressions in the trigeminal ganglia of a rat migraine model and investigates the possible mechanisms by which triptans treat migraine.Methods A total of 24 rats were randomly divided into four groups:normal control group (A),migraine model group(B),rizatriptan control group (C) and rizatriptan treatment group(D).Groups C and D were intragastrically perfused with rizatriptan,1 mg/kg per day.After 7 days,nitroglycerin was subcutaneously injected into the buttocks of the groups B and D to induce migraine.Two hours after nitroglycerin injection,the trigeminal ganglia was isolated.CGRP,PENK and CCK mRNA expressions in the trigeminal ganglia were determined using SYBR Green Ⅰ real-time quantitative PCR.Results The copy number of CGRP mRNA (× 107) in 200 ng total RNA of each group was 0.05 ±0.01,1.30 ±0.52,0.23 ±0.12,0.43 ±0.33 ; The copy number of PENK mRNA (× 103) in 200 ng total RNA of each group was 3.30 ± 1.65,0.34 ±0.14,3.91 ± 2.44,0.71 ± 0.13.The copy number of CGRP mRNA in the trigeminal ganglia of group B was significantly higher than that of group A (q =7.854,P < 0.05) ; CGRP mRNA expressions were significantly lower in the trigeminal ganglia of rats in group D compared with group B (q =5.458,P <0.05).Compared with group A,PENK mRNA expressions in the trigeminal ganglia of rats were significantly lower in group B (q =4.478,P < 0.05).PENK mRNA expressions were significantly higher in trigeminal ganglia of rats in group C compared with group D (q =4.838,P < 0.05).CCK mRNA expression in trigeminal ganglia of rats was similar among groups.Conelusions Rizatriptan can decrease the expressions of CGRP in the trigeminal ganglia of the migraine rats and exhibits neurogenic inflammation triggered by CGRP.PENK expressions decrease in the trigeminal ganglia of the migraine rats,weaken the analgesic

  14. Intermedin and calcitonin gene-related peptide fail to shine in acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    K.W. Morrice

    2014-11-01

    Methods and results: 81 patients admitted with suspected ACS were enrolled into the study. 50 were confirmed ACS by ACC (2000 guidelines and 31 were in a control group as non-cardiac chest pain. Intermedin was non-significantly elevated 6.14 pg/ml vs 4.84 pg/ml 8 h after pain onset. The degree of elevation will have limited clinical applicability.

  15. Study of Calcitonin and Calcitonin Gene-related Peptide in Patients with Medullary Thyroid Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ming Gao; Yang Yu; Shuling Li; Benyi Xu; Baocun Sun; Jingzu Liu

    2005-01-01

    OBJECTIVE To provide a basis for treatment and prognosis for MTC patients by investigating CT and CGRP.METHODS Fifty-eight cases of MTC were selected and the relationship between the CT levels and metastasis was investigated. An immunohistochemical method was used to detect the expression of CT and CGRP in the 58 samples of MTC tissues. The CT and CGRP of new MTC inpatients were measured before operation and in the first few days after operation using a radioimmunoassy.RESULTS 1 ) The metastatic rate of cervical lymph nodes was a significantly different between the normal serum CT group and the elevated group (P<0.01). 2) The rate of residual tumor was significantly different between the normal serum CT group one month after operation and the elevated group at the same period (P<0.01). 3) In the immunohistochemical study we found the positive rate of CT was about 98%, and the CGRP was 87.8%. 4) Part of the patients had an elevated CGRP level while CT levels were normal. 5) The serum CT levels dropped to a stable range one week after operation.CONCLUSION The CT levels are a useful index to evaluate the probability of cervical lymph node metastasis and the efficacy of surgical treatment.Measurement of the serum CGRP is an aid for the diagnosis of MTC,especially for those patients whose preoperative CT levels are normal.

  16. Increased circulating calcitonin in cirrhosis. Relation to severity of disease and calcitonin gene-related peptide

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Schifter, S; Møller, S

    2000-01-01

    circulating plasma concentrations of CT in patients with cirrhosis in relation to the severity of disease and the plasma level of CGRP. Moreover, the kinetics of CT was evaluated for different organ systems by determination of arteriovenous extraction. Thirty-nine patients with cirrhosis (Child-Turcotte...... control (12.1 v 6.9 pmol/L, P Turcotte score was found (P

  17. Blockade of calcitonin gene-related peptide release after superior sagittal sinus stimulation in cat

    DEFF Research Database (Denmark)

    Knight, Y E; Edvinsson, L; Goadsby, P J

    1999-01-01

    . Avitriptan and CP122,288 both have strong binding affinities for 5HT(1B/1D)receptors, but only CP122,288 is a potent inhibitor of PPE. In this study we sought to compare the effects of CP122,288 and avitriptan on jugular vein CGRP release after stimulation of the superior sagittal sinus (SSS) in the cat....... In eleven anaesthetized cats external jugular vein blood samples were analyzed by radioimmunoassay for CGRP levels in three settings: a) control, b) 1 min after SSS stimulation and c) 1 min after SSS stimulation in presence of drug. Stimulation of the SSS resulted in release of CGRP from the external...

  18. Endocrine cells producing regulatory peptides.

    Science.gov (United States)

    Solcia, E; Usellini, L; Buffa, R; Rindi, G; Villani, L; Zampatti, C; Silini, E

    1987-07-15

    Recent data on the immunolocalization of regulatory peptides and related propeptide sequences in endocrine cells and tumors of the gastrointestinal tract, pancreas, lung, thyroid, pituitary (ACTH and opioids), adrenals and paraganglia have been revised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory polypeptide), neurotensin, glicentin/glucagon-37 and PYY (peptide tyrosine tyrosine) are the main products of gastrointestinal endocrine cells; glucagon, CRF (corticotropin releasing factor), somatostatin, PP (pancreatic polypeptide) and GRF (growth hormone releasing factor), in addition to insulin, are produced in pancreatic islet cells; bombesin-related peptides are the main markers of pulmonary endocrine cells; calcitonin and CGRP (calcitonin gene-related peptide) occur in thyroid and extrathyroid C cells; ACTH and endorphins in anterior and intermediate lobe pituitary cells, alpha-MSH and CLIP (corticotropin-like intermediate lobe peptide) in intermediate lobe cells; met- and leu-enkephalins and related peptides in adrenal medullary and paraganglionic cells as well as in some gut (enterochromaffin) cells; NPY (neuropeptide Y) in adrenaline-type adrenal medullary cells, etc.. Both tissue-appropriate and tissue-inappropriate regulatory peptides are produced by endocrine tumours, with inappropriate peptides mostly produced by malignant tumours.

  19. 沙鼠脑缺血再灌注损伤后细胞间黏附分子1及降钙素基因相关肽变化与阿司匹林的干预效应%Effect of aspirin on the expressions of intercellular adhesion molecule 1 and calcitonin-gene-related peptide in gerbils with ischemic reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    刘爽; 李义召; 张涛

    2006-01-01

    .05];而阿司匹林干预组细胞间黏附分子表达水平,在所有时限均明显低于缺血再灌注组,差异有显著性意义[分别为(0.96±0.83)%,(2.76±2.10)%,(1.96±1.09)%,P<0.05].②降钙素基因相关肽表达的变化:在脑缺血再灌注后24 h,3,7 d缺血再灌注组动物降钙素基因相关肽都呈弱阳性表达[分别为(3.12±2.26)%,(2.68±2.04)%,(2.57±1.97)%];而阿司匹林干预组则呈强阳性表达[分别为(4.98±2.47)%,(5.97±2.35)%,(6.04±2.40)%].结论:脑缺血再灌注可诱导细胞间黏附分子1表达上调,并抑制降钙素基因相关肽的表达;阿司匹林通过抑制细胞间黏附分子1表达水平和增强降钙素基因相关肽表达,从而达到较好的脑保护作用.%BACKGROUND: With the development of thrombolysis therapy in recent years, there has been an increasing focus on the protective effect of ischemic reperfusion injury (IRI) and its mechanism at home and abroad,and aspirin is of great importance in the treatment of thrombus diseases owing to its powerful antiplatelet aggregative activity.OBJECTIVE: To explore the protective effect of aspirin on the gerbil brains with IRI and its influence on the intercellular adhesion molecule (ICAM) and calcitonin gene-related peptide (CGRP) expressions.DESIGN: A randomized controlled animal experiments.SETTING: Department of Neurology, Jinan Municipal Central Hospital,College of Clinical Medicine, Shandong University.MATERIALS: The experiment was performed at the Physiological Laboratory of Taishan Medical University from December 2001 to June 2002.Sixty-three healthy male gerbils of Mongolian specimen were randomly assigned into sham group, IRI group and aspirin group with 21 in each group. And each group was further divided into three subgroups according to the time after IRI: 24 hours, 3 days and 7 days, with 7 gerbils for each.METHODS: The models of global brain IRI were established by bilateral carotid artery occlusion. Sham group: The unfolded bilateral

  20. 慢性肾功能衰竭患者血液透析前后血管活性因子的变化及临床意义%The changes and significance of the plasma levels of nitric oxide,endothelin,atrial natriuretic peptide and angiotensinⅡ in chronic renal failure patients receiving hemodialysis therapy

    Institute of Scientific and Technical Information of China (English)

    黄桂芬; 崔志强; 孙亦兵

    2001-01-01

    Objective:To investigate the changes and clinical significance of plasma levels of nitric oxide (NO),endothelin(ET),atrial natriuretic peptide(ANP),plasma renin activity(PRA) and angiotensinⅡ(ATⅡ) before and after hemodialysis in patients with chronic renal failure(CRF).Methods:Sixty patients with CRF(30 patients with uncompensated chronic renal dysfunction and the other 30 patients with chronic renal failure) were included in the study.Thirty healthy volunteer were chosen as normal control.Blood samples were collected before and after hemodialysis.The plasma NO was assayed using colorimetry and the plasma ET,ANP,PRA and ATⅡ were determined by radioimmunoassay.Results:The plasma levels of NO,ET,ANP,PRA and ATⅡ in the group of CRF were significant higher than those of control (P0.05)。结论:血液透析可使CRF患者血浆NO、ANP降低,PRA、ATⅡ升高,提示ET升高可增加ANP和PRA水平,ANP浓度可抑制ATⅡ的分泌。

  1. Circulating levels of vasoactive peptides in patients with acute bacterial meningitis

    DEFF Research Database (Denmark)

    Berg, Ronan Martin Griffen; Strauss, Gitte Irene; Tofteng, Flemming

    2009-01-01

    PURPOSE: The underlying mechanisms for cerebral blood flow (CBF) abnormalities in acute bacterial meningitis (ABM) are largely unknown. Putative mediators include vasoactive peptides, e.g. calcitonin-gene related peptide (CGRP), vasoactive intestinal peptide (VIP), and endothelin-1 (ET-1), all of...

  2. Gastroprotective mechanisms of Citrus lemon (Rutaceae) essential oil and its majority compounds limonene and β-pinene: involvement of heat-shock protein-70, vasoactive intestinal peptide, glutathione, sulfhydryl compounds, nitric oxide and prostaglandin E₂.

    Science.gov (United States)

    Rozza, Ariane Leite; Moraes, Thiago de Mello; Kushima, Hélio; Tanimoto, Alexandre; Marques, Márcia Ortiz Mayo; Bauab, Taís Maria; Hiruma-Lima, Clélia Akiko; Pellizzon, Cláudia Helena

    2011-01-15

    Citrus lemon (CL) belongs to Rutaceae family and is popularly known in Brazil as limão siciliano. The phytochemical analysis of CL fruit bark essential oil showed two majority components, limonene (LIM) and β-pinene (PIN). This study aimed to evaluate the gastroprotective mechanism of action from CL, LIM and PIN in ethanol- and indomethacin-induced gastric ulcers and its in vitro anti-Helicobacter pylori activity. After ethanol-induced gastric ulcer, the ulcer area was measured and the stomachs were destined to histology (HE and PAS), immunohistochemistry for HSP-70 and VIP and glutathione (GSH) measurement. The involvement of nitric oxide (NO) and sulfhydryl (SH) compounds was determined. The ulcer area for indomethacin-induced gastric ulcers was measured. PGE₂ concentration was biochemically measured. The minimum inhibitory concentration (MIC) against H. pylori was determined in vitro. In ethanol model, CL and LIM demonstrated 100% of gastroprotection, while PIN did not exert effective gastroprotection (53.26%). In the indomethacin model, CL and LIM offered effective gastroprotection but PIN did not show gastroprotective effect. The gastric ulcer area of rats pretreated with NO-synthase inhibitor or SH-blocker was decreased in comparison to the control group. The MIC obtained for CL was 125 μg/mL, for LIM was 75 μg/mL and for PIN was 500 μg/mL. The gastroprotective effect of CL and LIM was involved with increasing in mucus secretion, HSP-70 and VIP, but not with GSH, NO or SH compounds. CL gastroprotective mechanism is involved with PGE₂. PIN did not present gastroprotective activity.

  3. Glucagon-like peptide-1 excites firing and increases GABAergic miniature postsynaptic currents (mPSCs in gonadotropin-releasing hormone (GnRH neurons of the male mice via activation of nitric oxide (NO and suppression of endocannabinoid signaling pathways

    Directory of Open Access Journals (Sweden)

    Imre Farkas

    2016-09-01

    Full Text Available Glucagon-like peptide-1 (GLP-1, a metabolic signal molecule, regulates reproduction, although, the involved molecular mechanisms have not been elucidated, yet. Therefore, responsiveness of gonadotropin-releasing hormone (GnRH neurons to the GLP-1 analog Exendin-4 and elucidation of molecular pathways acting downstream to the GLP-1 receptor (GLP-1R have been challenged. Loose patch-clamp recordings revealed that Exendin-4 (100 nM–5 μM elevated firing rate in hypothalamic GnRH-GFP neurons of male mice via activation of GLP-1R. Whole-cell patch-clamp measurements demonstrated increased excitatory GABAergic miniature postsynaptic currents (mPSCs frequency after Exendin-4 administration, which was eliminated by the GLP-1R antagonist Exendin-3(9-39 (1 μM. Intracellular application of the G-protein inhibitor GDP-beta-S (2 mM impeded action of Exendin-4 on mPSCs, suggesting direct excitatory action of GLP-1 on GnRH neurons. Blockade of nitric-oxide (NO synthesis by L-NAME (100 μM or NPLA (1 μM or intracellular scavenging of NO by CPTIO (1 mM partially attenuated the excitatory effect of Exendin-4. Similar partial inhibition was achieved by hindering endocannabinoid pathway using CB1 inverse-agonist AM251 (1 μM. Simultaneous blockade of NO and endocannabinoid signaling mechanisms eliminated action of Exendin-4 suggesting involvement of both retrograde machineries. Intracellular application of the TRPV1-antagonist AMG9810 (10 μM or the FAAH-inhibitor PF3845 (5 μM impeded the GLP-1-triggered endocannabinoid pathway indicating an anandamide-TRPV1-sensitive control of 2-AG production. Furthermore, GLP-1 immunoreactive axons innervated GnRH neurons in the hypothalamus suggesting that GLP-1 of both peripheral and neuronal sources can modulate GnRH neurons. RT-qPCR study confirmed the expression of GLP-1R and nNOS mRNAs in GnRH-GFP neurons. Immuno-electron microscopic analysis revealed the presence of neuronal nitric oxide synthase (nNOS protein in Gn

  4. Influence of C-Peptide on Glucose Utilisation

    Directory of Open Access Journals (Sweden)

    B. Wilhelm

    2008-01-01

    Full Text Available During the recent years, multiple studies demonstrated that C-peptide is not an inert peptide, but exerts important physiological effects. C-peptide binds to cell membranes, stimulates the Na,K-ATPase and the endothelial nitric oxide (NO synthase. Moreover, there is evidence that C-peptide decreases glomerular hyperfiltration and increases glucose utilisation. Nevertheless, there is still limited knowledge concerning mechanisms leading to an increased glucose utilisation either in rats or in humans. The aim of this paper is to give an overview over the published studies regarding C-peptide and glucose metabolism from in vitro studies to longer lasting studies in humans.

  5. β-淀粉样蛋白对小胶质细胞合成一氧化氮的影响%Effect of amyloid beta-peptide on activated microglial cell excreting nitric oxide

    Institute of Scientific and Technical Information of China (English)

    韩笑峰; 吕丽; 葛汝丽; 唐荣华

    2008-01-01

    目的 探讨β-淀粉样蛋白(arnyloid beta-peptide,AB)诱导小胶质细胞活化后K轻链核因子(nuclear factor-kappa B,NF-kB)的表达及一氧化氮(NO)水平的变化.方法 Ap干预纯化培养的小胶质细胞,观察其形态学变化,采用镉还原法测定NO水平,免疫细胞化学方法研究NF-KB的表达.结果 500 nmol/L及1000 mnol/L AB干预组细胞形态呈"阿米巴样",细胞核内NF-kB的表达增加(P<0.05),培养基中NO浓度升高(P<0.05).结论 AB激活小胶质细胞NF-kB途径大量合成NO,可能参与阿尔茨海默病(Alzheimer's disease,AD)的致病过程.

  6. INHIBITORY EFFECTS OF NITRIC OXIDE AND ATRIAL NATRI- URETIC PEPTIDE ON THE INCREASE IN RENAL AFFERENT NERVE ACTIVITY INDUCED BY INTR ARENAL ARTERIAL INJECTION OF ET-1 IN ANESTHETIZED RATS%NO和ANP对内皮素引起大鼠肾神经 传入放电增加的阻抑作用

    Institute of Scientific and Technical Information of China (English)

    夏晓红; 何瑞荣

    2001-01-01

    目的和方法:采用电生理学技术观察一氧化氮(NO)和心房钠尿肽(A NP)对肾动脉内注射内皮索(ET)所致麻醉大鼠肾神经传入放电(RANA)的影响。结 果:①肾动脉内注射ET-1后平均动脉压(MAP)先有短暂的降低随后为较显著的持 久增高,RANA明显增加;②肾动脉内分别注射NO前体L-Arg和ANP后,ET-1的上述效应 即被阻抑。结论:肾动脉内注射ET-1引起RANA明显增加,而此效应可 被同一途径注射NO和ANP所消除。%By using electrophysiological technique, the effects of nitric oxide (NO) and atrial natriuretic peptide (ANP) on renal afferent nerve activity (RANA) induced by intrarenal arterial injection of endothelin-1(ET-1) were examined in anesthetized rat. Results: (1) In response to intrarenal arterial injection of ET-1 (1μg/kg)MAP was initially decreased and subsequently increased, and RANA was increased to 208.33±16.60%(P<0.001). ( 2)Pretreatment with L-Arg or ANP could effectively inhibit the above biological actions induced by ET-1. Conclusion: Intrarenal arterial in jection of ET-1 can markedly induce the increase in RANA, an effect which is ab olishd by L-arg or ANP administered by the same route.

  7. Effect of antibacterial peptide FALL-39 and its mutant peptides on production of nitric oxide induced by lipopolysaccharides%抗菌肽FALL-39及其突变肽对诱生型一氧化氮产生的影响

    Institute of Scientific and Technical Information of China (English)

    郝杰; 杨云霞; 王伯瑶

    2008-01-01

    目的:比较人抗茵肤FALL-39及其突变肽对细菌脂多糖(lipopolysaccharides,LPS)介导的诱生型一氧化氮(nitric oxide.NO)产生的影响.方法:体外常规培养人单核吞噬细胞THP-1,LPS刺激细胞,分别用人抗茵肽FALL-39以及突变肽FALL-39-Lys24,FALL-39-Lys32,FALL-39-Lys24′32处理细胞.应用RT-PCR方法测定LPS诱生型一氧化氮合酶(induced nitric oxide synthase,iNOS)以及FALL-39 mRNA的表达,用硝酸还原酶法测定细胞培养上清液中NO的含量.小鼠腹腔注射更生霉素和LPS建立内毒素血症模型,分别用抗茵肽处理动物,取血测定血清中NO的含量.结果:LPS刺激FALL-39 mRNA的表达增加; 同时也诱导NO mRNA的表达以及细胞培养上清液中NO含量的增加.人抗菌肤FALL-39及其突变肽FALL-39-Lye24,FALL-39-Lys32,FALL-39-Lys24′32可以抑制LPS诱导的NO的产生; 其中FALL-39-Lys24′32的抑制作用最为明显.结论:抗茵肽FALL-39及其突变肽具有抗内毒素作用,其机制与抑制LPS诱导的NO产生有关.

  8. 一氧化氮、血管活性肠肽与压力性尿失禁关系的实验研究%The experimental study of the relationship between the nitric oxide, vasoactive intestinal peptide and stress urinary incontinence

    Institute of Scientific and Technical Information of China (English)

    杨海北; 方克伟; 李泽惠; 钱忠义

    2011-01-01

    目的 明确压力性尿失禁(SUI)模型SD老鼠的尿道、阴道、肛提肌中非肾上腺素非胆碱能神经递质一氧化氮(NO)与血管活性肠肽(VIP)的分布规律及其表达差异,探讨NO与VIP在SUI发病机制中的作用.方法 从成功建模的Sprague-Dawley(SD)雌性大鼠中选择12只作为实验组,另外12只未经任何处理的正常大鼠作为对照组.处死所有实验对象,取尿道、阴道、肛提肌行HE染色及免疫组化染色(ABC法)检测上述组织内NO与VIP的分布规律及其表达差异,用积分光密度衡量,结果用独立样本t检验进行统计学分析.结果 (1)HE染色见对照组大鼠的尿道,阴道、肛提肌染色均匀,各种细胞体积大小正常,肌纤维排列整齐;实验组表现为组织染色不均匀,组织水肿,萎缩变薄,肌纤维排列疏松、稍紊乱,有少量炎症反应及细胞坏死.(2)免疫组化染色表明对照组大鼠尿道、阴道、肛提肌NO的积分光密度分别为:3.95±1.02、6.01±1.32、18.67±4.94.实验组则分别为:1.04±0.38、1.44±0.48、6.16±1.32;VIP的积分光密度在对照组大鼠尿道、阴道、肛提肌分别为:3.57±0.77、7.15±1.67、20.29±3.39.实验组则分别为:0.73±0.23、2.51±0.60、3.69±1.24.对照组和实验组大鼠尿道、阴道、肛提肌中NO与VIP的表达有显著差异,差异有统计学意义(p<0.01).结论 (1)盆底肌肉组织变性,水肿导致盆底支持力量减弱可能与SUI发生有关;(2)非肾上腺素非胆碱能神经递质NO和VIP在血管周围最多,主要在肌浆中表达;实验组与对照组的差异说明NO与VIP参与了SUI的发生、发展.%Objectives To determine both the distribution and expression of non-adrenergic and noncholinergic neurotransmitters(NANC) nitric oxide (NO) and vasoactive intestinal peptide (VIP) in the urethra, vagina, elevator ani muscle of the SUI model rats. And to clarify their roles in the pathogenesis of SUI. Methods Choosing 12 SUI SD rats as experimental

  9. Nitric oxide-releasing aspirin but not conventional aspirin improves healing of experimental colitis

    Institute of Scientific and Technical Information of China (English)

    Malgorzata Zwolinska-Wcislo; Tomasz Brzozowski; Agata Ptak-Belowska; Aneta Targosz; Katarzyna Urbanczyk; Slawomir Kwiecien; Zbigniew Sliwowski

    2011-01-01

    -treatment with calcitonin gene related peptide (CGRP) and NO-ASA in capsaicin-denervated animals. CONCLUSION: NO-releasing ASA, in contrast to ASA, COX-1 inhibitors, and SC-560, accelerated the healing of colitis via a mechanism involving NO mediated improvement of microcirculation and activation of sensory nerves releasing CGRP.

  10. Bioactive Peptides

    Directory of Open Access Journals (Sweden)

    Eric Banan-Mwine Daliri

    2017-04-01

    Full Text Available The increased consumer awareness of the health promoting effects of functional foods and nutraceuticals is the driving force of the functional food and nutraceutical market. Bioactive peptides are known for their high tissue affinity, specificity and efficiency in promoting health. For this reason, the search for food-derived bioactive peptides has increased exponentially. Over the years, many potential bioactive peptides from food have been documented; yet, obstacles such as the need to establish optimal conditions for industrial scale production and the absence of well-designed clinical trials to provide robust evidence for proving health claims continue to exist. Other important factors such as the possibility of allergenicity, cytotoxicity and the stability of the peptides during gastrointestinal digestion would need to be addressed. This review discusses our current knowledge on the health effects of food-derived bioactive peptides, their processing methods and challenges in their development.

  11. Bioactive Peptides.

    Science.gov (United States)

    Daliri, Eric Banan-Mwine; Oh, Deog H; Lee, Byong H

    2017-04-26

    The increased consumer awareness of the health promoting effects of functional foods and nutraceuticals is the driving force of the functional food and nutraceutical market. Bioactive peptides are known for their high tissue affinity, specificity and efficiency in promoting health. For this reason, the search for food-derived bioactive peptides has increased exponentially. Over the years, many potential bioactive peptides from food have been documented; yet, obstacles such as the need to establish optimal conditions for industrial scale production and the absence of well-designed clinical trials to provide robust evidence for proving health claims continue to exist. Other important factors such as the possibility of allergenicity, cytotoxicity and the stability of the peptides during gastrointestinal digestion would need to be addressed. This review discusses our current knowledge on the health effects of food-derived bioactive peptides, their processing methods and challenges in their development.

  12. Nitric oxide and cardiovascular system.

    Science.gov (United States)

    Cengel, Atiye; Sahinarslan, Asife

    2006-12-01

    Endothelium has many important functions including the control of blood-tissue permeability and vascular tonus, regulation of vascular surface properties for homeostasis and inflammation. Nitric oxide is the chief molecule in regulation of endothelial functions. Nitric oxide deficiency, which is also known as endothelial dysfunction, is the first step for the occurrence of many disease states in cardiovascular system including heart failure, hypertension, dyslipidemia, insulin resistance, diabetes mellitus, hyperhomocysteinemia and smoking. This review deals with the importance of nitric oxide for cardiovascular system. It also includes the latest improvements in the diagnosis and treatment of endothelial dysfunction.

  13. 49 CFR 173.158 - Nitric acid.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Nitric acid. 173.158 Section 173.158... Nitric acid. (a) Nitric acid exceeding 40 percent concentration may not be packaged with any other material. (b) Nitric acid in any concentration which does not contain sulfuric acid or hydrochloric acid as...

  14. 49 CFR 173.337 - Nitric oxide.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Nitric oxide. 173.337 Section 173.337... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.337 Nitric oxide. (a) Nitric oxide must be... valve and valve seat that will not deteriorate in contact with nitric oxide. Cylinders or valves may...

  15. Differential expression of genes related to gain and intake in the liver of beef cattle

    Science.gov (United States)

    Background: To better understand which genes play a role in cattle feed intake and gain, we evaluated differential expression of genes related to gain and intake in the liver of crossbred beef steers. Based on past transcriptomics studies on cattle liver, we hypothesized that genes related to metabo...

  16. Peptide identification

    Science.gov (United States)

    Jarman, Kristin H [Richland, WA; Cannon, William R [Richland, WA; Jarman, Kenneth D [Richland, WA; Heredia-Langner, Alejandro [Richland, WA

    2011-07-12

    Peptides are identified from a list of candidates using collision-induced dissociation tandem mass spectrometry data. A probabilistic model for the occurrence of spectral peaks corresponding to frequently observed partial peptide fragment ions is applied. As part of the identification procedure, a probability score is produced that indicates the likelihood of any given candidate being the correct match. The statistical significance of the score is known without necessarily having reference to the actual identity of the peptide. In one form of the invention, a genetic algorithm is applied to candidate peptides using an objective function that takes into account the number of shifted peaks appearing in the candidate spectrum relative to the test spectrum.

  17. Distribution, chemical coding and origin of nitric oxide synthase-containing nerve fibres in the guinea pig nasal mucosa.

    Science.gov (United States)

    Kondo, T; Inokuchi, T; Ohta, K; Annoh, H; Chang, J

    2000-04-12

    The distribution, chemical coding and origin of nitric oxide synthase (NOS)-containing nerve fibres in the respiratory mucosa of the nasal septum of the guinea pig were examined using nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry and immunohistochemistry. A rich supply of NADPH-d-positive nerve fibres was observed around blood vessels and in nasal glands where nerve fibres frequently penetrated into the epithelia of acini and intralobular ducts. NADPH-d reactivity was also found in the nerve fibres located under or within the respiratory epithelium. Combined immunofluorescence and histochemical staining of the same preparation demonstrated virtually complete overlapping of NOS immunoreactivity and NADPH-d reactivity in nerve fibres, indicating that NADPH-d can be used as a marker for NOS-containing neurons. Double-labelling using antibodies to vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP) revealed that NADPH-d-positive nerve fibres frequently contained VIP or NPY, but not CGRP. Pterygopalatine ganglionectomy significantly reduced the number of NADPH-d-positive nerve fibres innervating the respiratory epithelium as well as blood vessels and nasal glands. Neither superior cervical ganglionectomy nor sensory denervation by capsaicin treatment affected the distribution of NADPH-d-positive fibres. These results indicate that NOS-containing nerve fibres innervating the respiratory epithelium as well as blood vessels and nasal glands in the guinea pig originate mainly from the pterygopalatine ganglion, and suggest that NO may play a significant role as a neurotransmitter and/or neuromodulator in the control of the respiratory epithelium as well as vasculature and nasal glands.

  18. Transcriptomic Response to Nitric Oxide Treatment in Larix olgensis Henry

    Directory of Open Access Journals (Sweden)

    Xiaoqing Hu

    2015-12-01

    Full Text Available Larix olgensis Henry is an important coniferous species found in plantation forests in northeastern China, but it is vulnerable to pathogens. Nitric oxide (NO is an important molecule involved in plant resistance to pathogens. To study the regulatory role of NO at the transcriptional level, we characterized the transcriptomic response of L. olgensis seedlings to sodium nitroprusside (SNP, NO donor using Illumina sequencing and de novo transcriptome assembly. A significant number of putative metabolic pathways and functions associated with the unique sequences were identified. Genes related to plant pathogen infection (FLS2, WRKY33, MAPKKK, and PR1 were upregulated with SNP treatment. This report describes the potential contribution of NO to disease resistance in L. olgensis as induced by biotic stress. Our results provide a substantial contribution to the genomic and transcriptomic resources for L. olgensis, as well as expanding our understanding of the involvement of NO in defense responses at the transcriptional level.

  19. Transcriptomic Response to Nitric Oxide Treatment in Larix olgensis Henry.

    Science.gov (United States)

    Hu, Xiaoqing; Yang, Jingli; Li, Chenghao

    2015-12-02

    Larix olgensis Henry is an important coniferous species found in plantation forests in northeastern China, but it is vulnerable to pathogens. Nitric oxide (NO) is an important molecule involved in plant resistance to pathogens. To study the regulatory role of NO at the transcriptional level, we characterized the transcriptomic response of L. olgensis seedlings to sodium nitroprusside (SNP, NO donor) using Illumina sequencing and de novo transcriptome assembly. A significant number of putative metabolic pathways and functions associated with the unique sequences were identified. Genes related to plant pathogen infection (FLS2, WRKY33, MAPKKK, and PR1) were upregulated with SNP treatment. This report describes the potential contribution of NO to disease resistance in L. olgensis as induced by biotic stress. Our results provide a substantial contribution to the genomic and transcriptomic resources for L. olgensis, as well as expanding our understanding of the involvement of NO in defense responses at the transcriptional level.

  20. Differential distribution of calcitonin gene-related peptide and its receptor components in the human trigeminal ganglion

    DEFF Research Database (Denmark)

    Eftekhari, S; Salvatore, C A; Calamari, A;

    2010-01-01

    system and hence the potential antagonist sites of action remain unknown. Therefore we designed a study to evaluate the localization of CGRP and its receptor components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein (RAMP) 1 in the human trigeminal ganglion using...... immunohistochemistry and compare with that of rat. Antibodies against purified CLR and RAMP1 proteins were produced and characterized for this study. Trigeminal ganglia were obtained at autopsy from adult subjects and sections from rat trigeminal ganglia were used to compare the immunostaining pattern. The number...

  1. The Experimental Study on the Effect Calcitonin Gene-related Peptide on Bone Resorption Mediated by Interleukin-1

    Institute of Scientific and Technical Information of China (English)

    LIAN; Kai(

    2001-01-01

    [1]Suda T Udagawa I Nakamura T et al.Modulation of osteoclast? Differentiation by local factors.Bone 1995 17(suppl 2) :875[2]Kanehisa J Heersche J N M.Osteoclastic bone resorption:in vitro analysis of the rate of resorption and migration of individual osteoclasts.Bone 1988 9:73[3]高建军.破骨细胞成熟和活化以及骨吸收机制.内分泌学分册 1998 18(2):57[4]Cohen-Solal M E Granlet A M Denne M A et al.Peripheral blood monocyte culture supernatants of menopausel women can induce bone resorption:involvement of cytokines.J Clin Endocrinol Metab 1993 77:1648[5]Kimble R B Vannice J L Bloedow D C et al.Interleukin-1 receptor antagonist decreases bone loss and bone resorption in ovariectomized rats.J Clin Invest 1994 93:1959[6]Horowitz M C.Cytokines and estrogen in bone:Antiosteoporotic ettects.Science 1993 260:626[7]Thomson B M Saklatvala J Chambers T J et al.Osteoblasts mediate interleukin 1 stimulation of bone resorption by rat osteoclasts.J Exp Med 1986 164:104[8]Goltzman D Mitchell J.Interaction of calciton and CGRP at receptor sites in target tissue.Science 1985 227:1343[9]Millet I Vignery A.The neuropeptide CGRP inhibits TNF-α but poorly induces IL-6 production by fetal rat osteoblasts.Cytokine 1997 12(9):999[10]Taichman R S Hauschka P V.Effects of IL-1βand TNF-α on osteoblastic expression of osteocalcin and mineralized extracellular matrix in vitro.Inflammation.1992 16:587

  2. The role of calcium in endotoxin-induced release of calcitonin gene-related peptide (CGRP) from rat spinal cord

    Institute of Scientific and Technical Information of China (English)

    唐跃明; 韩启德; 王宪

    1997-01-01

    In the present study, the role of calcium in endotoxin-induced CGRP release was studied. 2 .5-50 μg/mL endotoxin and 1 -10 mmol/L caffeine caused concentration-dependent increase of CGRP release from rat spinal cord in vitro. However, no additive effect could he found when caffeine and endotoxin were concomitantly incubated. By using capsaicin, Ca2+-free medium, Omega-Conotoxin, nifedipine, W-7, ryanodine, MgCl2, Tris-ATP, rutheni-um red, the results indicate that the release of CGRP evoked by endotoxin from the sensory fibers of rat spinal cord is dependent on extracellular calcium. After entering into the cell through the N-type calcium channel, calcium binds to calmodulin, and triggers calcium release from intracellular calcium store by activating the caffeine-sensitive but ryan-odine-insensitive mechanism.

  3. Sumatriptan does not change calcitonin gene-related peptide in the cephalic and extracephalic circulation in healthy volunteers

    DEFF Research Database (Denmark)

    Hansen, Jakob Møller; Petersen, Jesper; Wienecke, Troels;

    2009-01-01

    not differ between the four vascular compartments (P=0.49). It was found that Sumatriptan did not change the levels of circulating CGRP in the intra or extracerebral circulation in healthy volunteers. This speaks against a direct CGRP-reducing effect of sumatriptan in vivo in humans when the trigemino...

  4. Calcitonin gene-related peptide in medullary thyroid carcinomas: characterization of molecular forms including the amidated C-terminus.

    Science.gov (United States)

    Schifter, S; Johnsen, A H

    1994-01-01

    CGRP was extracted from three familial and four sporadic medullary thyroid carcinomas (MTC) and was measured by an assay specific for the amidated C-terminus. The antibody showed equal affinity for alpha- and beta-CGRP. All tumors contained high concentrations of CGRP (range: 63-7889 pmol/g) compared to spinal cord (86 pmol/g), thyroid gland (4 pmol/g), and two small-cell lung carcinomas (4 and 1 pmol/g, respectively). The concentration of calcitonin (CT) was determined with an assay specific for an epitope involving the midportion and C-terminal end of the molecule. In six of the seven tumors investigated, concentrations of CT were found to be higher than for CGRP. Gel chromatography showed heterogeneity with respect to CGRP immunoreactivity. Thus, in all seven extracts, three peaks were seen with Kd values 0.37, 0.63, and 0.80, respectively. This profile of immunoreactive CGRP was similar to that obtained from human medulla spinalis, thereby indicating normal posttranslational processing of pro-CGRP in MTC tumors. Further characterization of the three main peaks identified by gel chromatography was performed on pooled fractions from one of the tumors using HPLC, sequencing, and mass spectrometry. The immunoreactive peak with Kd 0.37 was identified as human beta-CGRP, the peak with Kd 0.63 as 19-37 beta-CGRP, and the peak with Kd 0.80 as 25-37 beta-CGRP. No alpha-CGRP was identified in this tumor. This indicates selective expression of beta-CGRP, at least in the tumor investigated.

  5. Localisation and neural control of the release of calcitonin gene-related peptide (CGRP) from the isolated perfused porcine ileum

    DEFF Research Database (Denmark)

    Rasmussen, T N; Schmidt, P; Poulsen, S S

    2001-01-01

    extracts, CGRP-LI corresponded entirely to porcine CGRP plus smaller amounts of oxidised CGRP. Using isolated vascularly perfused segments of the ileum, we studied the release of CGRP-LI in response to electrical stimulation of the mixed extrinsic periarterial nerves and to infusion of different...... neuroblockers. In addition, the effect of infusion of capsaicin was studied. The basal output of CGRP-LI was 2.9+/-0.7 pmol/5 min (mean+/-S.D.). Electrical nerve stimulation (8 Hz) significantly increased the release of CGRP-LI to 167+/-16% (mean+/-S.E.M.) of the basal output (n=13). This response...

  6. Glucagon-Like Peptide-1 Excites Firing and Increases GABAergic Miniature Postsynaptic Currents (mPSCs) in Gonadotropin-Releasing Hormone (GnRH) Neurons of the Male Mice via Activation of Nitric Oxide (NO) and Suppression of Endocannabinoid Signaling Pathways

    Science.gov (United States)

    Farkas, Imre; Vastagh, Csaba; Farkas, Erzsébet; Bálint, Flóra; Skrapits, Katalin; Hrabovszky, Erik; Fekete, Csaba; Liposits, Zsolt

    2016-01-01

    Glucagon-like peptide-1 (GLP-1), a metabolic signal molecule, regulates reproduction, although, the involved molecular mechanisms have not been elucidated, yet. Therefore, responsiveness of gonadotropin-releasing hormone (GnRH) neurons to the GLP-1 analog Exendin-4 and elucidation of molecular pathways acting downstream to the GLP-1 receptor (GLP-1R) have been challenged. Loose patch-clamp recordings revealed that Exendin-4 (100 nM–5 μM) elevated firing rate in hypothalamic GnRH-GFP neurons of male mice via activation of GLP-1R. Whole-cell patch-clamp measurements demonstrated increased excitatory GABAergic miniature postsynaptic currents (mPSCs) frequency after Exendin-4 administration, which was eliminated by the GLP-1R antagonist Exendin-3(9–39) (1 μM). Intracellular application of the G-protein inhibitor GDP-β-S (2 mM) impeded action of Exendin-4 on mPSCs, suggesting direct excitatory action of GLP-1 on GnRH neurons. Blockade of nitric-oxide (NO) synthesis by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME; 100 μM) or N5-[Imino(propylamino)methyl]-L-ornithine hydrochloride (NPLA; 1 μM) or intracellular scavenging of NO by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO; 1 mM) partially attenuated the excitatory effect of Exendin-4. Similar partial inhibition was achieved by hindering endocannabinoid pathway using cannabinoid receptor type-1 (CB1) inverse-agonist 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-(1-piperidyl) pyrazole-3-carboxamide (AM251; 1 μM). Simultaneous blockade of NO and endocannabinoid signaling mechanisms eliminated action of Exendin-4 suggesting involvement of both retrograde machineries. Intracellular application of the transient receptor potential vanilloid 1 (TRPV1)-antagonist 2E-N-(2, 3-Dihydro-1,4-benzodioxin-6-yl)-3-[4-(1, 1-dimethylethyl)phenyl]-2-Propenamide (AMG9810; 10 μM) or the fatty acid amide hydrolase (FAAH)-inhibitor PF3845 (5 μM) impeded the GLP-1-triggered endocannabinoid

  7. C-Peptide Test

    Science.gov (United States)

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities C-peptide Share this page: Was this page helpful? Also known as: Insulin C-peptide; Connecting Peptide Insulin; Proinsulin C-peptide Formal ...

  8. De novo sequencing of two novel peptides homologous to calcitonin-like peptides, from skin secretion of the Chinese Frog, Odorrana schmackeri

    Directory of Open Access Journals (Sweden)

    Geisa P.C. Evaristo

    2015-09-01

    Full Text Available An MS/MS based analytical strategy was followed to solve the complete sequence of two new peptides from frog (Odorrana schmackeri skin secretion. This involved reduction and alkylation with two different alkylating agents followed by high resolution tandem mass spectrometry. De novo sequencing was achieved by complementary CID and ETD fragmentations of full-length peptides and of selected tryptic fragments. Heavy and light isotope dimethyl labeling assisted with annotation of sequence ion series. The identified primary structures are GCD[I/L]STCATHN[I/L]VNE[I/L]NKFDKSKPSSGGVGPESP-NH2 and SCNLSTCATHNLVNELNKFDKSKPSSGGVGPESF-NH2, i.e. two carboxyamidated 34 residue peptides with an aminoterminal intramolecular ring structure formed by a disulfide bridge between Cys2 and Cys7. Edman degradation analysis of the second peptide positively confirmed the exact sequence, resolving I/L discriminations. Both peptide sequences are novel and share homology with calcitonin, calcitonin gene related peptide (CGRP and adrenomedullin from other vertebrates. Detailed sequence analysis as well as the 34 residue length of both O. schmackeri peptides, suggest they do not fully qualify as either calcitonins (32 residues or CGRPs (37 amino acids and may justify their classification in a novel peptide family within the calcitonin gene related peptide superfamily. Smooth muscle contractility assays with synthetic replicas of the S–S linked peptides on rat tail artery, uterus, bladder and ileum did not reveal myotropic activity.

  9. Endothelial nitric oxide: protector of a healthy mind.

    Science.gov (United States)

    Katusic, Zvonimir S; Austin, Susan A

    2014-04-01

    Endothelial nitric oxide (NO) is generated by constitutively active endothelial nitric oxide synthase (eNOS), an essential enzyme responsible for cardiovascular homeostasis. Historically, endothelial NO was first recognized as a major vasodilator involved in control of vasomotor function and local blood flow. In this review, our attention is focused on the emerging role of endothelial NO in linking cerebrovascular function with cognition. We will discuss the recognized ability of endothelial NO to modulate processing of amyloid precursor protein (APP), influence functional status of microglia, and affect cognitive function. Existing evidence suggests that the loss of NO in cultured human cerebrovascular endothelium causes increased expression of APP and β-site APP-cleaving enzyme 1 (BACE1) thereby resulting in increased secretion of amyloid β peptides (Aβ1-40 and Aβ1-42). Furthermore, increased expression of APP and BACE1 as well as increased production of Aβ peptides was detected in the cerebral microvasculature and brain tissue of eNOS-deficient mice. Since Aβ peptides are considered major cytotoxic molecules responsible for the pathogenesis of Alzheimer's disease, these observations support the concept that a loss of endothelial NO might significantly contribute to the initiation and progression of cognitive decline. In addition, genetic inactivation of eNOS causes activation of microglia and promotes a pro-inflammatory phenotype in the brain. Behavioural analysis revealed that eNOS-deficient mice exhibit impaired cognitive performance thereby indicating that selective loss of endothelial NO has a detrimental effect on the function of neuronal cells. Together with findings from prior studies demonstrating the ability of endothelial NO to affect synaptic plasticity, mitochondrial biogenesis, and function of neuronal progenitor cells, it is becoming apparent that the role of endothelial NO in the control of central nervous system function is very complex. We

  10. Peptide arrays for screening cancer specific peptides.

    Science.gov (United States)

    Ahmed, Sahar; Mathews, Anu Stella; Byeon, Nara; Lavasanifar, Afsaneh; Kaur, Kamaljit

    2010-09-15

    In this paper, we describe a novel method to screen peptides for specific recognition by cancer cells. Seventy peptides were synthesized on a cellulose membrane in an array format, and a direct method to study the peptide-whole cell interaction was developed. The relative binding affinity of the cells for different peptides with respect to a lead 12-mer p160 peptide, identified by phage display, was evaluated using the CyQUANT fluorescence of the bound cells. Screening allowed identification of at least five new peptides that displayed higher affinity (up to 3-fold) for MDA-MB-435 and MCF-7 human cancer cells compared to the p160 peptide. These peptides showed very little binding to the control (noncancerous) human umbilical vein endothelial cells (HUVECs). Three of these peptides were synthesized separately and labeled with fluorescein isothiocyanate (FITC) to study their uptake and interaction with the cancer and control cells using confocal laser scanning microscopy and flow cytometry. The results confirmed the high and specific affinity of an 11-mer peptide 11 (RGDPAYQGRFL) and a 10-mer peptide 18 (WXEAAYQRFL) for the cancer cells versus HUVECs. Peptide 11 binds different receptors on target cancer cells as its sequence contains multiple recognition motifs, whereas peptide 18 binds mainly to the putative p160 receptor. The peptide array-whole cell binding assay reported here is a complementary method to phage display for further screening and optimization of cancer targeting peptides for cancer therapy and diagnosis.

  11. Alternative to Nitric Acid Passivation

    Science.gov (United States)

    Kessel, Kurt R.

    2016-01-01

    Corrosion is an extensive problem that affects the National Aeronautics and Space Administration (NASA) and European Space Agency (ESA). The deleterious effects of corrosion result in steep costs, asset downtime affecting mission readiness, and safety risks to personnel. It is vital to reduce corrosion costs and risks in a sustainable manner. The primary objective of this effort is to qualify citric acid as an environmentally-preferable alternative to nitric acid for passivation of stainless steel alloys.

  12. Amplification of a Gene Related to Mammalian mdr Genes in Drug-Resistant Plasmodium falciparum

    Science.gov (United States)

    Wilson, Craig M.; Serrano, Adelfa E.; Wasley, Annemarie; Bogenschutz, Michael P.; Shankar, Anuraj H.; Wirth, Dyann F.

    1989-06-01

    The malaria parasite Plasmodium falciparum contains at least two genes related to the mammalian multiple drug resistance genes, and at least one of the P. falciparum genes is expressed at a higher level and is present in higher copy number in a strain that is resistant to multiple drugs than in a strain that is sensitive to the drugs.

  13. Óxido nítrico e peptídeo atrial natriurético na predição de complicações da gestação Nitric oxide and atrial natriuretic peptide in the prediction of pregnancy complications

    Directory of Open Access Journals (Sweden)

    Fabrício da Silva Costa

    2007-01-01

    Full Text Available OBJETIVO: verificar a acurácia das dosagens séricas maternas do peptídeo atrial natriurético (ANP e óxido nítrico (NO para predição de complicações da gravidez. MÉTODOS: a casuística compreendeu 49 mulheres primigestas. As gestantes foram incluídas no estudo na 18ªsemana, momento em que foi coletada a amostra sangüínea para a realização das dosagens séricas. O ANP foi dosado pelo método de radioimunoensaio, utilizando kits Euro-dianostica (2000, considerando anormais valores superiores a 237,4 pg/mL (percentil 95. A dosagem do NO foi realizada pelo método de quimiluminescência, sendo considerados como anormais valores superiores a 17,8 µmol/L (percentil 95. Para análise estatística, utilizaram-se o teste t não pareado para a análise das variáveis quantitativas contínuas de distribuição normal; o teste de Mann-Whitney para amostras quantitativas não-paramétricas; o teste exato de Fisher na avaliação dos parâmentros qualitativos; e o teste de Pearson na avaliação das correlações. RESULTADOS: os dados não mostraram diferença significativa na concentração sérica do ANP, considerando o grupo que apresentou complicações gestacionais e/ou perinatais (média de 139,3±77,1 pg/mL e o grupo controle (média de 119,6±47,0 pg/mlL, e nem na concentração sérica do NO, entre o grupo com complicações gestacionais e/ou perinatais (média de 11,1±4,6 µmol/L e o grupo controle (média de 10,0±3,4 µmol/L. CONCLUSÕES: os resultados mostram que o ANP e o NO não foram bons indicadores de complicações da gestação.PURPOSE: to verify the effectiveness of the maternal blood serum assays of the atrial natriuretic peptide (ANP and nitric oxide (NO to predict pregnancy complications. METHODS: the sample was made of 49 primigravidae women. They were included in the study at the 18th week of gestation, when blood sample was collected in order to analyze the serum assays. ANP was assayed by radioimmunoassay, using

  14. The Oxidation of Hydrazine by Nitric Acid

    Energy Technology Data Exchange (ETDEWEB)

    Karraker, D.G.

    2001-07-02

    Hydrazine nitrate-nitric acid solutions are used in the ion exchange process for separating Pu-238 and Np-237 and have been found to dissolve plutonium metal in a manner advantageous to SRP metal recovery operations. Laboratory tests on the stability of hydrazine in nitric acid solutions were performed to obtain accurate data, and the results of these tests are reported here. These tests provide sufficient information to specify temperature control for hydrazine-nitric acid solutions in plant processes.

  15. Genetic polymorphisms located in genes related to immune and inflammatory processes are associated with end-stage renal disease: a preliminary study

    Directory of Open Access Journals (Sweden)

    Jimenez-Sousa Ma

    2012-07-01

    Full Text Available Abstract Background Chronic kidney disease progression has been linked to pro-inflammatory cytokines and markers of inflammation. These markers are also elevated in end-stage renal disease (ESRD, which constitutes a serious public health problem. Objective To investigate whether single nucleotide polymorphisms (SNPs located in genes related to immune and inflammatory processes, could be associated with ESRD development. Design and methods A retrospective case-control study was carried out on 276 patients with ESRD and 288 control subjects. Forty-eight SNPs were genotyped via SNPlex platform. Logistic regression was used to assess the relationship between each sigle polymorphism and the development of ESRD. Results Four polymorphisms showed association with ESRD: rs1801275 in the interleukin 4 receptor (IL4R gene (OR: 0.66 (95%CI = 0.46-0.95; p = 0.025; overdominant model, rs4586 in chemokine (C-C motif ligand 2 (CCL2 gene (OR: 0.70 (95%CI = 0.54-0.90; p = 0.005; additive model, rs301640 located in an intergenic binding site for signal transducer and activator of transcription 4 (STAT4 (OR: 1.82 (95%CI = 1.17-2.83; p = 0.006; additive model and rs7830 in the nitric oxide synthase 3 (NOS3 gene (OR: 1.31 (95%CI = 1.01-1.71; p = 0.043; additive model. After adjusting for multiple testing, results lost significance. Conclusion Our preliminary data suggest that four genetic polymorphisms located in genes related to inflammation and immune processes could help to predict the risk of developing ESRD.

  16. Featured Article: Differential regulation of endothelial nitric oxide synthase phosphorylation by protease-activated receptors in adult human endothelial cells.

    Science.gov (United States)

    Tillery, Lakeisha C; Epperson, Tenille A; Eguchi, Satoru; Motley, Evangeline D

    2016-03-01

    Protease-activated receptors have been shown to regulate endothelial nitric oxide synthase through the phosphorylation of specific sites on the enzyme. It has been established that PAR-2 activation phosphorylates eNOS-Ser-1177 and leads to the production of the potent vasodilator nitric oxide, while PAR-1 activation phosphorylates eNOS-Thr-495 and decreases nitric oxide production in human umbilical vein endothelial cells. In this study, we hypothesize a differential coupling of protease-activated receptors to the signaling pathways that regulates endothelial nitric oxide synthase and nitric oxide production in primary adult human coronary artery endothelial cells. Using Western Blot analysis, we showed that thrombin and the PAR-1 activating peptide, TFLLR, lead to the phosphorylation of eNOS-Ser-1177 in human coronary artery endothelial cells, which was blocked by SCH-79797 (SCH), a PAR-1 inhibitor. Using the nitrate/nitrite assay, we also demonstrated that the thrombin- and TFLLR-induced production of nitric oxide was inhibited by SCH and L-NAME, a NOS inhibitor. In addition, we observed that TFLLR, unlike thrombin, significantly phosphorylated eNOS-Thr-495, which may explain the observed delay in nitric oxide production in comparison to that of thrombin. Activation of PAR-2 by SLIGRL, a PAR-2 specific ligand, leads to dual phosphorylation of both catalytic sites but primarily regulated eNOS-Thr-495 phosphorylation with no change in nitric oxide production in human coronary artery endothelial cells. PAR-3, known as the non-signaling receptor, was activated by TFRGAP, a PAR-3 mimicking peptide, and significantly induced the phosphorylation of eNOS-Thr-495 with minimal phosphorylation of eNOS-Ser-1177 with no change in nitric oxide production. In addition, we confirmed that PAR-mediated eNOS-Ser-1177 phosphorylation was Ca(2+)-dependent using the Ca(2+) chelator, BAPTA, while eNOS-Thr-495 phosphorylation was mediated via Rho kinase using the ROCK inhibitor, Y-27632

  17. Lmx1b controls peptide phenotypes in serotonergic and dopaminergic neurons

    Institute of Scientific and Technical Information of China (English)

    Rui Yan; Tianwen Huang; Zhiqin Xie; Guannan Xia; Hui Qian; Xiaolin Zhao; Leping Cheng

    2013-01-01

    Serotonin (5-HT) neurons synthesize a variety of peptides.How these peptides are controlled during development remains unclear.It has been reported that the co-localization of peptides and 5-HT varies by species.In contrast to the situations in the rostral 5-HT neurons of human and rat brains,several peptides do not coexist with 5-HT in the rostral 5-HT neurons of mouse brain.In this study,we found that the peptide substance P and peptide genes,including those encoding peptides thyrotropin-releasing hormone,enkephalin,and calcitonin gene-related peptide,were expressed in the caudal 5-HT neurons of mouse brain; these findings are in line with observations in rat and monkey 5-HT neurons.We also revealed that these peptides/peptide genes partially overlapped with the transcription factor Lmx1b that specifies the 5-HT cell fate.Furthermore,we found that the peptide cholecystokinin was expressed in developing dopaminergic neurons and greatly overlapped with Lmx1b that specifies the dopaminergic cell fate.By examining the phenotype of Lmx1b deletion mice,we found that Lmx1b was required for the expression of above peptides expressed in 5-HT or dopaminergic neurons.Together,our results indicate that Lmx1b,a key transcription factor for the specification of 5-HT and dopaminergic transmitter phenotypes during embryogenesis,determines some peptide phenotypes in these neurons as well.

  18. Identifying Novel Candidate Genes Related to Apoptosis from a Protein-Protein Interaction Network

    Directory of Open Access Journals (Sweden)

    Baoman Wang

    2015-01-01

    Full Text Available Apoptosis is the process of programmed cell death (PCD that occurs in multicellular organisms. This process of normal cell death is required to maintain the balance of homeostasis. In addition, some diseases, such as obesity, cancer, and neurodegenerative diseases, can be cured through apoptosis, which produces few side effects. An effective comprehension of the mechanisms underlying apoptosis will be helpful to prevent and treat some diseases. The identification of genes related to apoptosis is essential to uncover its underlying mechanisms. In this study, a computational method was proposed to identify novel candidate genes related to apoptosis. First, protein-protein interaction information was used to construct a weighted graph. Second, a shortest path algorithm was applied to the graph to search for new candidate genes. Finally, the obtained genes were filtered by a permutation test. As a result, 26 genes were obtained, and we discuss their likelihood of being novel apoptosis-related genes by collecting evidence from published literature.

  19. Nitric oxide and the enigma of cardiac hypertrophy.

    Science.gov (United States)

    Kempf, Tibor; Wollert, Kai C

    2004-06-01

    In pathological conditions associated with persistent increases in hemodynamic workload (old myocardial infarction, high blood pressure, valvular heart disease), a number of signalling pathways are activated in the heart, all of which promote hypertrophic growth of the heart, characterised at the cellular level by increases in individual cardiac myocyte size. Some of these pathways are required for a successful adaptation to cardiac injury. Other pathways are maladaptive, however, as they lead to progressive contractile dysfunction and heart failure. The free radical gas nitric oxide and natriuretic peptides, both of which are produced in the heart, have emerged as endogenous inhibitors of maladaptive hypertrophy signalling. Overall, it appears that cardiac hypertrophy is controlled by an interplay of pro- and antihypertrophic signalling networks. This delicate balance can tip towards adaptation or heart failure. In the future, patients living with cardiac disease may benefit from therapeutic strategies targeting maladaptive hypertrophy signalling pathways. Copyright 2004 Wiley Periodicals, Inc.

  20. Endomorphin-suppressed nitric oxide release from mice peritoneal macrophages.

    Science.gov (United States)

    Balog, Tihomir; Sarić, Ana; Sobocanec, Sandra; Kusić, Borka; Marotti, Tatjana

    2010-02-01

    Endomorphins are newly discovered mu-opioid receptor selective immunocompetent opioid peptides. Endomorphin 1 is predominantly distributed in brain, while endomorphin 2 is widely allocated in the spinal cord. Lately, endomorphins have been investigated as modulators of reactive oxygen and nitrogen species. Nitric oxide is short lived radical involved in various biological processes such as regulation of blood vessel contraction, inflammation, neurotransmission and apoptosis. The aim of this work was to investigate the in vivo effects of endomorphins on nitric oxide release and NOS 2 isoenzyme upregulation in mice peritoneal macrophages additionally challenged ex vivo with lipopolysaccharide. The results showed that endomorphin 1 or endomorphin 2 in vitro did not change NO release from peritoneal mouse macrophages during a 48 h incubation period. On the other hand in vivo endomorphins had suppressive effect on NO release as well as on NOS 2 and IL-1 protein concentration. The most of suppressive effect in vivo of both endomorphins was blocked with 30 min pretreatment with mu-receptor selective antagonist beta-FNA, which proved involvement of opioid receptor pathway in suppressive effects of endomorphins.

  1. Inducible nitric oxide synthase in renal transplantation

    NARCIS (Netherlands)

    Joles, JA; Vos, IH; Grone, HJ; Rabelink, TJ

    2002-01-01

    The importance of the endothelial isoform of nitric oxide synthase (eNOS) has been well established. Endothelium-derived nitric oxide has been shown to be essential for vascular homeostasis and modulation of eNOS has thus become a target in prevention of cardiovascular disease. The role of the induc

  2. Nitric oxide fumigation for postharvest pest control

    Science.gov (United States)

    Nitric oxide fumigation is effective against all arthropod pests at various life stages tested. Nine insect pests at various life stages and bulb mites were subjected to nitric oxide fumigation treatments under ultralow oxygen conditions of =50 ppm O2 in 1.9L glass jars as fumigation chambers. The ...

  3. Human peptide transporters

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Brodin, Birger; Jørgensen, Flemming Steen

    2002-01-01

    Peptide transporters are epithelial solute carriers. Their functional role has been characterised in the small intestine and proximal tubules, where they are involved in absorption of dietary peptides and peptide reabsorption, respectively. Currently, two peptide transporters, PepT1 and PepT2, wh...

  4. Human peptide transporters

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Brodin, Birger; Jørgensen, Flemming Steen;

    2002-01-01

    Peptide transporters are epithelial solute carriers. Their functional role has been characterised in the small intestine and proximal tubules, where they are involved in absorption of dietary peptides and peptide reabsorption, respectively. Currently, two peptide transporters, PepT1 and PepT2...

  5. CGRP receptors mediating CGRP-, adrenomedullin- and amylin-induced relaxation in porcine coronary arteries. Characterization with 'Compound 1' (WO98/11128), a non-peptide antagonist

    DEFF Research Database (Denmark)

    Hasbak, P; Sams, A; Schifter, S

    2001-01-01

    1. Calcitonin gene-related peptide (CGRP), amylin and adrenomedullin (AM) belong to the same family of peptides. Accumulating evidence indicate that the calcitonin (CT) receptor, the CT receptor-like receptor (CRLR) and receptor-activity-modifying proteins (RAMPs) form the basis of all the recept......1. Calcitonin gene-related peptide (CGRP), amylin and adrenomedullin (AM) belong to the same family of peptides. Accumulating evidence indicate that the calcitonin (CT) receptor, the CT receptor-like receptor (CRLR) and receptor-activity-modifying proteins (RAMPs) form the basis of all....... The partial porcine mRNA sequences shared 82 - 92% nucleotide identity with human sequences. 3. The human peptides alphaCGRP, betaCGRP, AM and amylin induced relaxation with pEC(50) values of 8.1, 8.1, 6.7 and 6.1 M respectively. 4. The antagonistic properties of a novel non-peptide CGRP antagonist 'Compound...

  6. Resveratrol and Endothelial Nitric Oxide

    Directory of Open Access Journals (Sweden)

    Ning Xia

    2014-10-01

    Full Text Available Nitric oxide (NO derived from the endothelial NO synthase (eNOS has antihypertensive, antithrombotic, anti-atherosclerotic and antiobesogenic properties. Resveratrol is a polyphenol phytoalexin with multiple cardiovascular and metabolic effects. Part of the beneficial effects of resveratrol are mediated by eNOS. Resveratrol stimulates NO production from eNOS by a number of mechanisms, including upregulation of eNOS expression, stimulation of eNOS enzymatic activity and reversal of eNOS uncoupling. In addition, by reducing oxidative stress, resveratrol prevents oxidative NO inactivation by superoxide thereby enhancing NO bioavailability. Molecular pathways underlying these effects of resveratrol involve SIRT1, AMPK, Nrf2 and estrogen receptors.

  7. Do endogenous opioids and nitric oxide participate in the anticonvulsant action of dipyrone?

    Directory of Open Access Journals (Sweden)

    G.M.L. Reis

    2003-09-01

    Full Text Available It was previously reported that systemic administration of dipyrone inhibited the tonic component of generalized tonic-clonic seizures in both the electroshock and the audiogenic seizure models. The aim of the present study was to investigate the mechanisms involved in the anticonvulsant action of dipyrone by assessing the role of nitric oxide and opioids in the electroshock (female 60- to 90-day-old Wistar rats, N = 5-11 and audiogenic seizure (female 60- to 90-day-old Wistar audiogenic rats, N = 5-11 models of epilepsy. Naloxone (5 mg/kg, sc significantly reversed the anticonvulsant effect of dipyrone in rats submitted to the induction of audiogenic seizures (ANOVA/Bonferroni's test, suggesting the involvement of opioid peptides in this action. In the electroshock model no reversal of the anticonvulsant effect of dipyrone by naloxone (5 mg/kg, sc was demonstrable. The acute (120 mg/kg, ip and chronic (25 mg/kg, ip, twice a day/4 days administration of L-NOARG did not reverse the anticonvulsant action of dipyrone in the audiogenic seizure model, suggesting that the nitric oxide pathway does not participate in such effect. Indomethacin (10, 20 and 30 mg/kg, ip used for comparison had no anticonvulsant effect in the audiogenic seizure model. In conclusion, opioid peptides but not nitric oxide seem to be involved in the anticonvulsant action of dipyrone in audiogenic seizures.

  8. Nitric oxide and chronic colitis

    Directory of Open Access Journals (Sweden)

    Matthew B Grisham

    1996-01-01

    Full Text Available Nitric oxide (NO is thought to play an important role in modulating the inflammatory response by virtue of its ability to affect bloodflow, leukocyte function and cell viability. The objective of this study was to assess the role that NO may play in mediating the mucosal injury and inflammation in a model of chronic granulomatous colitis using two pharmacologically different inhibitors of nitric oxide synthase (NOS. Chronic granulomatous colitis with liver and spleen inflammation was induced in female Lewis rats via the subserosal (intramural injection of peptidoglycan/polysaccharide (PG/PS derived from group A streptococci. Chronic NOS inhibition by oral administration of NG-nitro-L-arginine methyl ester (L-NAME (15 µmol/kg/day or amino-guanidine (AG (15 µmol/ kg/day was found to attenuate the PG/PS-induced increases in macroscopic colonic inflammation scores and colonic myeloperoxidase activity. Only AG -- not L-NAME – attenuated the PG/PS-induced increases in colon dry weight. Both L-NAME and AG significantly attenuated the PG/PS-induced increases in spleen weight whereas neither was effective at significantly attenuating the PG/PS-induced increases in liver weight. Although both L-NAME and AG inhibited NO production in vivo, as measured by decreases in plasma nitrite and nitrate levels, only AG produced significantly lower values (38±3 versus 83±8 µM, respectively, P<0.05. Finally, L-NAME, but not AG, administration significantly increased mean arterial pressure from 83 mmHg in colitic animals to 105 mmHg in the PG/PS+ L-NAME-treated animals (P<0.05. It is concluded that NO may play an important role in mediating some of the pathophysiology associated with this model of chronic granulomatous colitis.

  9. Intravenous beta-endorphin administration fails to alter hypothalamic blood flow in rats expressing normal or reduced nitric oxide synthase activity

    NARCIS (Netherlands)

    Benyo, Z.; Szabo, C; Velkel, M.H; Bohus, B.G J; Wahl, M.A; Sandor, P

    1996-01-01

    beta-Endorphin (beta-END) significantly contributes to the maintenance of hypothalamic blood flow (HBF) autoregulation during hemorrhagic hypotension in rats. Recently, several natural and synthetic opioid peptides were reported to induce nitric oxide (NO)-mediated dilation in the cerebrovascular

  10. Experimental research on nitric oxide and the therapy of Alzheimer disease: a challenging bridge.

    Science.gov (United States)

    Siciliano, Raffaella; Barone, Eugenio; Calabrese, Vittorio; Rispoli, Vincenzo; Butterfield, D Allan; Mancuso, Cesare

    2011-11-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by severe cognitive impairment due to neuronal death. Although the lost of cognitive function is the main problem for AD subjects, death occurs due to secondary issues such as concomitant infections, respiratory complications or multi-organ failure. Current drugs used in AD are acetylcholinesterase inhibitors and antagonists of the N-methyl-D-aspartate receptor. These drugs may only slightly improve cognitive functions but have only very limited impact on the clinical course of the disease. Over the last 5 years, new targets were identified and innovative drugs against AD have been designed and developed. Worthy of mention are β-secretase inhibitors, monoclonal antibodies against amyloid-β-peptide and tau inhibitors. However, although promising beneficial effects were highlighted in the data from preclinical studies, only few of these new drugs improved cognitive functions for a significant time frame in AD subjects. Controversial is the therapeutic effect on AD obtained through the manipulation of the nitric oxide synthase/nitric oxide system since the potential toxic effects on brain function could overcome the beneficial effects. The aim of this review is to analyze from a pharmacologic point of view both old and new drugs developed for the treatment of AD. In addition, the risk/benefit ratio related to the modulation of the nitric oxide synthase/nitric oxide system in AD brain will be analyzed.

  11. 21 CFR 868.2380 - Nitric oxide analyzer.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nitric oxide analyzer. 868.2380 Section 868.2380...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2380 Nitric oxide analyzer. (a) Identification. The nitric oxide analyzer is a device intended to measure the concentration of nitric oxide...

  12. 21 CFR 862.3080 - Breath nitric oxide test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Breath nitric oxide test system. 862.3080 Section... Systems § 862.3080 Breath nitric oxide test system. (a) Identification. A breath nitric oxide test system is a device intended to measure fractional nitric oxide in human breath. Measurement of changes...

  13. Extracting microRNA-gene relations from biomedical literature using distant supervision.

    Science.gov (United States)

    Lamurias, Andre; Clarke, Luka A; Couto, Francisco M

    2017-01-01

    Many biomedical relation extraction approaches are based on supervised machine learning, requiring an annotated corpus. Distant supervision aims at training a classifier by combining a knowledge base with a corpus, reducing the amount of manual effort necessary. This is particularly useful for biomedicine because many databases and ontologies have been made available for many biological processes, while the availability of annotated corpora is still limited. We studied the extraction of microRNA-gene relations from text. MicroRNA regulation is an important biological process due to its close association with human diseases. The proposed method, IBRel, is based on distantly supervised multi-instance learning. We evaluated IBRel on three datasets, and the results were compared with a co-occurrence approach as well as a supervised machine learning algorithm. While supervised learning outperformed on two of those datasets, IBRel obtained an F-score 28.3 percentage points higher on the dataset for which there was no training set developed specifically. To demonstrate the applicability of IBRel, we used it to extract 27 miRNA-gene relations from recently published papers about cystic fibrosis. Our results demonstrate that our method can be successfully used to extract relations from literature about a biological process without an annotated corpus. The source code and data used in this study are available at https://github.com/AndreLamurias/IBRel.

  14. Polymorphisms in the genes related to angiogenesis are associated with uterine cervical cancer.

    Science.gov (United States)

    Ramos-Flores, Christian; Romero-Gutiérrez, Teresa; Delgado-Enciso, Iván; Maldonado, Gabriela Enríquez; Plascencia, Víctor Montaño; Vazquez-Vuelvas, Oscar F; Quintero-Ramos, Antonio; Mejía, Roberto Chaparro; Espinoza-Gomez, Francisco; Baltazar-Rodriguez, Luz M; Valdez-Velazquez, Laura L

    2013-09-01

    The expression of plasminogen activator inhibitor type 1 (PAI-1), vascular endothelial growth factor (VEGF), and transforming growth factor β1 (TGF-β1) participates in the angiogenesis of several cancer types. The goal of this study was to investigate polymorphisms in genes related to angiogenesis (PAI-1-675 4G/5G, VEGF C936T, and TGF-β1 G-800A) to evaluate the risk for developing uterine cervical cancer (UCC). In a case-control study, 100 healthy subjects and 100 patients with UCC from Mexico were included. We determined the genetic profile of the polymorphic markers, which were evaluated by polymerase chain reaction using a sequence-specific primer. There was no statistical difference in the allele distribution from the intergroup comparisons of PAI-1 675 4G/5G and VEGF C936T data; however, a significant difference was observed within TGF-β1 G-800A. The linkage disequilibrium analysis revealed that PAI-1 -675 4G and TGF-β1 -800A pair-haplotype was in strong linkage disequilibrium with a significantly increased risk (odds ratio, 3.44; 95% confidence interval, 1.66-7.25) to UCC. The polymorphisms in the genes related to angiogenesis -675 4G/5G PAI-1 and G-800A TGF-β1, segregated solely or combined, might contribute to the increased susceptibility to UCC in a Mexican population.

  15. Extracting microRNA-gene relations from biomedical literature using distant supervision

    Science.gov (United States)

    Clarke, Luka A.; Couto, Francisco M.

    2017-01-01

    Many biomedical relation extraction approaches are based on supervised machine learning, requiring an annotated corpus. Distant supervision aims at training a classifier by combining a knowledge base with a corpus, reducing the amount of manual effort necessary. This is particularly useful for biomedicine because many databases and ontologies have been made available for many biological processes, while the availability of annotated corpora is still limited. We studied the extraction of microRNA-gene relations from text. MicroRNA regulation is an important biological process due to its close association with human diseases. The proposed method, IBRel, is based on distantly supervised multi-instance learning. We evaluated IBRel on three datasets, and the results were compared with a co-occurrence approach as well as a supervised machine learning algorithm. While supervised learning outperformed on two of those datasets, IBRel obtained an F-score 28.3 percentage points higher on the dataset for which there was no training set developed specifically. To demonstrate the applicability of IBRel, we used it to extract 27 miRNA-gene relations from recently published papers about cystic fibrosis. Our results demonstrate that our method can be successfully used to extract relations from literature about a biological process without an annotated corpus. The source code and data used in this study are available at https://github.com/AndreLamurias/IBRel. PMID:28263989

  16. Electrochemical Behavior of Aluminum in Nitric Acid

    Institute of Scientific and Technical Information of China (English)

    CHEN; Hui; ZHU; Li-yang; LIN; Ru-shan; TAN; Hong-bin; HE; Hui

    2013-01-01

    Aluminum is one of cladding materials for nuclear fuel,it is important to investigate the electrolytic dissolution of aluminum in nitric acid.The electrochemical impedance spectroscopy,polarization curve and cyclic voltammetry cure of anodic aluminum electrode in nitric acid under various conditions were collected(Fig.1).It turns out,under steady state,the thickness of the passivated film of aluminum

  17. PeptideAtlas

    Data.gov (United States)

    U.S. Department of Health & Human Services — PeptideAtlas is a multi-organism, publicly accessible compendium of peptides identified in a large set of tandem mass spectrometry proteomics experiments. Mass...

  18. Peptide Nucleic Acids (PNA)

    DEFF Research Database (Denmark)

    2002-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  19. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    1998-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  20. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2003-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  1. Antimicrobial Peptides in 2014

    Directory of Open Access Journals (Sweden)

    Guangshun Wang

    2015-03-01

    Full Text Available This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms.

  2. Peptide Nucleic Acid Synthons

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  3. Peptide-Carrier Conjugation

    DEFF Research Database (Denmark)

    Hansen, Paul Robert

    2015-01-01

    To produce antibodies against synthetic peptides it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined....

  4. PH dependent adhesive peptides

    Science.gov (United States)

    Tomich, John; Iwamoto, Takeo; Shen, Xinchun; Sun, Xiuzhi Susan

    2010-06-29

    A novel peptide adhesive motif is described that requires no receptor or cross-links to achieve maximal adhesive strength. Several peptides with different degrees of adhesive strength have been designed and synthesized using solid phase chemistries. All peptides contain a common hydrophobic core sequence flanked by positively or negatively charged amino acids sequences.

  5. Alternative to Nitric Acid Passivation

    Science.gov (United States)

    Kessel, Kurt R.

    2015-01-01

    The Ground Systems Development and Operations (GSDO) Program at NASA John F. Kennedy Space Center (KSC), Florida, has the primary objective of modernizing and transforming the launch and range complex at KSC to benefit current and future NASA programs along with other emerging users. Described as the launch support and infrastructure modernization program in the NASA Authorization Act of 2010, the GSDO Program will develop and implement shared infrastructure and process improvements to provide more flexible, affordable, and responsive capabilities to a multi-user community. In support of NASA and the GSDO Program, the objective of this project is to qualify citric acid as an environmentally-preferable alternative to nitric acid for passivation of stainless steel alloys. This project is a direct follow-on to United Space Alliance (USA) work at KSC to optimize the parameters for the use of citric acid and verify effectiveness. This project will build off of the USA study to further evaluate citric acids effectiveness and suitability for corrosion protection of a number of stainless steels alloys used by NASA, the Department of Defense (DoD), and the European Space Agency (ESA).

  6. Nitric oxide bioavailability in malaria.

    Science.gov (United States)

    Sobolewski, Peter; Gramaglia, Irene; Frangos, John; Intaglietta, Marcos; van der Heyde, Henri C

    2005-09-01

    Rational development of adjunct or anti-disease therapy for severe Plasmodium falciparum malaria requires cellular and molecular definition of malarial pathogenesis. Nitric oxide (NO) is a potential target for such therapy but its role during malaria is controversial. It has been proposed that NO is produced at high levels to kill Plasmodium parasites, although the unfortunate consequence of elevated NO levels might be impaired neuronal signaling, oxidant damage and red blood cell damage that leads to anemia. In this case, inhibitors of NO production or NO scavengers might be an effective adjunct therapy. However, increasing amounts of evidence support the alternate hypothesis that NO production is limited during malaria. Furthermore, the well-documented NO scavenging by cell-free plasma hemoglobin and superoxide, the levels of which are elevated during malaria, has not been considered. Low NO bioavailability in the vasculature during malaria might contribute to pathologic activation of the immune system, the endothelium and the coagulation system: factors required for malarial pathogenesis. Therefore, restoring NO bioavailability might represent an effective anti-disease therapy.

  7. Down regulation of gene related sex hormone synthesis pathway in mouse testes by miroestrol and deoxymiroestrol.

    Science.gov (United States)

    Udomsuk, Latiporn; Juengwatanatrakul, Thaweesak; Putalun, Waraporn; Jarukamjorn, Kanokwan

    2011-12-01

    Miroestrol and deoxymiroestrol are phytoestrogens isolated from tuberous root of Pueraria candollei var. mirifica. Modulatory effects of miroestrol and deoxymiroestrol on enzymes involved in sex-hormone synthesis pathway in male C57BL/6 mice were investigated using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Miroestrol and deoxymiroestrol suppressed the expressions of 3β-HSD, 17β-HSD1, and CYP17 while CYP19 mRNA expression was slightly decreased. In addition, the expression of 17β-HSD2 was induced in correlation with those did by estradiol. These observations supported that miroestrol and deoxymiroestrol could exhibit the same effect as estradiol regarding regulation of testicular gene related sex hormone synthesis pathway.

  8. [Progress in genes related to seed-coat color in soybean].

    Science.gov (United States)

    Song, Jian; Guo, Yong; Yu, Li-Jie; Qiu, Li-Juan

    2012-06-01

    Seed-coat color has changed from black to yellow during natural and artificial selection of cultivated soybean from wild soybean, and it is also an important morphological marker. Therefore, discovering genes related to the soybean seed-coat color will play a very important role in breeding and evolutionary study. Different seed-coat colors caused by deposition of various anthocyanin pigments. Although pigmentation has been well dissected at molecular level in several plant species, the genes controlling natural variation of seed-coat color in soybean remain to be unknown. Genes related to seed-coat color in soybean were discussed in this paper, including 5 genetic loci (I, T, W1, R and O). Locus I is located in a region that riches in chalcone synthase (CHS) genes on chromosome 8. Gene CHS is a multi-gene family with highly conserved sequences in soybean. Locus T located on chromosome 6 has been cloned and verified, which encodes a flavon-oid-3'-hydroxylase. Mutant of F3'H can not interact with the heme-binding domain due to lack of conservative domain GGEK caused by a nucleotide deletion in the coding region of F3'H. Locus R is located between A668-1 and K387-1 on chromosome 9 (linkage group K). This locus may encode a R2R3 MYB transcription factor or a UDP flavonoid 3-O glyco-syltransferase. Locus O is located between Satt207 and Satt493 on chromosome 8 (linkage group A2) and its molecular characteristics has not been characterized. Locus W1 may be a homology of F3'5'H gene.

  9. Inducible nitric oxide synthase is responsible for nitric oxide release from murine pituicytes

    DEFF Research Database (Denmark)

    Kjeldsen, T H; Rivier, C; Lee, S;

    2003-01-01

    This study investigated whether pituicytes were able to produce and release nitric oxide (NO), and which type of nitric oxide synthase (NOS) would be responsible for this phenomenon. Lipopolysaccharide (LPS) 1 micro g/ml was used as inflammatory mediator. Because pituicytes are known to secrete...

  10. Protective Effect of Wheat Peptides against Indomethacin-Induced Oxidative Stress in IEC-6 Cells

    Directory of Open Access Journals (Sweden)

    Hong Yin

    2014-01-01

    Full Text Available Recent studies have demonstrated that wheat peptides protected rats against non-steroidal anti-inflammatory drugs-induced small intestinal epithelial cells damage, but the mechanism of action is unclear. In the present study, an indomethacin-induced oxidative stress model was used to investigate the effect of wheat peptides on the nuclear factor-κB(NF-κB-inducible nitric oxide synthase-nitric oxide signal pathway in intestinal epithelial cells-6 cells. IEC-6 cells were treated with wheat peptides (0, 125, 500 and 2000 mg/L for 24 h, followed by 90 mg/L indomethacin for 12 h. Wheat peptides significantly attenuated the indomethacin-induced decrease in superoxide dismutase and glutathione peroxidase activity. Wheat peptides at 2000 mg/L markedly decreased the expression of the NF-κB in response to indomethacin-induced oxidative stress. This study demonstrated that the addition of wheat peptides to a culture medium significantly inhibited the indomethacin-induced release of malondialdehyde and nitrogen monoxide, and increased antioxidant enzyme activity in IEC-6 cells, thereby providing a possible explanation for the protective effect proposed for wheat peptides in the prevention of indomethacin-induced oxidative stress in small intestinal epithelial cells.

  11. Protective effect of wheat peptides against indomethacin-induced oxidative stress in IEC-6 cells.

    Science.gov (United States)

    Yin, Hong; Pan, Xingchang; Song, Zhixiu; Wang, Shaokang; Yang, Ligang; Sun, Guiju

    2014-01-29

    Recent studies have demonstrated that wheat peptides protected rats against non-steroidal anti-inflammatory drugs-induced small intestinal epithelial cells damage, but the mechanism of action is unclear. In the present study, an indomethacin-induced oxidative stress model was used to investigate the effect of wheat peptides on the nuclear factor-κB(NF-κB)-inducible nitric oxide synthase-nitric oxide signal pathway in intestinal epithelial cells-6 cells. IEC-6 cells were treated with wheat peptides (0, 125, 500 and 2000 mg/L) for 24 h, followed by 90 mg/L indomethacin for 12 h. Wheat peptides significantly attenuated the indomethacin-induced decrease in superoxide dismutase and glutathione peroxidase activity. Wheat peptides at 2000 mg/L markedly decreased the expression of the NF-κB in response to indomethacin-induced oxidative stress. This study demonstrated that the addition of wheat peptides to a culture medium significantly inhibited the indomethacin-induced release of malondialdehyde and nitrogen monoxide, and increased antioxidant enzyme activity in IEC-6 cells, thereby providing a possible explanation for the protective effect proposed for wheat peptides in the prevention of indomethacin-induced oxidative stress in small intestinal epithelial cells.

  12. Nitric oxide, inducible nitric oxide synthase and inflammation in veterinary medicine.

    Science.gov (United States)

    Hunter, Robert P

    2002-12-01

    Inflammation is a process consisting of a complex of cytological and chemical reactions which occur in and around affected blood vessels and adjacent tissues in response to an injury caused by a physical, chemical or biological insult. Much work has been performed in the past several years investigating inducible nitric oxide synthase (NOS, EC 1.14.13.39) and nitric oxide in inflammation. This has resulted in a rapid increase in knowledge about iNOS and nitric oxide. Nitric oxide formation from inducible NOS is regulated by numerous inflammatory mediators, often with contradictory effects, depending upon the type and duration of the inflammatory insult. Equine medicine appears to have benefited the most from the increased interest in this small, inflammatory mediator. Most of the information on nitric oxide in traditional veterinary species has been produced using models or naturally occurring inflammatory diseases of this species.

  13. Nitric Oxide Homeostasis in Neurodegenerative Diseases.

    Science.gov (United States)

    Hannibal, Luciana

    2016-01-01

    The role of nitric oxide in the pathogenesis and progression of neurodegenerative illnesses such as Parkinson's and Alzheimer's diseases has become prominent over the years. Increased activity of the enzymes that produce reactive oxygen species, decreased activity of antioxidant enzymes and imbalances in glutathione pools mediate and mark the neurodegenerative process. Much of the oxidative damage of proteins is brought about by the overproduction of nitric oxide by nitric oxide synthases (NOS) and its subsequent reactivity with reactive oxygen species. Proteomic methods have advanced the field tremendously, by facilitating the quantitative assessment of differential expression patterns and oxidative modifications of proteins and alongside, mapping their non-canonical functions. As a signaling molecule involved in multiple biochemical pathways, the level of nitric oxide is subject to tight regulation. All three NOS isoforms display aberrant patterns of expression in Alzheimer's disease, altering intracellular signaling and routing oxidative stress in directions that are uncompounded. This review discusses the prime factors that control nitric oxide biosynthesis, reactivity footprints and ensuing effects in the development of neurodegenerative diseases.

  14. Useful and harmful effects of nitric oxide

    Directory of Open Access Journals (Sweden)

    Jović Slavoljub

    2013-01-01

    Full Text Available In living sistems synthesis of nitric oxide occurs during metabolism from Larginin, nitrite and ascorbate. Being very significant carrier of information within numerous both physiological and pathological proceses in mammals' organisms, nitric oxid could possibly be useful as well as harmful. Nitric oxide synthesis is adjuvant in a healthy organism because it represents the basic molecule for understanding numerous processes in neurology, psychology, immunology and varios related fields. In other words, nitric oxide participate in number of physiological processes, such as: transmission of nerve signals (neurotransmitter role, regulation of smooth muscle tissue relaxation (eg. vasodilatation, peristaltic movements, immunomodulation, mastocyte activation, development of inflammatory response, apoptosis regulation, angiogenesis and glucose metabolism, normal heart functioning and antioxidation role. Besides being useful, nitric oxide can be harmful as well, because it has one unpaired electron, so consequently it is susceptible to oxidation becoming a stable free radical. Being such, it reacts quickly with superoxide-anion radical, givind at first an extremely reactive peroxinitrite anion, and subsequently peroxidnitrite acid. This acid is very dangerous causing thiol groups oxidation, tyrosine and phenylalanine nitrosylation, lipid oxidation, DNK chain splitting, nitrification and nucleic bases deamination. These damages of macromolecules can cause a series of undesirable changes which subsequently distub functions of molecules, and thus of cells, tissues and even organs. [Projekat Ministarstva nauke Republike Srbije, br. 173034 i br. 31085

  15. Sumatriptan down-regulates calcitonin gene-related peptide expression via extracellular signalregulated 1/2 and c-Jun N-terminal kinase signaling transduction pathways in rat trigeminal ganglion after organ culture%舒马普坦通过细胞外信号调节激酶1/2和c-Jun氨基末端激酶信号通路下调三叉神经节内降钙素基因相关肽的表达

    Institute of Scientific and Technical Information of China (English)

    罗国刚; 袁博博; 樊文静; 袁兴运; 霍康; 吕社民; 曹永孝; 徐仓宝

    2012-01-01

    Objective To explore the effects of sumatriptan on the modulation of calcitonin generelated peptide(CGRP) expression and its involving intracellular signaling transduction mechanisms in rat trigeminal ganglion(TG) after organ culture.Methods Using organ culture in vitro model,54 isolated TGs of SD rats were randomly divided into fresh group ( n =6 ),control group ( n =6 ) and experimental group (n =42,6 TGs for each subgroup).Experimental group included seven subgroups,which were respectively pretreated with four different concentrations of sumatriptan,specific inhibitors of extracellular signalregulated kinases 1/2 (ERK1/2) pathway (U0126 and PD98059 ),and the inhibitor of c-Jun N-terminal kinase (JNK) (SP600125).After co-cultured with above intervention agents for 24 h,CGRP-immunoreactivity (CGRP-ir) positive neurons and CGRP-mRNA expression levels were quantified by immunohistoehemistry stain and real-time polymerase chain reaction,respectively.Phosphorylated ERK1/2 (pERK1/2) and JNK (pJNK) proteins levels were determined by Western-blotting method.Results The CGRP-ir ( + ) neurons expression levels were significantly increased after 24 h organ culture.However,0.10 and 0.50 mg/ml concentrations of sumatriptan remarkably decreased the CGRP-ir ( + ) neurons expression levels.The positive cell percentage,positive optic area,integrated optical density,mean optical density and CGRP-mRNA expression level in TG were significantly reduced than control groups (tPCP =8.652,26.382; tarea =6.220,13.917; tIA =5.606,15.904; tM14 =2.661,21.748; tmRNA =8.032,15.675.P < 0.05 ).The CGRP-mRNA expressions were significantly down-regulated after co-incubation with concentration of 0.50 mg/ml sumatriptan for 24 h in TG of SD rat ( P <0.05 ).The levels of pERK1/2 and pJNK protein kinase detected by Western-blotting were significantly reduced by 0.50 mg/ml concentration of sumatriptan,the degrees of which were closed to the ERK1/2 and JNK pathway specific blockers.Conclusion It

  16. Identification of Peptides Inhibiting Adhesion of Monocytes to the Injured Vascular Endothelial Cells through Phage-displaying Screening

    Institute of Scientific and Technical Information of China (English)

    Yu GUO; Jia ZHANG; Ji-Cheng WANG; Feng-Xiang YAN; Bing-Yang ZHU; Hong-Lin HUANG; Duan-Fang LIAO

    2005-01-01

    Using oxidized low-density lipoprotein (LDL)-injured vascular endothelial cells (ECs) as target cells, peptides specifically binding to the injured ECs were screened from a phage-displaying peptide library by using the whole-cell screening technique after three cycles of the "adsorption-elution-amplification"procedure. Positive phage clones were identified by ELISA, and the inserted amino acid sequences in the displaying peptides were deduced from confirmation with DNA sequencing. The adhesion rate of ECs to monocytes was evaluated by cell counting. The activity of endothelial nitric oxide synthase (eNOS), and the expression levels of caveolin- 1 and intercellular adhesion molecule- 1 (ICAM- 1) were determined by Western blotting. Six positive clones specifically binding to injured ECV304 endothelial cells were selected from fourteen clones. Interestingly, four phages had peptides with tandem leucine, and two of these even shared an identical sequence. Functional analysis demonstrated that the YCPRYVRRKLENELLVL peptide shared by two clones inhibited the expression of ICAM-1, increased nitric oxide concentration in the culture media, and upregulated the expression of caveolin-1 and eNOS. As a result, the adhesion rate of monocytes to ECV304 cells was significantly reduced by 12.1%. These data suggest that the anti-adhesion effect of these novel peptides is related to the regulation of the caveolin-1/nitric oxide signal transduction pathway, and could be of use in potential therapeutic agents against certain cardiovascular diseases initiated by vascular endothelial cell damage.

  17. [Nitric oxide and lipid peroxidation].

    Science.gov (United States)

    Cristol, J P; Maggi, M F; Guérin, M C; Torreilles, J; Descomps, B

    1995-01-01

    Nitric oxide (NO) is a free radical produced enzymatically in biological systems from the guanidino group of L-arginine. Its large spectrum of biological effects is achieved through chemical interactions with different targets including oxygen (O2), superoxide (O2o-) and other oxygen reactive species (ROS), transition metals and thiols. Superoxide anions and other ROS have been reported to react with NO to produce peroxynitrite anions that can decompose to form nitrogen dioxide (NO2) and hydroxyl radial (OHo). Thus, NO has been reported to have a dual effect on lipid peroxidation (prooxidant via the peroxynitrite or antioxydant via the chelation of ROS). In the present study we have investigated in different models the in vitro and in vivo action of NO on lipid peroxidation. Copper-induced LDL oxidation were used as an in vitro model. Human LDL (100 micrograms ApoB/ml) were incubated in oxygene-saturated PBS buffer in presence or absence of Cu2+ (2.5 microM) with increasing concentrations of NO donnors (sodium nitroprussiate or nitroso-glutathione). LDL oxidation was monitored continuously for conjugated diene formation (234 nm) and 4-hydroxynonenal (HNE) accumulation. Exogenous NO prevents in a dose dependent manner the progress of copper-induced oxidation. Ischaemia-reperfusion injury (I/R), characterized by an overproduction of ROS, is used as an in vivo model. Anaesthetized rats were submitted to 1 hour renal ischaemia following by 2 hours of reperfusion. Sham-operated rats (SOP) were used as control. Lipid peroxidation was evaluated by measuring the HNE accumulated in rats kidneys in presence or absence of L-arginine or D-arginine infusion. L-arginine, but not D-arginine, enhances HNE accumulation in I/R but not in SOP (< 0.050 pmol/g tissue in SOP versus 0.6 nmol/g tissue in I/R), showing that, in this experimental conditions, NO produced from L-arginine, enhances the toxicity of ROS. This study shows that the pro- or antioxydant effects of NO are different

  18. Nitrate tolerance impairs nitric oxide-mediated vasodilation in vivo

    DEFF Research Database (Denmark)

    Laursen, Jørn Bech; Boesgaard, Søren; Poulsen, Henrik E.;

    1996-01-01

    Nitrates, Nitrate tolerence, Nitric oxide, acetylcholine, N-acetylcholine, N-acetylcysteine, L-NAME, Rat, Anesthetized......Nitrates, Nitrate tolerence, Nitric oxide, acetylcholine, N-acetylcholine, N-acetylcysteine, L-NAME, Rat, Anesthetized...

  19. Identification of differentially expressed genes related to aphid resistance in cucumber (Cucumis sativus L.).

    Science.gov (United States)

    Liang, Danna; Liu, Min; Hu, Qijing; He, Min; Qi, Xiaohua; Xu, Qiang; Zhou, Fucai; Chen, Xuehao

    2015-05-11

    Cucumber, a very important vegetable crop worldwide, is easily damaged by pests. Aphids (Aphis gossypii Glover) are among the most serious pests in cucumber production and often cause severe loss of yield and make fruit quality get worse. Identifying genes that render cucumbers resistant to aphid-induced damage and breeding aphid-resistant cucumber varieties have become the most promising control strategies. In this study, a Illumina Genome Analyzer platform was applied to monitor changes in gene expression in the whole genome of the cucumber cultivar 'EP6392' which is resistant to aphids. Nine DGE libraries were constructed from infected and uninfected leaves. In total, 49 differentially expressed genes related to cucumber aphid resistance were screened during the treatment period. These genes are mainly associated with signal transduction, plant-pathogen interactions, flavonoid biosynthesis, amino acid metabolism and sugar metabolism pathways. Eight of the 49 genes may be associated with aphid resistance. Finally, expression of 9 randomly selected genes was evaluated by qRT-PCR to verify the results for the tag-mapped genes. With the exception of 1-aminocyclopropane-1-carboxylate oxidase homolog 6, the expression of the chosen genes was in agreement with the results of the tag-sequencing analysis patterns.

  20. Study of the influence of genes related to muscle oxidative processes on beef color.

    Science.gov (United States)

    Falomir-Lockhart, A H; Rogberg-Muñoz, A; Papaleo-Mazzucco, J; Goszczynski, D E; Lirón, J P; Fernández, M E; Añon, M C; Melucci, L M; Giovambattista, G

    2015-10-01

    The biochemical bases of meat color are determined by the concentration and redox state of myoglobin, hemoglobin, cytochromes, and other pigments. Post-mortem depletion of cellular oxygen results in oxidative stresses that consume NADH and affects reducing activity, while enzymatic detoxification influences the cellular oxidative processes, both affecting meat color. The aim of this work was to study the influence of several genes related to cellular oxidative processes that could affect CIELAB meat color parameters. The study was performed in steers that received a grass-based diet combined with grain, hays and silages. Results suggest a possible link between colorimetric parameters (a*, b* and chroma) and SNPs in the GSTP1 gene (P<0.05). Although the influence of the enzymes, encoded by GSTP1 gene, on meat color has been proposed previously at biochemical level and protein expression level, further association studies in different populations and functional studies of proteins are needed to confirm the genetic determination of that gene on meat color.

  1. Identification of genes related to intramuscular fat content of pig using genome-wide association study.

    Science.gov (United States)

    Won, Sohyoung; Jung, Jaehoon; Park, Eungwoo; Kim, H B

    2017-06-27

    The aim of this study is to identify SNPs and genes related to pig IMF and estimate the heritability of IMF. Genome-wide association study (GWAS) on 704 inbred Berkshires was performed for intramuscular fat content (IMF). To consider the inbreeding among samples, associations of the SNPs with IMF were tested as random effects in a mixed linear model using the genetic relationship matrix by GEMMA. Significant genes were compared with reported pig IMF QTL regions and functional classification of the identified genes were also performed. Heritability of IMF was estimated by GCTA tool. Total 365 SNPs were found to be significant from a cutoff of p-value IMF QTL regions. BMPER, FOXO1, EDAR, RNF149, CD40, PTPN1, SOX9, MYC, MIF were related to mitogen-activated protein kinase (MAPK) pathway which regulates the differentiation to adipocytes. These genes and the genes mapped on QTLs could be the candidate genes affecting IMF. Heritability of IMF was estimated as 0.52, which was relatively high, suggesting that a considerable portion of the total variance of IMF is explained by the SNP information. Our results can contribute to breeding pig with better IMF and therefore, producing pork with better sensory qualities.

  2. Identification of Genes Related to Paulownia Witches’ Broom by AFLP and MSAP

    Directory of Open Access Journals (Sweden)

    Xibing Cao

    2014-08-01

    Full Text Available DNA methylation is believed to play important roles in regulating gene expression in plant growth and development. Paulownia witches’ broom (PaWB infection has been reported to be related to gene expression changes in paulownia plantlets. To determine whether DNA methylation is associated with gene expression changes in response to phytoplasma, we investigated variations in genomic DNA sequence and methylation in PaWB plantlets treated with methyl methane sulfonate (MMS using amplified fragment length polymorphism (AFLP and methylation-sensitive amplification polymorphism (MSAP techniques, respectively. The results indicated that PaWB seedings recovered a normal morphology after treatment with more than 15 mg·L−1 MMS. PaWB infection did not cause changes of the paulownia DNA sequence at the AFLP level; However, DNA methylation levels and patterns were altered. Quantitative real-time PCR (qRT-PCR showed that three of the methylated genes were up-regulated and three were down-regulated in the MMS-treated PaWB plantlets that had regained healthy morphology. These six genes might be involved in transcriptional regulation, plant defense, signal transduction and energy. The possible roles of these genes in PaWB are discussed. The results showed that changes of DNA methylation altered gene expression levels, and that MSAP might help identify genes related to PaWB.

  3. Identification of genes related to Paulownia witches' broom by AFLP and MSAP.

    Science.gov (United States)

    Cao, Xibing; Fan, Guoqiang; Deng, Minjie; Zhao, Zhenli; Dong, Yanpeng

    2014-08-21

    DNA methylation is believed to play important roles in regulating gene expression in plant growth and development. Paulownia witches' broom (PaWB) infection has been reported to be related to gene expression changes in paulownia plantlets. To determine whether DNA methylation is associated with gene expression changes in response to phytoplasma, we investigated variations in genomic DNA sequence and methylation in PaWB plantlets treated with methyl methane sulfonate (MMS) using amplified fragment length polymorphism (AFLP) and methylation-sensitive amplification polymorphism (MSAP) techniques, respectively. The results indicated that PaWB seedings recovered a normal morphology after treatment with more than 15 mg·L(-1) MMS. PaWB infection did not cause changes of the paulownia DNA sequence at the AFLP level; However, DNA methylation levels and patterns were altered. Quantitative real-time PCR (qRT-PCR) showed that three of the methylated genes were up-regulated and three were down-regulated in the MMS-treated PaWB plantlets that had regained healthy morphology. These six genes might be involved in transcriptional regulation, plant defense, signal transduction and energy. The possible roles of these genes in PaWB are discussed. The results showed that changes of DNA methylation altered gene expression levels, and that MSAP might help identify genes related to PaWB.

  4. Epilepsy in Rett syndrome, and CDKL5- and FOXG1-gene-related encephalopathies.

    Science.gov (United States)

    Guerrini, Renzo; Parrini, Elena

    2012-12-01

    Rett syndrome is an X-linked neurodevelopmental disorder that manifests in early childhood with developmental stagnation, and loss of spoken language and hand use, with the development of distinctive hand stereotypies, severe cognitive impairment, and autistic features. About 60% of patients have epilepsy. Seizure onset before the age of 3 years is unlikely, and onset after age 20 is rare. Diagnosis of Rett syndrome is based on key clinical elements that identify "typical" Rett syndrome but also "variant" or "atypical" forms. Diagnostic criteria have been modified only slightly over time, even after discovering that MECP2 gene alterations are present in >90% of patients with typical Rett syndrome but only in 50-70% of atypical cases. Over the last several years, intragenic or genomic alterations of the CDKL5 and FOXG1 genes have been associated with severe cognitive impairment, early onset epilepsy and, often, dyskinetic movement disorders, which have variably been defined as Rett variants. It is now clearly emerging that epilepsy has distinctive characteristics in typical Rett syndrome and in the different syndromes caused by CDKL5 and FOXG1 gene alterations. The progressive parting of CDKL5- and FOXG1-gene-related encephalopathies from the core Rett syndrome is reflected by the effort to produce clearer diagnostic criteria for typical and atypical Rett syndrome. Efforts to characterize the molecular pathology underlying these developmental encephalopathies are pointing to abnormalities of telencephalic development, neuronal morphogenesis, maturation and maintenance, and dendritic arborization.

  5. miRTex: A Text Mining System for miRNA-Gene Relation Extraction.

    Science.gov (United States)

    Li, Gang; Ross, Karen E; Arighi, Cecilia N; Peng, Yifan; Wu, Cathy H; Vijay-Shanker, K

    2015-01-01

    MicroRNAs (miRNAs) regulate a wide range of cellular and developmental processes through gene expression suppression or mRNA degradation. Experimentally validated miRNA gene targets are often reported in the literature. In this paper, we describe miRTex, a text mining system that extracts miRNA-target relations, as well as miRNA-gene and gene-miRNA regulation relations. The system achieves good precision and recall when evaluated on a literature corpus of 150 abstracts with F-scores close to 0.90 on the three different types of relations. We conducted full-scale text mining using miRTex to process all the Medline abstracts and all the full-length articles in the PubMed Central Open Access Subset. The results for all the Medline abstracts are stored in a database for interactive query and file download via the website at http://proteininformationresource.org/mirtex. Using miRTex, we identified genes potentially regulated by miRNAs in Triple Negative Breast Cancer, as well as miRNA-gene relations that, in conjunction with kinase-substrate relations, regulate the response to abiotic stress in Arabidopsis thaliana. These two use cases demonstrate the usefulness of miRTex text mining in the analysis of miRNA-regulated biological processes.

  6. Impact of C-Myc gene-related aberrations in newly diagnosed myeloma with bortezomib/dexamethasone therapy.

    Science.gov (United States)

    Sekiguchi, Naohiro; Ootsubo, Kaori; Wagatsuma, Miyuki; Midorikawa, Kiyoe; Nagata, Akihisa; Noto, Satoshi; Yamada, Kazuaki; Takezako, Naoki

    2014-03-01

    Recent studies have suggested that c-Myc over-expression may be a factor indicating poor prognosis in multiple myeloma (MM), although c-Myc gene-related abnormalities, including translocation and gene amplification, have not been fully investigated in the novel agent era. Additional chromosome 8 may be considered as aggressive disease in the 1990s. To clarify the impact of these aberrations, we retrospectively analyzed newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM) with bortezomib and dexamethasone induction therapy. In the present study, the high-risk group was defined as having at least one of the following present: non-hyperdiploidy, IgH/FGFR3, and del p53. Forty NDMM cases were analyzed. At the median follow-up duration of 14.1 months, 14 RRMM were recognized. The proportions of patients in the high-risk, c-Myc gene-related aberrations, and additional chromosome 8 groups at diagnosis were 45.5, 22.5, and 10 %, respectively. The proportions of patients who developed RRMM in the high-risk, c-Myc gene-related aberrations, and additional chromosome 8 groups were 41.7, 77.7, and 50 %, respectively. Furthermore, patients with c-Myc gene-related abnormalities tended to exhibit inferior progression-free survival (PFS), and those with c-Myc gene-related abnormalities and/or additional chromosome 8 showed statistically shorter PFS. Therefore, c-Myc gene-related abnormalities and additional chromosome 8 may be related to a poorer prognosis.

  7. Acylation of Therapeutic Peptides

    DEFF Research Database (Denmark)

    Trier, Sofie; Henriksen, Jonas Rosager; Jensen, Simon Bjerregaard

    peptides are similar in size and structure, but oppositely charged at physiological pH. Both peptides were acylated with linear acyl chains of systematically increasing length, where sCT was furthermore acylated at two different positions on the peptide backbone. For GLP-2, we found that increasing acyl...... stems from a synergy between the positive peptide charge and membrane-active acyl moiety, supported by its pH-dependency, whereby the effect increased with decreasing pH and concomitant charge increase. The extent of permeation enhancing effect was highly dependent on acylation chain length and position...

  8. Topical peptides as cosmeceuticals

    Directory of Open Access Journals (Sweden)

    Varadraj Vasant Pai

    2017-01-01

    Full Text Available Peptides are known to have diverse biological roles, most prominently as signaling/regulatory molecules in a broad variety of physiological processes including defense, immunity, stress, growth, homeostasis and reproduction. These aspects have been used in the field of dermatology and cosmetology to produce short, stable and synthetic peptides for extracellular matrix synthesis, pigmentation, innate immunity and inflammation. The evolution of peptides over the century, which started with the discovery of penicillin, has now extended to their usage as cosmeceuticals in recent years. Cosmeceutical peptides may act as signal modulators of the extracellular matrix component, as structural peptides, carrier peptides and neurotransmitter function modulators. Transdermal delivery of peptides can be made more effective by penetration enhancers, chemical modification or encapsulation of peptides. The advantages of using peptides as cosmeceuticals include their involvement in many physiological functions of the skin, their selectivity, their lack of immunogenicity and absence of premarket regulatory requirements for their use. However, there are disadvantages: clinical evidence for efficacy is often weak, absorption may be poor due to low lipophilicity, high molecular weight and binding to other ingredients, and prices can be quite high.

  9. Exercise training upregulates nitric oxide synthases in the kidney of rats with chronic heart failure.

    Science.gov (United States)

    Ito, Daisuke; Ito, Osamu; Mori, Nobuyoshi; Cao, Pengyu; Suda, Chihiro; Muroya, Yoshikazu; Hao, Kiyotaka; Shimokawa, Hiroaki; Kohzuki, Masahiro

    2013-09-01

    There is an interaction between heart and kidney diseases, which is a condition termed cardiorenal syndrome. Exercise training has cardioprotective effects, involving upregulation of endothelial (e) nitric oxide synthase (NOS) in the cardiovascular system. However, the effects of exercise training on NOS in the kidney with heart disease are unknown. The aim of the present study was to investigate whether exercise training upregulates NOS in the kidney, left ventricle and aorta of rats with chronic heart failure (CHF). Male Sprague-Dawley rats underwent left coronary artery ligation (LCAL) to induce CHF and were randomly assigned to sedentary or treadmill exercise groups 4 weeks after LCAL. Three days after exercising for 4 weeks, urine samples were collected for 24 h and blood samples were collected following decapitation. Nitric oxide synthase activity and protein expression were examined. Significant interactions between CHF and exercise training were observed on parameters of cardiac and renal function. Exercise training improved cardiac function, decreased plasma B-type natriuretic peptide levels, decreased urinary albumin excretion and increased creatinine clearance in CHF rats. Nitric oxide synthase activity, eNOS expression and neuronal (n) NOS expression were significantly decreased in the left ventricle and kidney of CHF rats. Exercise training significantly increased NOS activity and eNOS and nNOS expression. Upregulation of NOS in the kidney and left ventricle may contribute, in part, to the renal and cardiac protective effects of exercise training in cardiorenal syndrome in CHF rats.

  10. 21 CFR 868.5165 - Nitric oxide administration apparatus.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nitric oxide administration apparatus. 868.5165... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5165 Nitric oxide administration apparatus. (a) Identification. The nitric oxide administration apparatus is a device used to add...

  11. CHANGES OF NITRIC OXIDE AND PROTECTIVE EFFECTS OF NITRIC OXIDE INHIBITORS IN NEWBORN RATS WITH SEPSIS

    Institute of Scientific and Technical Information of China (English)

    史源; 李华强; 潘捷; 沈际皋

    1995-01-01

    In a newborn rat model of sepsis, the changes of nitric oxide and the protective effects of methylene blue or/and dexaraethason were investigated. The results revealed that plasma nitric oxide levels were ele-cted at 6 h and peaked at 12 h after bacterial challenge. The treatment with methylene or/and dexam-etbasone was found to Munt hypoglycenua and hyperlacdcemla, to reduce the occurrence rate of loss ot re-sponse to pain, and to prolong the survival time. Moreover, therapy by dexamethasone was shown to de-crease the 24 h mortality. The results suggested that nitric coide play an important role during the course of fatal P. aeruginosa sepsis, hut it is clear that the clinical value of nitric oxide and its inhibitors need to be further studied.

  12. Circulating nitric oxide products do not solely reflect nitric oxide release in cirrhosis and portal hypertension

    DEFF Research Database (Denmark)

    Afzelius, Pia; Bazeghi, Nassim; Bie, Peter;

    2011-01-01

    Patients with cirrhosis often develop a systemic vasodilatation and a hyperdynamic circulation with activation of vasoconstrictor systems such as the renin-angiotensin-aldosterone system (RAAS), and vasopressin. Increased nitric oxide (NO) synthesis has been implicated in the development...

  13. Nitric oxide turnover in permeable river sediment

    DEFF Research Database (Denmark)

    Schreiber, Frank; Stief, Peter; Kuypers, Marcel M M

    2014-01-01

    We measured nitric oxide (NO) microprofiles in relation to oxygen (O2) and all major dissolved N-species (ammonium, nitrate, nitrite, and nitrous oxide [N2O]) in a permeable, freshwater sediment (River Weser, Germany). NO reaches peak concentrations of 0.13 μmol L-1 in the oxic zone and is consumed...

  14. Nitric Oxide in Mammary Tumor Progression

    Science.gov (United States)

    1998-07-01

    de Miguel L, Monton M, Casado S, Lopez -Farre A: Endothelial cytosolic proteins bind to the 3’-untranslated region of endothelial nitric oxide...Vazquez AM. Cabrera L, Barral AM, Gen- 38. Morgan DA, Ruscetti FW, Gallo R: Selective in vitro delman R, Jondal M: Toxic effects of interleukin-2

  15. Nitric Oxide Synthase Inhibitors as Antidepressants

    DEFF Research Database (Denmark)

    Wegener, Gregers; Volke, Vallo

    2010-01-01

    been suggested to play major roles in the pathophysiology of mood and stress-related disorders. However, a few clinical and several pre-clinical studies, strongly suggest involvement of the nitric oxide (NO) signaling pathway in these disorders. Moreover, several of the conventional neurotransmitters...

  16. Processes regulating nitric oxide emissions from soils

    DEFF Research Database (Denmark)

    Pilegaard, Kim

    2013-01-01

    Nitric oxide (NO) is a reactive gas that plays an important role in atmospheric chemistry by influencing the production and destruction of ozone and thereby the oxidizing capacity of the atmosphere. NO also contributes by its oxidation products to the formation of acid rain. The major sources...

  17. Nitric Oxide and the Central Nervous System

    NARCIS (Netherlands)

    E. Dzoljic (Eleonora)

    1998-01-01

    textabstractDuring the last ten years, several investigators have reported that biological effects of endothelium-derived relaxing factor (EDRF; Furchgott and Zawadzki, 1980) are actually activities of a signal molecule, nitric oxide (NO; Moncada el al., 1988). This molecule is synthesised by endoth

  18. Gene-network analysis identifies susceptibility genes related to glycobiology in autism.

    Directory of Open Access Journals (Sweden)

    Bert van der Zwaag

    Full Text Available The recent identification of copy-number variation in the human genome has opened up new avenues for the discovery of positional candidate genes underlying complex genetic disorders, especially in the field of psychiatric disease. One major challenge that remains is pinpointing the susceptibility genes in the multitude of disease-associated loci. This challenge may be tackled by reconstruction of functional gene-networks from the genes residing in these loci. We applied this approach to autism spectrum disorder (ASD, and identified the copy-number changes in the DNA of 105 ASD patients and 267 healthy individuals with Illumina Humanhap300 Beadchips. Subsequently, we used a human reconstructed gene-network, Prioritizer, to rank candidate genes in the segmental gains and losses in our autism cohort. This analysis highlighted several candidate genes already known to be mutated in cognitive and neuropsychiatric disorders, including RAI1, BRD1, and LARGE. In addition, the LARGE gene was part of a sub-network of seven genes functioning in glycobiology, present in seven copy-number changes specifically identified in autism patients with limited co-morbidity. Three of these seven copy-number changes were de novo in the patients. In autism patients with a complex phenotype and healthy controls no such sub-network was identified. An independent systematic analysis of 13 published autism susceptibility loci supports the involvement of genes related to glycobiology as we also identified the same or similar genes from those loci. Our findings suggest that the occurrence of genomic gains and losses of genes associated with glycobiology are important contributors to the development of ASD.

  19. 6-Gingerol Protects against Nutritional Steatohepatitis by Regulating Key Genes Related to Inflammation and Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Thing-Fong Tzeng

    2015-02-01

    Full Text Available Non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis (NASH, appears to be increasingly common worldwide. The aim of the study was to investigate the effects of 6-gingerol ((S-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl-3-decanone, a bioactive ingredient of plants belonging to the Zingiberaceae family, on experimental models of NASH. In HepG2 cells, 6-gingerol (100 μmol/L treatment inhibited free fatty acids mixture (0.33 mmol/L palmitate and 0.66 mmol/L oleate-induced triglyceride and inflammatory marker accumulations. Male C57BL/6 mice were fed with a methionine and choline-deficient (MCD diet to induce steatohepatitis. After four weeks of MCD diet feeding, the mice were dosed orally with 6-gingerol (25, 50 or 100 mg/kg/day once daily for another four weeks. 6-Gingerol (100 mg/kg/day attenuated liver steatosis and necro-inflammation in MCD diet-fed mice. The expressions of inflammatory cytokine genes, including those for monocyte chemoattractant protein-1, tumor necrosis factor-α, and interleukin-6, and nuclear transcription factor (NF-κB, which were increased in the livers of MCD diet-fed mice, were attenuated by 6-gingerol. 6-Gingerol possesses a repressive property on hepatic steatosis, which is associated with induction of peroxisome proliferator-activated receptor α. Our study demonstrated the protective role of 6-gingerol in ameliorating nutritional steatohepatitis. The effect was mediated through regulating key genes related to lipid metabolism and inflammation.

  20. Transcriptional and functional studies of Acidithiobacillus ferrooxidans genes related to survival in the presence of copper.

    Science.gov (United States)

    Navarro, Claudio A; Orellana, Luis H; Mauriaca, Cecilia; Jerez, Carlos A

    2009-10-01

    The acidophilic Acidithiobacillus ferrooxidans can resist exceptionally high copper (Cu) concentrations. This property is important for its use in biomining processes, where Cu and other metal levels range usually between 15 and 100 mM. To learn about the mechanisms that allow A. ferrooxidans cells to survive in this environment, a bioinformatic search of its genome showed the presence of at least 10 genes that are possibly related to Cu homeostasis. Among them are three genes coding for putative ATPases related to the transport of Cu (A. ferrooxidans copA1 [copA1(Af)], copA2(Af), and copB(Af)), three genes related to a system of the resistance nodulation cell division family involved in the extraction of Cu from the cell (cusA(Af), cusB(Af), and cusC(Af)), and two genes coding for periplasmic chaperones for this metal (cusF(Af) and copC(Af)). The expression of most of these open reading frames was studied by real-time reverse transcriptase PCR using A. ferrooxidans cells adapted for growth in the presence of high concentrations of Cu. The putative A. ferrooxidans Cu resistance determinants were found to be upregulated when this bacterium was exposed to Cu in the range of 5 to 25 mM. These A. ferrooxidans genes conferred to Escherichia coli a greater Cu resistance than wild-type cells, supporting their functionality. The results reported here and previously published data strongly suggest that the high resistance of the extremophilic A. ferrooxidans to Cu may be due to part or all of the following key elements: (i) a wide repertoire of Cu resistance determinants, (ii) the duplication of some of these Cu resistance determinants, (iii) the existence of novel Cu chaperones, and (iv) a polyP-based Cu resistance system.

  1. Increased nitric oxide release and expression of endothelial and inducible nitric oxide synthases in mildly changed porcine mitral valve leaflets

    DEFF Research Database (Denmark)

    Moesgaard, Sophia G; Olsen, Lisbeth H; Viuff, Birgitte M

    2007-01-01

    BACKGROUND AND AIM OF THE STUDY: Little is known of the local role of nitric oxide (NO) in heart valves in relation to heart valve diseases. The study aim was to examine NO release and the expression of both endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in re...

  2. Increased nitric oxide release and expression of endothelial and inducible nitric oxide synthases in mildly changed porcine mitral valve leaflets

    DEFF Research Database (Denmark)

    Moesgaard, Sophia Gry; Olsen, Lisbeth Høier; Viuff, Birgitte;

    2007-01-01

    Background and aim of the study: Little is known of the local role of nitric oxide (NO) in heart valves in relation to heart valve diseases. The study aim was to examine NO release and the expression of both endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (i...

  3. Insulin C-peptide test

    Science.gov (United States)

    C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin the body produces and insulin someone injects ...

  4. Genetic association analysis of 30 genes related to obesity in a European American population.

    Science.gov (United States)

    Li, P; Tiwari, H K; Lin, W-Y; Allison, D B; Chung, W K; Leibel, R L; Yi, N; Liu, N

    2014-05-01

    Obesity, which is frequently associated with diabetes, hypertension and cardiovascular diseases, is primarily the result of a net excess of caloric intake over energy expenditure. Human obesity is highly heritable, but the specific genes mediating susceptibility in non-syndromic obesity remain unclear. We tested candidate genes in pathways related to food intake and energy expenditure for association with body mass index (BMI). We reanalyzed 355 common genetic variants of 30 candidate genes in seven molecular pathways related to obesity in 1982 unrelated European Americans from the New York Cancer Project. Data were analyzed by using a Bayesian hierarchical generalized linear model. The BMIs were log-transformed and then adjusted for covariates, including age, age(2), gender and diabetes status. The single-nucleotide polymorphisms (SNPs) were modeled as additive effects. With the stipulated adjustments, nine SNPs in eight genes were significantly associated with BMI: ghrelin (GHRL; rs35683), agouti-related peptide (AGRP; rs5030980), carboxypeptidase E (CPE; rs1946816 and rs4481204), glucagon-like peptide-1 receptor (GLP1R; rs2268641), serotonin receptors (HTR2A; rs912127), neuropeptide Y receptor (NPY5R;Y5R1c52), suppressor of cytokine signaling 3 (SOCS3; rs4969170) and signal transducer and activator of transcription 3 (STAT3; rs4796793). We also found a gender-by-SNP interaction (rs1745837 in HTR2A), which indicated that variants in the gene HTR2A had a stronger association with BMI in males. In addition, NPY1R was detected as having a significant gene effect even though none of the SNPs in this gene was significant. Variations in genes AGRP, CPE, GHRL, GLP1R, HTR2A, NPY1R, NPY5R, SOCS3 and STAT3 showed modest associations with BMI in European Americans. The pathways in which these genes participate regulate energy intake, and thus these associations are mechanistically plausible in this context.

  5. Modulatory role of nitric oxide in cardiac performance

    Directory of Open Access Journals (Sweden)

    Smiljić Sonja

    2014-01-01

    Full Text Available Nitric oxide is produced by almost all cardiac cells, endothelial cells, cardiomyocytes and nerve fibers. It is synthesized by an enzyme, a nitric oxide synthase, which occurs in endothelial, neural and inducible form. The distribution of nitric oxide synthase in the heart is characterized by a pronounced non-uniformity. Nitric oxide exerts its effects in physiological and pathophysiological conditions. The physiological effects of low concentrations of nitric oxide, which is released in the normal conditions under the influence of constituent enzymes, occur via cyclic guanosine monophosphate. The synthesized nitric oxide exhibits its effect in the cells where it is produced, in an autocrine manner, or by diffusing into the neighboring cells, in a paracrine manner. Nitric oxide acts by regulating the coronary vessel tonus, affecting the contractility of cardiomyocytes, generating an inotropic effect in a dose-dependent manner and controlling the cellular respiration. Other effects of nitric oxide in the cardiovascular system include the hyperpolarization of the smooth muscle cells in blood vessels, the inhibition of the monocyte adhesion, the inhibition of platelet migration, adhesion and aggregation and the proliferation of smooth muscle cells and fibroblasts. The anti-atherosclerotic effects of nitric oxide are based on these effects. Nitric oxide is a weak free radical in gaseous state, and the cytotoxic and/or the cytoprotective effects of the higher concentrations of nitric oxide are related to the chemical structure of nitric oxide as a free radical. The excessive production of nitric oxide by the activation of inducible nitric oxide synthase can lead to major irregularities in the function of cardiomyocytes and cardiac insufficiency. Understanding the nitric oxide molecular mechanisms of signaling pathways in the heart can provide a new strategic approach to prevention and treatment of cardiovascular diseases.

  6. PNA Peptide chimerae

    DEFF Research Database (Denmark)

    Koch, T.; Næsby, M.; Wittung, P.;

    1995-01-01

    Radioactive labelling of PNA has been performed try linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields.......Radioactive labelling of PNA has been performed try linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields....

  7. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds known as peptide nucleic acids, bind complementary DNA and RNA strands, and generally do so more strongly than the corresponding DNA or RNA strands while exhibiting increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from...

  8. Avian host defense peptides

    NARCIS (Netherlands)

    Cuperus, Tryntsje; Coorens, M.; van Dijk, A.; Haagsman, H.P.

    2013-01-01

    Host defense peptides (HDPs) are important effector molecules of the innate immune system of vertebrates. These antimicrobial peptides are also present in invertebrates, plants and fungi. HDPs display broad-spectrum antimicrobial activities and fulfill an important role in the first line of defense

  9. Bacteriocin Inducer Peptides

    Science.gov (United States)

    Novel peptides produced by bacteriocin-producing bacteria stimulate the production of bacteriocins in vitro. The producer bacteria are cultured in the presence of a novel inducer bacteria and a peptide having a carboxy terminal sequence of VKGLT in order to achieve an increase in bacteriocin produc...

  10. APD: the Antimicrobial Peptide Database

    OpenAIRE

    Wang, Zhe; Wang, Guangshun

    2004-01-01

    An antimicrobial peptide database (APD) has been established based on an extensive literature search. It contains detailed information for 525 peptides (498 antibacterial, 155 antifungal, 28 antiviral and 18 antitumor). APD provides interactive interfaces for peptide query, prediction and design. It also provides statistical data for a select group of or all the peptides in the database. Peptide information can be searched using keywords such as peptide name, ID, length, net charge, hydrophob...

  11. Intrahepatic expression of genes related to metabotropic receptors in chronic hepatitis

    Institute of Scientific and Technical Information of China (English)

    Andrzej Cie(s)la,; Maciej Ku(s)mider,; Agata Faron-Górecka; Marta Dziedzicka-Wasylewska; Monika Bociaga-Jasik; Danuta Owczarek; Irena Cie(c)ko-Michalska

    2012-01-01

    AIM:To screen for genes related to metabotropic receptors that might be involved in the development of chronic hepatitis.METHODS:Assessment of 20 genes associated with metabotropic receptors was performed in liver specimens obtained by punch biopsy from 12 patients with autoimmune and chronic hepatitis type B and C.For this purpose,a microarray with low integrity grade and with oligonucleotide DNA probes complementary to target transcripts was used.Evaluation of gene expression was performed in relation to transcript level,correlation between samples and grouping of clinical parameters used in chronic hepatitis assessment.Clinical markers of chronic hepatitis included alanine and aspartate aminotransferase,γ-glutamyltranspeptidase,alkaline phosphatase and cholinesterase activity,levels of iron ions,total cholesterol,triglycerides,albumin,glucose,hemoglobin,platelets,histological analysis of inflammatory and necrotic status,fibrosis according to METAVIR score,steatosis,as well as anthropometric body mass index,waist/hip index,percentage of adipose tissue and liver size in ultrasound examination.Gender,age,concomitant diseases and drugs were also taken into account.Validation of oligonucleotide microarray gene expression results was done with the use of quantitative real-time polymerase chain reaction (qRT-PCR).RESULTS:The highest (0.002 < P < 0.046) expression among genes encoding main components of metabotropic receptor pathways,such as the a subunit of G-coupled protein,phosphoinositol-dependent protein kinase or arrestin was comparable to that of angiotensinogen synthesized in the liver.Carcinogenesis suppressor genes,such as chemokine ligand 4,transcription factor early growth response protein 1 and lysophosphatidic acid receptor,were characterized by the lowest expression (0.002 < P < 0.046),while the factor potentially triggering hepatic cancer,transcription factor JUN-B,had a 20-fold higher expression.The correlation between expression of genes of

  12. Long-lasting physiological antagonism of calcitonin gene-related peptide towards endothelin-1 in rat mesenteric arteries and human coronary arteries

    DEFF Research Database (Denmark)

    Labruijere, Sieneke; Compeer, Matthijs G; van den Bogaerdt, Antoon J;

    2013-01-01

    Endothelin-1 causes long-lasting contraction via endothelin type A receptor (ETAR) in isolated rat mesenteric arteries (RMA) that cannot be readily terminated by removing the agonist, or by adding the ETAR antagonist BQ123 or the NO donor sodium nitroprusside. It could be terminated by adding cal......-lasting non-selective arterial smooth muscle relaxation that may add to the neuropeptide being a physiological antagonist of arterial effects of ET-1. Long-lasting, washout-resistant ET-1/ETAR interaction does not occur in HCMAs....

  13. Calcitonin Gene Related Peptide and Atherosclerosis%降钙素基因相关肽与动脉粥样硬化

    Institute of Scientific and Technical Information of China (English)

    邢明媚; 韦知樱; 许俊

    2011-01-01

    Atherosclerosis is one of the most common angiopathy in cardiovascular disease,it impacts the system of vascular,immune and metabolism. The occurrence and development of atherosclerosis is a complex process,it damages vascular endothelial,smooth muscle and other cells, involves the interaction of multiple cytokines. CGRP can inhibit vascular smooth muscle and play an important role in the prevention of vascular restenosis, CGRP can relax blood vessels,and play a protective role in prevention and treatment of oxidative stress-induced endothelial cell injury, but the mechanism is not fully understood.%动脉粥样硬化是心血管疾病中最常见的一种血管病变,影响着血管、免疫、代谢等系统.动脉粥样硬化发生发展是一个复杂的过程,它损伤血管内皮,平滑肌等细胞,涉及到多种细胞因子的相互作用.而CGRP具有抑制血管平滑肌增值作用,对预防血管术后再狭窄有重要意义,CGRP能舒张血管,对防治氧化应激引起的内皮损伤具有保护作用,但其机制还不完全清楚.

  14. Comparison of the effects of salmon calcitonin (sCT) and calcitonin gene-related peptide (CGRP) in a number of in vivo and in vitro tests

    Energy Technology Data Exchange (ETDEWEB)

    Welch, S.P.; Brase, D.; Cooper, C.; Dewey, W.L.

    1986-03-05

    sCT and CGRP have been shown previously to have multiple activities in the central nervous system (CNS). Recent work has shown that CGRP (15 ..mu..g) intraventricularly (IVT) produces a naloxone reversible 37% inhibition in the p-phenylquinone test (PPQ) accompanied by severe diarrhea. The ED50 of sCT in the PPQ test is 362 ng and this effect is not reversed totally by naloxone. The onset of CGRP is more rapid than that of sCT. sCT and CGRP (10/sup -6/M) both produce naloxone reversible inhibition of the electrically stimulated guinea pig ileum (GPI) (25% and 50% respectively). Both sCT and CGRP (10/sup -6/ M) produce contracture (15% and 40% respectively) of the non-stimulated GPI that is not blocked by atropine. Both sCT and CGRP block the naloxone-induced contracture of the morphine (MS04) dependent ilea (29% and 68% respectively). Both sCT and CGRP produce biphasic shifts in the MS04 acetylcholine dose-effect curves in the stimulated and nonstimulated GPI, respectively. Neither sCT nor CGRP (10/sup -9/ to 10/sup -4/ M) displaces /sup 3/H-naloxone binding to mouse brain membranes. Both sCT and CGRP may produce their effects by modulation of CA/sup +2/ fluxes in the CNS and GPI.

  15. 4991W93 inhibits release of calcitonin gene-related peptide in the cat but only at doses with 5HT(1B/1D) receptor agonist activity?

    DEFF Research Database (Denmark)

    Knight, Y E; Edvinsson, L; Goadsby, P J

    2001-01-01

    )-mediated effects, that was developed as an anti-migraine drug, and thus was suitable to test whether higher doses of such conformationally restricted triptan analogues could inhibit trigeminal-evoked CGRP release. The superior sagittal sinus (SSS) was stimulated in 14 anaesthetised cats and external jugular vein...

  16. Presence and function of the calcitonin gene-related peptide receptor on rat pial arteries investigated in vitro and in vivo

    DEFF Research Database (Denmark)

    Petersen, K A; Nilsson, E; Olesen, J;

    2005-01-01

    diameter. Only abluminally applied CGRP induced dilation of the cerebral arteries; E(max) for alphaCGRP and betaCGRP were 35 +/- 0.5% and 10.8 +/- 0.2%. These responses were blocked by CGRP(8-37). The gCCW model allowed videomicroscopic visualization of the pial vessels in anaesthetized rats. Changes...

  17. Effect of calcitonin gene-related peptide (CGRP) on motility and on the release of substance P, neurokinin A, somatostatin and gastrin in the isolated perfused porcine antrum

    DEFF Research Database (Denmark)

    Rasmussen, T N; Schmidt, P; Poulsen, S S

    2001-01-01

    release. The effect of pCGRP was unaffected by the addition of the nonpeptide antagonists for the NK-1 (CP-99994) and NK-2 receptors (SR48968), both at 10(-6) mol L(-1), whereas atropine (10(-6) mol L(-1)) completely abolished the motor effect of pCGRP. The release of somatostatin was significantly...

  18. A Novel α-Calcitonin Gene-Related Peptide Analogue Protects Against End-Organ Damage in Experimental Hypertension, Cardiac Hypertrophy and Heart Failure

    DEFF Research Database (Denmark)

    Aubdool, Aisah A; Thakore, Pratish; Argunhan, Fulye

    2017-01-01

    was investigated over 14 days. Blood pressure was measured by radio-telemetry. The ability of the αAnalogue to modulate heart failure was studied in an abdominal aortic constriction (AAC) model of murine cardiac hypertrophy and heart failure over 5 weeks. Extensive ex vivo analysis was performed via RNA analysis...... by reduced hypertrophy and biomarkers of fibrosis, remodelling, inflammation and oxidative stress. In a separate study, the αAnalogue reversed AngII-induced hypertension and associated vascular and cardiac damage. The αAnalogue was effective over 5 weeks in a murine model of cardiac hypertrophy and heart......, Western blot and histology. Results -The AngII-induced hypertension was attenuated by co-treatment with the αAnalogue (50nmol/kg/day, s.c., at a dose selected for lack of long term hypotensive effects at baseline). The αAnalogue protected against vascular, renal and cardiac dysfunction, characterised...

  19. Calcitonin gene-related peptide is released from capsaicin-sensitive nerve fibres and induces vasodilatation of human cerebral arteries concomitant with activation of adenylyl cyclase

    DEFF Research Database (Denmark)

    Jansen-Olesen, I; Mortensen, A; Edvinsson, L

    1996-01-01

    strong and potent relaxation of precontracted circular vessel segments. The Imax (maximum relaxant effect) to human calcitonin was low and the pD2 (concentration for half maximum effect) 7.7 was much lower than that of CGRP. The CGRP-1, antagonist human alpha-CGRP8-37 blocked the response to human alpha......-CGRP but not to human beta-CGRP, while the putative antagonist [Tyr]CGRP28-37 did not. Capsaicin (10(-15)-10(-8)M) caused relaxation of the cerebral arteries by 22% of precontraction. Pre-treatment with 10(-6)M human alpha-CGRP8-37 inhibited this relaxation. Human alpha-CGRP increased the cyclic AMP content of human...... cerebral arteries in a concentration-dependent manner. This increase in adenylyl cyclase activity was blocked by human alpha-CGRP8-37. The results suggest that CGRP-1 receptors coupled to adenylyl cyclase are present in human cerebral arteries....

  20. The Effect of Calcitonin Gene-Related Peptide (CGRP on the Cytosolic Calcium Concentration and Force in Rat Intramural Coronary Arteries

    Directory of Open Access Journals (Sweden)

    M. Sheykhzade

    2001-01-01

    Full Text Available The aim of this study was to investigate the mechanism of CGRP-induced relaxation in intramural rat coronary arteries. By using FURA-2 technique, cytosolic Ca2+-concentration ([Ca2+]i was measured during contraction of the vascular smooth muscle with receptor-dependent agonist (tromboxane A2 analogue U46619 and with high concentration of extracellular potassium. At a steady state of contraction, the increase in [Ca2+]i induced by 300 nM U46619 (100״x 14 nM, n = 7 was similar to that induced by 36 mM K+ (98 ״x 9 nM, n = 7. However, the active tension induced by 300 nM U46619 was significantly (p < 0.01 higher than that induced by 36 mM K+. CGRP concentration-dependently (10 pM - 10 nM reduced both the [Ca2+]i and tension of coronary arteries precontracted with either U46619 or BAY K 8644, and also of resting coronary arteries in PSS. In 36 mM K+-depolarized arteries, CGRP reduced only the tension without affecting the [Ca2+]i. In 300 nM U46619 precontracted arteries, pretreatment with 10 μM thapsigargin significantly (p < 0.05 attenuated the CGRP-induced reduction in the tension (but not [Ca2+]i. In 300 nM U46619 precontracted arteries, pretreatment with either 100 nM charybdotoxin or 100 nM iberiotoxin or 10 nM felodipine significantly (p < 0.05 attenuated the CGRP-induced reduction in both [Ca2+]i and the tension. In contrast, 1 μM glibenclamide did not affect the CGRP-induced responses in these coronary arteries. In resting coronary arteries, only pretreatment with the combination of 1 μM glibenclamide and 100 nM charybdotoxin attenuated the CGRP-induced decrease in the [Ca2+]i and tension, suggesting a different mechanism of action for CGRP in resting coronary arteries. We conclude that CGRP relaxes precontracted rat coronary arteries via three mechanisms: (1 a decrease in [Ca2+]i by inhibiting the Ca2+ influx through membrane hyperpolarization mediated partly by activation of BKCa channels, (2 a decrease in [Ca2+]i presumably by sequestrating cytosolic Ca2+ into thapsigargin-sensitive Ca2+ storage sites, and (3 a decrease in the Ca2+ -sensitivity of the contractile apparatus.

  1. Calcitonin gene-related peptide (CGRP) and its receptor components in human and rat spinal trigeminal nucleus and spinal cord at C1-level

    DEFF Research Database (Denmark)

    Eftekhari, Sajedeh; Edvinsson, Lars

    2011-01-01

    was expressed in fibers of laminae I and II. The CGRP staining was similar in rat, except for CGRP positive neurons that were found close to the central canal. In C1, the receptor components were detected in laminae I and II, however these fibers were distinct from fibers expressing CGRP as verified by confocal...... to regions in the brainstem with Aδ- and C-fibers; this constitutes an essential part of the pain pathways activated in migraine attacks. Therefore it is of importance to identify the regions within the brainstem that processes nociceptive information from the trigeminovascular system, such as the spinal...... trigeminal nucleus (STN) and the C1-level of the spinal cord. Immunohistochemistry was used to study the distribution and relation between CGRP and its receptor components - calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) - in human and rat STN and at the C1-level...

  2. Effects of glyceryl trinitrate and calcitonin-gene-related peptide on BOLD signal and arterial diameter –methodological studies by fMRI and MRA

    DEFF Research Database (Denmark)

    Asghar, Mohammed Sohail; Ashina, Messoud

    2013-01-01

    of measuring task-related hemodynamic changes. Pharmacological substances that induce hemodynamic changes can therefore potentially alter the BOLD-signal that in turn falsely can be interpreted as changes in neuronal activity. It is therefore important to characterize possible effects of a pharmacological......Over the last decades MRI has proved to be very useful in the field of drug development and discovery. Pharmacological MRI (phMRI) explores the interaction between brain physiology, neuronal activity and drugs[1]. The BOLD-signal is an indirect method to investigate brain activity by way...

  3. Descriptors for antimicrobial peptides

    DEFF Research Database (Denmark)

    Jenssen, Håvard

    2011-01-01

    Introduction: A frightening increase in the number of isolated multidrug resistant bacterial strains linked to the decline in novel antimicrobial drugs entering the market is a great cause for concern. Cationic antimicrobial peptides (AMPs) have lately been introduced as a potential new class...... examples of different peptide QSAR studies, this review highlights some of the missing links and illuminates some of the questions that would be interesting to challenge in a more systematic fashion. Expert opinion: Computer-aided peptide QSAR using molecular descriptors may provide the necessary edge...

  4. Speciation in aqueous solutions of nitric acid.

    Science.gov (United States)

    Hlushak, S; Simonin, J P; De Sio, S; Bernard, O; Ruas, A; Pochon, P; Jan, S; Moisy, P

    2013-02-28

    In this study, speciation in aqueous solutions of nitric acid at 25 °C was assessed in two independent ways. First, Raman experiments were carried out and interpreted in terms of free nitrate ions, ion pairs and neutral HNO(3) molecules. In parallel, a model was developed to account for the formation of these two kinds of pairs. It was based on an extension of the binding mean spherical approximation (BiMSA), or associative MSA (AMSA), in which the size and the charge of the ions in the chemical pair may differ from those of the free ions. A simultaneous fit of the osmotic coefficient and of the proportion of free ions (obtained from Raman spectroscopy experiments) led to an estimation of the speciation in nitric acid solutions. The result obtained using this procedure was compared with the estimation obtained from the Raman experiments.

  5. Alternative to Nitric Acid Passivation Project Overview

    Science.gov (United States)

    Lewis, Pattie L.

    2013-01-01

    The standard practice for protection of stainless steel is a process called passivation. This procedure results in the formation of a metal oxide layer to prevent corrosion. Typical passivation procedures call for the use of nitric acid which exhibits excellent corrosion performance; however, there are a number of environmental, worker safety, and operational issues associated with its use. The longtime military specification for the passivation of stainless steel was cancelled in favor of newer specifications which allow for the use of citric acid in place of nitric acid. Citric acid offers a variety of benefits that include increased safety for personnel, reduced environmental impact, and reduced operational costs. There have been few studies, however, to determine whether citric acid is an acceptable alternative for NASA and DoD. This paper details activities to date including development of the joint test plan, on-going and planned testing, and preliminary results.

  6. Endothelial nitric oxide synthase in the microcirculation.

    Science.gov (United States)

    Shu, Xiaohong; Keller, T C Stevenson; Begandt, Daniela; Butcher, Joshua T; Biwer, Lauren; Keller, Alexander S; Columbus, Linda; Isakson, Brant E

    2015-12-01

    Endothelial nitric oxide synthase (eNOS, NOS3) is responsible for producing nitric oxide (NO)--a key molecule that can directly (or indirectly) act as a vasodilator and anti-inflammatory mediator. In this review, we examine the structural effects of regulation of the eNOS enzyme, including post-translational modifications and subcellular localization. After production, NO diffuses to surrounding cells with a variety of effects. We focus on the physiological role of NO and NO-derived molecules, including microvascular effects on vessel tone and immune response. Regulation of eNOS and NO action is complicated; we address endogenous and exogenous mechanisms of NO regulation with a discussion of pharmacological agents used in clinical and laboratory settings and a proposed role for eNOS in circulating red blood cells.

  7. Autoxidation kinetics of aqueous nitric oxide

    OpenAIRE

    1993-01-01

    Reports on the kinetics of the autoxidation of aqueous nitric oxide are discussed. It is concluded that the correct rate law is -d[NO]/dt = 4kaq[NO]2 [O2] with kaq = 2 × 106 M-2 · s-1 at 25°C and that a recent report of a rate law zero order in NO is incorrect. © 1993.

  8. Nitric Oxide Scavenging by Red Cell Microparticles

    OpenAIRE

    Liu, Chen; Zhao, Weixin; George J Christ; Gladwin, Mark T.; Kim-Shapiro, Daniel B.

    2013-01-01

    Red cell microparticles form during the storage of red blood cells and in diseases associated with red cell breakdown and asplenia, including hemolytic anemias such as sickle cell disease. These small phospholipid vesicles that are derived from red blood cells have been implicated in the pathogenesis of transfusion of aged stored blood and hemolytic diseases, via activation of the hemostatic system and effects on nitric oxide (NO) bioavailability. Red cell microparticles react with the import...

  9. Diversity-oriented peptide stapling

    DEFF Research Database (Denmark)

    Tran, Thu Phuong; Larsen, Christian Ørnbøl; Røndbjerg, Tobias

    2017-01-01

    as a powerful method for peptide stapling. However, to date CuAAC stapling has not provided a simple method for obtaining peptides that are easily diversified further. In the present study, we report a new diversity-oriented peptide stapling (DOPS) methodology based on CuAAC chemistry. Stapling of peptides...

  10. Identification of Genes Related to Growth and Lipid Deposition from Transcriptome Profiles of Pig Muscle Tissue.

    Directory of Open Access Journals (Sweden)

    Zhixiu Wang

    Full Text Available Transcriptome profiles established using high-throughput sequencing can be effectively used for screening genome-wide differentially expressed genes (DEGs. RNA sequences (from RNA-seq and microRNA sequences (from miRNA-seq from the tissues of longissimus dorsi muscle of two indigenous Chinese pig breeds (Diannan Small-ear pig [DSP] and Tibetan pig [TP] and two introduced pig breeds (Landrace [LL] and Yorkshire [YY] were examined using HiSeq 2000 to identify and compare the differential expression of functional genes related to muscle growth and lipid deposition. We obtained 27.18 G clean data through the RNA-seq and detected that 18,208 genes were positively expressed and 14,633 of them were co-expressed in the muscle tissues of the four samples. In all, 315 DEGs were found between the Chinese pig group and the introduced pig group, 240 of which were enriched with functional annotations from the David database and significantly enriched in 27 Gene Ontology (GO terms that were mainly associated with muscle fiber contraction, cadmium ion binding, response to organic substance and contractile fiber part. Based on functional annotation, we identified 85 DEGs related to growth traits that were mainly involved in muscle tissue development, muscle system process, regulation of cell development, and growth factor binding, and 27 DEGs related to lipid deposition that were mainly involved in lipid metabolic process and fatty acid biosynthetic process. With miRNA-seq, we obtained 23.78 M reads and 320 positively expressed miRNAs from muscle tissues, including 271 known pig miRNAs and 49 novel miRNAs. In those 271 known miRNAs, 20 were higher and 10 lower expressed in DSP-TP than in LL-YY. The target genes of the 30 miRNAs were mainly participated in MAPK, GnRH, insulin and Calcium signaling pathway and others involved cell development, growth and proliferation, etc. Combining the DEGs and the differentially expressed (DE miRNAs, we drafted a network of 46

  11. Oxygen, nitric oxide and articular cartilage

    Directory of Open Access Journals (Sweden)

    B Fermor

    2007-04-01

    Full Text Available Molecular oxygen is required for the production of nitric oxide (NO, a pro-inflammatory mediator that is associated with osteoarthritis and rheumatoid arthritis. To date there has been little consideration of the role of oxygen tension in the regulation of nitric oxide production associated with arthritis. Oxygen tension may be particularly relevant to articular cartilage since it is avascular and therefore exists at a reduced oxygen tension. The superficial zone exists at approximately 6% O2, while the deep zone exists at less than 1% O2. Furthermore, oxygen tension can alter matrix synthesis, and the material properties of articular cartilage in vitro.The increase in nitric oxide associated with arthritis can be caused by pro-inflammatory cytokines and mechanical stress. Oxygen tension significantly alters endogenous NO production in articular cartilage, as well as the stimulation of NO in response to both mechanical loading and pro-inflammatory cytokines. Mechanical loading and pro-inflammatory cytokines also increase the production of prostaglandin E2 (PGE2. There is a complex interaction between NO and PGE2, and oxygen tension can alter this interaction. These findings suggest that the relatively low levels of oxygen within the joint may have significant influences on the metabolic activity, and inflammatory response of cartilage as compared to ambient levels. A better understanding of the role of oxygen in the production of inflammatory mediators in response to mechanical loading, or pro-inflammatory cytokines, may aid in the development of strategies for therapeutic intervention in arthritis.

  12. Anti-antimicrobial Peptides

    Science.gov (United States)

    Ryan, Lloyd; Lamarre, Baptiste; Diu, Ting; Ravi, Jascindra; Judge, Peter J.; Temple, Adam; Carr, Matthew; Cerasoli, Eleonora; Su, Bo; Jenkinson, Howard F.; Martyna, Glenn; Crain, Jason; Watts, Anthony; Ryadnov, Maxim G.

    2013-01-01

    Antimicrobial or host defense peptides are innate immune regulators found in all multicellular organisms. Many of them fold into membrane-bound α-helices and function by causing cell wall disruption in microorganisms. Herein we probe the possibility and functional implications of antimicrobial antagonism mediated by complementary coiled-coil interactions between antimicrobial peptides and de novo designed antagonists: anti-antimicrobial peptides. Using sequences from native helical families such as cathelicidins, cecropins, and magainins we demonstrate that designed antagonists can co-fold with antimicrobial peptides into functionally inert helical oligomers. The properties and function of the resulting assemblies were studied in solution, membrane environments, and in bacterial culture by a combination of chiroptical and solid-state NMR spectroscopies, microscopy, bioassays, and molecular dynamics simulations. The findings offer a molecular rationale for anti-antimicrobial responses with potential implications for antimicrobial resistance. PMID:23737519

  13. DIA1R is an X-linked gene related to Deleted In Autism-1.

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    Azhari Aziz

    Full Text Available BACKGROUND: Autism spectrum disorders (ASDS are frequently occurring disorders diagnosed by deficits in three core functional areas: social skills, communication, and behaviours and/or interests. Mental retardation frequently accompanies the most severe forms of ASDs, while overall ASDs are more commonly diagnosed in males. Most ASDs have a genetic origin and one gene recently implicated in the etiology of autism is the Deleted-In-Autism-1 (DIA1 gene. METHODOLOGY/PRINCIPAL FINDINGS: Using a bioinformatics-based approach, we have identified a human gene closely related to DIA1, we term DIA1R (DIA1-Related. While DIA1 is autosomal (chromosome 3, position 3q24, DIA1R localizes to the X chromosome at position Xp11.3 and is known to escape X-inactivation. The gene products are of similar size, with DIA1 encoding 430, and DIA1R 433, residues. At the amino acid level, DIA1 and DIA1R are 62% similar overall (28% identical, and both encode signal peptides for targeting to the secretory pathway. Both genes are ubiquitously expressed, including in fetal and adult brain tissue. CONCLUSIONS/SIGNIFICANCE: Examination of published literature revealed point mutations in DIA1R are associated with X-linked mental retardation (XLMR and DIA1R deletion is associated with syndromes with ASD-like traits and/or XLMR. Together, these results support a model where the DIA1 and DIA1R gene products regulate molecular traffic through the cellular secretory pathway or affect the function of secreted factors, and functional deficits cause disorders with ASD-like symptoms and/or mental retardation.

  14. Tumor penetrating peptides

    Directory of Open Access Journals (Sweden)

    Tambet eTeesalu

    2013-08-01

    Full Text Available Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC, contains the integrin-binding RGD motif. RGD mediates tumor homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular zip code of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is

  15. Structural Studies of a Complex Between Endothelial Nitric Oxide Synthase and Calmodulin at Physiological Calcium Concentration.

    Science.gov (United States)

    Piazza, Michael; Dieckmann, Thorsten; Guillemette, Joseph Guy

    2016-10-04

    The small acidic protein Calmodulin (CaM) serves as a Ca(2+) sensor and control element for many enzymes including nitric oxide synthase (NOS) enzymes that play major roles in key physiological and pathological processes. CaM binding causes a conformational change in NOS to allow for the electron transfer between the reductase and oxygenase domains through a process that is thought to be highly dynamic. In this report, NMR spectroscopy was used to determine the solution structure of the endothelial NOS (eNOS) peptide in complex with CaM at the lowest Ca(2+) concentration (225 nM) required for CaM to bind to eNOS and corresponds to a physiological elevated Ca2+ level found in mammalian cells. Under these conditions, the CaM-eNOS complex has a Ca(2+)-replete C-terminal lobe bound the eNOS peptide and a Ca(2+) free N-terminal lobe loosely associated to the eNOS peptide. With increasing Ca(2+) concentration, the binding of Ca(2+) by the N-lobe of CaM results in a stronger interaction with the C-terminal region of the eNOS peptide and increased α-helical structure of the peptide that may be part of the mechanism resulting in electron transfer from the FMN to the heme in the oxygenase domain of the enzyme. SPR studies performed under the same conditions show Ca(2+) concentration dependent binding kinetics were consistent with the NMR structural results. This investigation shows that structural studies performed under more physiological relevant conditions provide information on subtle changes in structure that may not be apparent when experiments are performed in excess Ca(2+) concentrations.

  16. Antimicrobial Peptides in Echinoderms

    OpenAIRE

    Li, C; Haug, T; K Stensvåg

    2010-01-01

    Antimicrobial peptides (AMPs) are important immune effector molecules for invertebrates, including echinoderms, which lack a vertebrate-type adaptive immune system. Here we summarize the knowledge of such peptides in echinoderms. Strongylocins are a novel family of cysteine-rich AMPs, recently identified in the sea urchins, Strongylocentrotus droebachiensis and S. purpuratus. Although these molecules present diverse amino acid sequences, they share an identical cysteine arrangement pattern, d...

  17. Immunotherapy with Allergen Peptides

    OpenAIRE

    Larché Mark

    2007-01-01

    Specific allergen immunotherapy (SIT) is disease-modifying and efficacious. However, the use of whole allergen preparations is associated with frequent allergic adverse events during treatment. Many novel approaches are being designed to reduce the allergenicity of immunotherapy preparations whilst maintaining immunogenicity. One approach is the use of short synthetic peptides which representing dominant T cell epitopes of the allergen. Short peptides exhibit markedly reduced capacity to cro...

  18. Adrenomedullin - new perspectives of a potent peptide hormone.

    Science.gov (United States)

    Schönauer, Ria; Els-Heindl, Sylvia; Beck-Sickinger, Annette G

    2017-02-02

    Adrenomedullin (ADM) is a 52-amino acid multifunctional peptide, which belongs to the calcitonin gene-related peptide (CGRP) superfamily of vasoactive peptide hormones. ADM exhibits a significant vasodilatory potential and plays a key role in various regulatory mechanisms, predominantly in the cardiovascular and lymphatic system. It exerts its effects by activation of the calcitonin receptor-like receptor associated with one of the receptor activity-modifying proteins 2 or 3. ADM was first isolated from human phaeochromocytoma in 1993. Numerous studies revealed a widespread distribution in various tissues and organs, which is reflected by its multiple physiological roles in health and disease. Because of its anti-inflammatory, anti-apoptotic and proliferative properties, ADM exhibits potent protective functions under diverse pathological conditions, but it is also critically involved in tumor progression. ADM has therefore raised great interest in therapeutic applications and several clinical trials already revealed promising results. However, because the receptor activation mode has not yet been fully elucidated, a rational design of potent and selective ligands is still challenging. Detailed information on the binding mode of ADM from a recently reported crystal structure as well as efforts to improve its plasma stability and bioavailability may help to overcome these limitations in the future. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

  19. Updated role of nitric oxide in disorders of erythrocyte function.

    Science.gov (United States)

    Kahn, Marc J; Maley, Jason H; Lasker, George F; Kadowitz, Philip J

    2013-03-01

    Nitric oxide is a potent vasodilator that plays a critical role in disorders of erythrocyte function. Sickle cell disease, paroxysmal nocturnal hemoglobinuria and banked blood preservation are three conditions where nitric oxide is intimately related to dysfunctional erythrocytes. These conditions are accompanied by hemolysis, thrombosis and vasoocclusion. Our understanding of the interaction between nitric oxide, hemoglobin, and the vasculature is constantly evolving, and by defining this role we can better direct trials aimed at improving the treatments of disorders of erythrocyte function. Here we briefly discuss nitric oxide's interaction with hemoglobin through the hypothesis regarding Snitrosohemoglobin, deoxyhemoglobin, and myoglobin as nitrite reductases. We then review the current understanding of the role of nitric oxide in sickle cell disease, paroxysmal nocturnal hemoglobinuria, and banked blood, and discuss therapeutics in development to target nitric oxide in the treatment of some of these disorders.

  20. Genes related to mitochondrial functions are differentially expressed in phosphine-resistant and -susceptible Tribolium castaneum.

    Science.gov (United States)

    Oppert, Brenda; Guedes, Raul N C; Aikins, Michael J; Perkin, Lindsey; Chen, Zhaorigetu; Phillips, Thomas W; Zhu, Kun Yan; Opit, George P; Hoon, Kelly; Sun, Yongming; Meredith, Gavin; Bramlett, Kelli; Hernandez, Natalie Supunpong; Sanderson, Brian; Taylor, Madison W; Dhingra, Dalia; Blakey, Brandon; Lorenzen, Marcé; Adedipe, Folukemi; Arthur, Frank

    2015-11-18

    Phosphine is a valuable fumigant to control pest populations in stored grains and grain products. However, recent studies indicate a substantial increase in phosphine resistance in stored product pests worldwide. To understand the molecular bases of phosphine resistance in insects, we used RNA-Seq to compare gene expression in phosphine-resistant and susceptible laboratory populations of the red flour beetle, Tribolium castaneum. Each population was evaluated as either phosphine-exposed or no phosphine (untreated controls) in triplicate biological replicates (12 samples total). Pairwise analysis indicated there were eight genes differentially expressed between susceptible and resistant insects not exposed to phosphine (i.e., basal expression) or those exposed to phopshine (>8-fold expression and 90 % C.I.). However, 214 genes were differentially expressed among all four treatment groups at a statistically significant level (ANOVA, p < 0.05). Increased expression of 44 cytochrome P450 genes was found in resistant vs. susceptible insects, and phosphine exposure resulted in additional increases of 21 of these genes, five of which were significant among all treatment groups (p < 0.05). Expression of two genes encoding anti-diruetic peptide was 2- to 8-fold reduced in phosphine-resistant insects, and when exposed to phosphine, expression was further reduced 36- to 500-fold compared to susceptible. Phosphine-resistant insects also displayed differential expression of cuticle, carbohydrate, protease, transporter, and many mitochondrial genes, among others. Gene ontology terms associated with mitochondrial functions (oxidation biological processes, monooxygenase and catalytic molecular functions, and iron, heme, and tetrapyyrole binding) were enriched in the significantly differentially expressed dataset. Sequence polymorphism was found in transcripts encoding a known phosphine resistance gene, dihydrolipoamide dehydrogenase, in both susceptible and resistant

  1. An Ongoing Role of α-Calcitonin Gene–Related Peptide as Part of a Protective Network Against Hypertension, Vascular Hypertrophy, and Oxidative Stress

    DEFF Research Database (Denmark)

    Smillie, Sarah-Jane; King, Ross; Kodji, Xenia;

    2014-01-01

    α-Calcitonin gene-related peptide (αCGRP) is a vasodilator, but there is limited knowledge of its long-term cardiovascular protective influence. We hypothesized that αCGRP protects against the onset and development of angiotensin II-induced hypertension and have identified protective mechanisms...

  2. Natriuretic Peptides, Diagnostic and Prognostic Biomarkers

    NARCIS (Netherlands)

    J.H.W. Rutten (Joost)

    2010-01-01

    textabstractIn humans, the natriuretic peptide family consists of three different types of peptides: atrial natriuretic peptide (synonym: atrial natriuretic factor), B-type natriuretic peptide (synonym: brain natriuretic peptide) and C-natriuretic peptide.1 Atrial natriuretic peptide (ANP) was the f

  3. Natriuretic Peptides, Diagnostic and Prognostic Biomarkers

    OpenAIRE

    Rutten, Joost

    2010-01-01

    textabstractIn humans, the natriuretic peptide family consists of three different types of peptides: atrial natriuretic peptide (synonym: atrial natriuretic factor), B-type natriuretic peptide (synonym: brain natriuretic peptide) and C-natriuretic peptide.1 Atrial natriuretic peptide (ANP) was the fi rst natriuretic peptide to be discovered and in humans ANP is predominantly formed in the cardiomyocytes of the atria.2 B-type natriuretic peptide (BNP) was fi rst discovered in porcine brain hen...

  4. Electron transfer in peptides.

    Science.gov (United States)

    Shah, Afzal; Adhikari, Bimalendu; Martic, Sanela; Munir, Azeema; Shahzad, Suniya; Ahmad, Khurshid; Kraatz, Heinz-Bernhard

    2015-02-21

    In this review, we discuss the factors that influence electron transfer in peptides. We summarize experimental results from solution and surface studies and highlight the ongoing debate on the mechanistic aspects of this fundamental reaction. Here, we provide a balanced approach that remains unbiased and does not favor one mechanistic view over another. Support for a putative hopping mechanism in which an electron transfers in a stepwise manner is contrasted with experimental results that support electron tunneling or even some form of ballistic transfer or a pathway transfer for an electron between donor and acceptor sites. In some cases, experimental evidence suggests that a change in the electron transfer mechanism occurs as a result of donor-acceptor separation. However, this common understanding of the switch between tunneling and hopping as a function of chain length is not sufficient for explaining electron transfer in peptides. Apart from chain length, several other factors such as the extent of the secondary structure, backbone conformation, dipole orientation, the presence of special amino acids, hydrogen bonding, and the dynamic properties of a peptide also influence the rate and mode of electron transfer in peptides. Electron transfer plays a key role in physical, chemical and biological systems, so its control is a fundamental task in bioelectrochemical systems, the design of peptide based sensors and molecular junctions. Therefore, this topic is at the heart of a number of biological and technological processes and thus remains of vital interest.

  5. A Comparison of the Effects of Neuronal Nitric Oxide Synthase and Inducible Nitric Oxide Synthase Inhibition on Cartilage Damage

    Directory of Open Access Journals (Sweden)

    Nevzat Selim Gokay

    2016-01-01

    Full Text Available The objective of this study was to investigate the effects of selective inducible nitric oxide synthase and neuronal nitric oxide synthase inhibitors on cartilage regeneration. The study involved 27 Wistar rats that were divided into five groups. On Day 1, both knees of 3 rats were resected and placed in a formalin solution as a control group. The remaining 24 rats were separated into 4 groups, and their right knees were surgically damaged. Depending on the groups, the rats were injected with intra-articular normal saline solution, neuronal nitric oxide synthase inhibitor 7-nitroindazole (50 mg/kg, inducible nitric oxide synthase inhibitor amino-guanidine (30 mg/kg, or nitric oxide precursor L-arginine (200 mg/kg. After 21 days, the right and left knees of the rats were resected and placed in formalin solution. The samples were histopathologically examined by a blinded evaluator and scored on 8 parameters. Although selective neuronal nitric oxide synthase inhibition exhibited significant (P=0.044 positive effects on cartilage regeneration following cartilage damage, it was determined that inducible nitric oxide synthase inhibition had no statistically significant effect on cartilage regeneration. It was observed that the nitric oxide synthase activation triggered advanced arthrosis symptoms, such as osteophyte formation. The fact that selective neuronal nitric oxide synthase inhibitors were observed to have mitigating effects on the severity of the damage may, in the future, influence the development of new agents to be used in the treatment of cartilage disorders.

  6. Anti-tumor activities of peptides corresponding to conserved complementary determining regions from different immunoglobulins.

    Science.gov (United States)

    Figueiredo, Carlos R; Matsuo, Alisson L; Massaoka, Mariana H; Polonelli, Luciano; Travassos, Luiz R

    2014-09-01

    Short synthetic peptides corresponding to sequences of complementarity-determining regions (CDRs) from different immunoglobulin families have been shown to induce antimicrobial, antiviral and antitumor activities regardless of the specificity of the original monoclonal antibody (mAb). Presently, we studied the in vitro and in vivo antitumor activity of synthetic peptides derived from conserved CDR sequences of different immunoglobulins against human tumor cell lines and murine B16F10-Nex2 melanoma aiming at the discovery of candidate molecules for cancer therapy. Four light- and heavy-chain CDR peptide sequences from different antibodies (C36-L1, HA9-H2, 1-H2 and Mg16-H2) showed cytotoxic activity against murine melanoma and a panel of human tumor cell lineages in vitro. Importantly, they also exerted anti-metastatic activity using a syngeneic melanoma model in mice. Other peptides (D07-H3, MN20v1, MS2-H3) were also protective against metastatic melanoma, without showing significant cytotoxicity against tumor cells in vitro. In this case, we suggest that these peptides may act as immune adjuvants in vivo. As observed, peptides induced nitric oxide production in bone-marrow macrophages showing that innate immune cells can also be modulated by these CDR peptides. The present screening supports the search in immunoglobulins of rather frequent CDR sequences that are endowed with specific antitumor properties and may be candidates to be developed as anti-cancer drugs.

  7. Nitric oxide in liver inflammation and regeneration.

    Science.gov (United States)

    Martin-Sanz, Paloma; Hortelano, Sonsoles; Callejas, Nuria A; Goren, Nora; Casado, Marta; Zeini, Miriam; Boscá, Lisardo

    2002-12-01

    Hepatocytes express and release inflammatory mediators after challenge with bacterial cell wall molecules and proinflammatory cytokines. Nitric oxide synthase-2 (NOS-2) is expressed under these conditions and the high-output NO synthesis that follows contributes to the inflammatory response in this tissue and participates in the onset of several hepatopathies. However, in the course of liver regeneration, for example, after partial hepatectomy, NOS-2 is expressed at moderate levels and contributes to inhibit apoptosis and to favor progression in the cell cycle until the organ size and function are restored. The mechanisms involved in the regulation of NOS-2 expression under these conditions are revised.

  8. Nitric oxide and plant iron homeostasis.

    Science.gov (United States)

    Buet, Agustina; Simontacchi, Marcela

    2015-03-01

    Like all living organisms, plants demand iron (Fe) for important biochemical and metabolic processes. Internal imbalances, as a consequence of insufficient or excess Fe in the environment, lead to growth restriction and affect crop yield. Knowledge of signals and factors affecting each step in Fe uptake from the soil and distribution (long-distance transport, remobilization from old to young leaves, and storage in seeds) is necessary to improve our understanding of plant mineral nutrition. In this context, the role of nitric oxide (NO) is discussed as a key player in maintaining Fe homeostasis through its cross talk with hormones, ferritin, and frataxin and the ability to form nitrosyl-iron complexes.

  9. Nitric oxide synthase inhibition and cerebrovascular regulation

    DEFF Research Database (Denmark)

    Iadecola, C; Pelligrino, D A; Moskowitz, M A;

    1994-01-01

    tone and may play an important role in selected vasodilator responses of the cerebral circulation. Furthermore, evidence has been presented suggesting that NO participates in the mechanisms of cerebral ischemic damage. Despite the widespread attention that NO has captured in recent years and the large......There is increasing evidence that nitric oxide (NO) is an important molecular messenger involved in a wide variety of biological processes. Recent data suggest that NO is also involved in the regulation of the cerebral circulation. Thus, NO participants in the maintenance of resting cerebrovascular...

  10. EFFECTS OF NITRIC ACID ON CRITICALITY SAFETY ANALYSIS

    Energy Technology Data Exchange (ETDEWEB)

    Williamson, B.

    2011-08-18

    As nitric acid molarity is increased, there are two competing phenomena affecting the reactivity of the system. First, there is interaction between each of the 10 wells in the basket-like insert. As the molarity of the nitric acid solution is increased (it moves from 100% water to 100% HNO{sub 3}), the hydrogen atom density decreases by about 80%. However, it remains a relatively efficient moderator. The moderating ratio of nitric acid is about 90% that of water. As the media between the wells is changed from 100% water to 100% nitric acid, the density of the media increases by 50%. A higher density typically leads to a better reflector. However, when the macroscopic scattering cross sections are considered, nitric acid is a much worse reflector than water. The effectiveness of nitric acid as a reflector is about 40% that of water. Since the media between the wells become a worse reflector and still remains an effective moderator, interaction between the wells increases. This phenomenon will cause reactivity to increase as nitric acid molarity increases. The seond phenomenon is due to the moderating ratio changing in the high concentration fissile-nitric acid solution in the 10 wells. Since the wells contain relatively small volumes of high concentration solutions, a small decrease in moderating power has a large effect on reactivity. This is due to the fact that neutrons are more likely to escape the high concentration fissile solution before causing another fission event. The result of this phenomenon is that as nitric acid molarity increases, reactivity decreases. Recent studies have shown that the second phenomenon is indeed the dominating force in determining reactivity changes in relation to nitric acid molarity changes. When considering the system as a whole, as nitric acid molarity increases, reactivity decreases.

  11. Dicyclopropylmethyl peptide backbone protectant.

    Science.gov (United States)

    Carpino, Louis A; Nasr, Khaled; Abdel-Maksoud, Adel Ali; El-Faham, Ayman; Ionescu, Dumitru; Henklein, Peter; Wenschuh, Holger; Beyermann, Michael; Krause, Eberhard; Bienert, Michael

    2009-08-20

    The N-dicyclopropylmethyl (Dcpm) residue, introduced into amino acids via reaction of dicyclopropylmethanimine hydrochloride with an amino acid ester followed by sodium cyanoborohydride or triacetoxyborohydride reduction, can be used as an amide bond protectant for peptide synthesis. Examples which demonstrate the amelioration of aggregation effects include syntheses of the alanine decapeptide and the prion peptide (106-126). Avoidance of cyclization to the aminosuccinimide followed substitution of Fmoc-(Dcpm)Gly-OH for Fmoc-Gly-OH in the assembly of sequences containing the sensitive Asp-Gly unit.

  12. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  13. β-PEPTIDES CYCLOBUTANIQUES

    OpenAIRE

    Fernandez, Carlos

    2008-01-01

    The synthesis of β-amino acids, structural analogues of?-Amino acids, is an issue essential in the development of oligopeptides. A lot of work has been conducted on the behavior of β-peptide (sequence of β-amino acids) as well as peptides mixed (mixed β-and β- amino acids). As a result, the conformational preference of β-amino acids will induce the appearance of a three-dimensional structure of the oligopeptide ordered. Thus, several types of helices, sheets and elbows were observed in β-olig...

  14. Immunotherapy with Allergen Peptides

    Directory of Open Access Journals (Sweden)

    Larché Mark

    2007-06-01

    Full Text Available Specific allergen immunotherapy (SIT is disease-modifying and efficacious. However, the use of whole allergen preparations is associated with frequent allergic adverse events during treatment. Many novel approaches are being designed to reduce the allergenicity of immunotherapy preparations whilst maintaining immunogenicity. One approach is the use of short synthetic peptides which representing dominant T cell epitopes of the allergen. Short peptides exhibit markedly reduced capacity to cross link IgE and activate mast cells and basophils, due to lack of tertiary structure. Murine pre-clinical studies have established the feasibility of this approach and clinical studies are currently in progress in both allergic and autoimmune diseases.

  15. Invertebrate FMRFamide related peptides.

    Science.gov (United States)

    Krajniak, Kevin G

    2013-06-01

    In 1977 the neuropeptide FMRFamide was isolated from the clam, Macrocallista nimbosa. Since then several hundred FMRFamide-related peptides (FaRPs) have been isolated from invertebrate animals. Precursors to the FaRPs likely arose in the cnidarians. With the transition to a bilateral body plan FaRPs became a fixture in the invertebrate phyla. They have come to play a critical role as neurotransmitters, neuromodulators, and neurohormones. FaRPs regulate a variety of body functions including, feeding, digestion, circulation, reproduction, movement. The evolution of the molecular form and function of these omnipresent peptides will be considered.

  16. Inducible nitric oxide synthase and guinea-pig ileitis induced by adjuvant

    Directory of Open Access Journals (Sweden)

    N. D. Seago

    1995-01-01

    Full Text Available We sought to establish a model of inflammatory bowel disease by augmenting the activity of the local immune system with Freund's complete adjuvant, and to determine if inducible nitric oxide synthase (iNOS expression and peroxynitrite formation accompanied the inflammatory condition. In anaesthetized guinea-pigs, a loop of distal ileum received intraluminal 50% ethanol followed by Freund's complete adjuvant. Control animals were sham operated. When the animals were killed 7 or 14 days later, loop lavage fluid was examined for nitrite and PGE2 levels; mucosal levels of granulocyte and macrophages were estimated by myeloperoxidase (MPO and N-acetyl-D-glucosaminidase (NAG activity, respectively. Cellular localization if iNOS and peroxynitrite formation were determined by immunohistochemistry with polyclonal antibodies directed against peptide epitopes of mouse iNOS and nitrotyrosine, respectfully. Adjuvant administration resulted in a persistent ileitis, featuring gut thickening, crypt hyperplasia, villus tip swelling and disruption, and cellular infiltration. Lavage levels of PGE2 and nitrite were markedly elevated by adjuvant treatment. Immunoreactive iNOS and nitrotyrosine bordered on detectability in normal animals but were markedly evident with adjuvant treatment at day 7 and particularly day 14. Immunohistochemistry suggested that enteric neurons and epithelia were major sites of iNOS activity and peroxynitrite formation. We conclude that local administration of adjuvant establishes a chronic ileitis. Inducible nitric oxide synthase may contribute to the inflammatory process.

  17. Signal transduction pathways in erythrocyte nitric oxide metabolism under high fibrinogen levels

    Science.gov (United States)

    Saldanha, Carlota; Freitas, T.; Lopez de Almeida, J. P.; Silva-Herdade, A.

    2014-05-01

    Previous studies show that the fibrinogen molecule modulates the metabolism of nitric oxide (NO) in erythrocyte. The in vitro induced hiperfibrinogenemia interferes in the metabolism of the NO in the erythrocyte in dependence of the phosphorylation degree of the band 3. The soluble form of fibrinogen binds into CD47 protein present in the erythrocyte membrane. The soluble thrombomodulin is an inflammatory marker that binds to the erythrocyte CD47 in a site with a sequence peptide known as 4N1K. A study done in vitro shows that when hiperfibrinogenemia was induced in the presence of the peptide 4N1K agonist of CD47 it were observed variations in the efflux of NO from erythrocyte and an increase in the concentrations of GSNO, peroxinitrite, nitrite and nitrate of the erythrocytes. The aim of this work was to study the influence of the peptide 4N1K, on the metabolism of NO in the erythrocyte under high fibrinogen concentration and in the presence of inhibitors of the status of phosphorylation of protein band 3. In this in vitro study, whole blood samples were harvested from healthy subjects and NO, peroxynitrite, nitrite, nitrate and S-nitro-glutathione (GSNO) were determined in presence of 4N1K, calpeptine, Syk inhibitor and under high fibrinogen concentrations. The results obtained in erythrocytes under high fibrinogen levels when 4N1K is present with the Syk inhibitor or with calpeptine, showed in relation to the control samples increased significant concentrations of efflux of NO and of peroxynitrite, nitrite, nitrate and GSNO. In conclusion it was verified that in the in vitro model of hiperfibrinogenemia the peptide 4N1K, agonist of CD47, induces mobilization of NO in the erythrocyte in dependence of the status of phosphorylation of protein band 3.

  18. Adrenoceptor-activated nitric oxide synthesis in salivary acinar cells

    DEFF Research Database (Denmark)

    Looms, Dagnia; Dissing, Steen; Tritsaris, Katerina

    2000-01-01

    We investigated the cellular regulation of nitric oxide synthase (NOS) activity in isolated acinar cells from rat parotid and human labial salivary glands, using the newly developed fluorescent nitric oxide (NO) indicator, DAF-2. We found that sympathetic stimulation with norepinephrine (NE) caus...

  19. Catalytic abatement of nitrous oxide from nitric and production

    NARCIS (Netherlands)

    Oonk, J.

    1998-01-01

    Nitric acid production is identified as a main source of nitrous oxide. Options for emission reduction however are not available. TNO and Hydro Agri studied the technological and economic feasibility of catalytic decomposition of nitrous oxide in nitric acid tail-gases. Although in literature promis

  20. The role of nitric oxide in cancer

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Nitric oxide (NO) is a pleiotropic regulator, critical to numerous biological processes, including va-sodilatation, neurotransmission and macrophage-mediated immunity. The family of nitric oxide synthases(NOS) comprises inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS). Interest-ingly, various studies have shown that all three isoforms can be involved in promoting or inhibiting theetiology of cancer. NOS activity has been detected in tumour cells of various histogenetic origins and hasbeen associated with tumour grade, proliferation rate and expression of important signaling componentsassociated with cancer development such as the oestrogen receptor. It appears that high levels of NOSexpression (for example, generated by activated macrophages) may be cytostatic or cytotoxic for tumorcells, whereas low level activity can have the opposite effect and promote tumour growth. Paradoxicallytherefore, NO (and related reactive nitrogen species) may have both genotoxic and angiogenic properties.Increased NO-generation in a cell may select mutant p53 cells and contribute to tumour angiogenesis byupregulating VEGF. In addition, NO may modulate tumour DNA repair mechanisms by upregulating p53,poly(ADP-ribose) polymerase (PARP) and the DNA-dependent protein kinase (DNA-PK). An understand-ing at the molecular level of the role of NO in cancer will have profound therapeutic implications for thediagnosis and treatment of disease.

  1. Metastable Nitric Acid Trihydrate in Ice Clouds

    Science.gov (United States)

    Weiss, Fabian; Kubel, Frank; Gálvez, Oscar; Hölzel, Markus; Parker, Stewart F.; Baloh, Philipp; Iannarelli, Riccardo; Rossi, Michel J.; Grothe, Hinrich

    2016-04-01

    The composition of high altitude ice clouds is still a matter of intense discussion. The constituents in question are ice and nitric acid hydrates. The identification and formation mechanisms, however, are still unknown but are essential to understand atmospheric processing such as the seasonal ozone depletion in the lower polar stratosphere or the radiation balance of planet Earth. We found conclusive evidence for a long-predicted phase, which has been named alpha nitric acid trihydrate (alpha-NAT). This phase has been proven by combination of X-ray and neutron diffraction experiments allowing a convincing structure solution. Additionally, vibrational spectra (infrared and inelastic neutron scattering) were recorded and compared with theoretical calculations. A strong affinity between water ice and alpha-NAT has been found, which explains the experimental spectra and the phase transition kinetics essential for identification in the atmosphere. On the basis of our results, we propose a new three-step mechanism for NAT-formation in high altitude ice clouds. F. Weiss et al. Angew. Chem. Int. Ed. 2016, accepted, DOI:10.1002/anie.201510841

  2. Expired nitric oxide levels in adult asthmatics

    Directory of Open Access Journals (Sweden)

    Chiharu Okada

    1996-01-01

    Full Text Available The expired nitric oxide (NO concentration is known to be higher in asthmatic subjects than in normal subjects. To elucidate the role of NO in asthma, we examined the expired NO concentrations in relation to the type (atopic, mixed, non- atopic, and severity (mild, moderate, severe of asthmatics, as well as the influence of steroid treatment. Twenty-seven normal subjects, 48 asthmatics, 8 subjects with allergic rhinitis, and 13 subjects with pulmonary emphysema participated in the study. The expired NO concentration was significantly higher in asthmatics and patients with allergic rhinitis than in normal subjects (P<0.01. No significant difference was observed between the expired NO concentration in patients with pulmonary emphysema and that of normal subjects. The expired NO concentrations were significantly lower in non- atopic asthma than in atopic asthma. Nitric oxide levels were significantly lower in severe asthma than in mild asthma. High doses of steroid treatment are often used in severe asthma. The dose of inhaled beclomethasone and expired NO concentrations showed a negative correlation (r= −0.51587, P<0.004. Drip infusion of hydrocortisone tended to increase the exhaled NO concentration just after drip infusion, however, it decreased after 24 h. These results suggest that steroid treatment decreases the expired NO concentrations in asthmatics, although it cannot be concluded that NO increases the severity of asthma. The measurement of expired NO concentrations is an easy, non-invasive test, which may be a useful tool for monitoring the condition of asthmatics.

  3. Inhibition of calcifying nodule formation in cultured porcine aortic valve cells by nitric oxide donors.

    Science.gov (United States)

    Kennedy, Jennifer A; Hua, Xiang; Mishra, Kumaril; Murphy, Geraldine A; Rosenkranz, Anke C; Horowitz, John D

    2009-01-05

    Calcific aortic stenosis displays some similarities to atherosclerosis including evidence of endothelial dysfunction. Whether nitric oxide (NO), which is produced by valvular endothelium, has direct protective effects extending to calcification processes in aortic valve cells has not previously been examined. In vitro calcifying nodules in porcine aortic valve interstitial cell cultures, formed in response to transforming growth factor-beta1 (TGF-beta1) 5 ng/ml, were inhibited by NO donors DETA-NONOate 5-100 microM, and sodium nitroprusside (SNP) 3 microM. Raising intracellular cGMP concentrations, via 8-bromo cGMP 1 mM or via brain natiuretic peptide and C-type natiuretic peptide 0.1 microM, inhibited TGF-beta1-induced nodule formation, potentially implicating the cGMP pathway in the NO effect. Stimulation of interstitial cells with substance P or calcium ionophone (A23187) caused NO release and increased intracellular cGMP respectively. However in the presence of TGF-beta1 basal levels of NO production via nitric oxide synthase (NOS) were insufficient to affect nodule formation. Increased dihydroethidium (DHE) fluorescence in response to TGF-beta1, which was inhibited by DETA-NONOate and TEMPOL, suggested a role for intracellular superoxide in TGF-beta1 signalling. Moreover, nodule formation was suppressed by superoxide scavengers TEMPOL, hydralazine and polyethylene glycol-superoxide dismutase (PEG-SOD), but not SOD. In conclusion, NO donors, or agents raising intracellular cGMP levels, may protect aortic valve interstitial cells from early events leading to calcification.

  4. Biosynthesis of cardiac natriuretic peptides

    DEFF Research Database (Denmark)

    Goetze, Jens Peter

    2010-01-01

    . An inefficient post-translational prohormone maturation will also affect the biology of the cardiac natriuretic peptide system. This review aims at summarizing the myocardial synthesis of natriuretic peptides focusing on B-type natriuretic peptide, where new data has disclosed cardiac myocytes as highly...

  5. Expression Profiling of Genes Related to Endothelial Cells Biology in Patients with Type 2 Diabetes and Patients with Prediabetes

    Directory of Open Access Journals (Sweden)

    Sara Moradipoor

    2016-01-01

    Full Text Available Endothelial dysfunction appears to be an early sign indicating vascular damage and predicts the progression of atherosclerosis and cardiovascular disorders. Extensive clinical and experimental evidence suggests that endothelial dysfunction occurs in Type 2 Diabetes Mellitus (T2DM and prediabetes patients. This study was carried out with an aim to appraise the expression levels in the peripheral blood of 84 genes related to endothelial cells biology in patients with diagnosed T2DM or prediabetes, trying to identify new genes whose expression might be changed under these pathological conditions. The study covered a total of 45 participants. The participants were divided into three groups: group 1, patients with T2DM; group 2, patients with prediabetes; group 3, control group. The gene expression analysis was performed using the Endothelial Cell Biology RT2 Profiler PCR Array. In the case of T2DM, 59 genes were found to be upregulated, and four genes were observed to be downregulated. In prediabetes patients, increased expression was observed for 49 genes, with two downregulated genes observed. Our results indicate that diabetic and prediabetic conditions change the expression levels of genes related to endothelial cells biology and, consequently, may increase the risk for occurrence of endothelial dysfunction.

  6. Direct measurements of nitric oxide release in relation to expression of endothelial nitric oxide synthase in isolated porcine mitral valves

    DEFF Research Database (Denmark)

    Moesgaard, Sophia Gry; Olsen, Lisbeth Høier; Aasted, Bent;

    2007-01-01

    The aim of this study was to measure the direct release of nitric oxide (NO) from the porcine mitral valve using a NO microelectrode. Furthermore, the expression and localization of endothelial nitric oxide synthase (eNOS) in the mitral valve was studied using immunohistochemistry, Western blotting...

  7. Peptide vectors for gene delivery: from single peptides to multifunctional peptide nanocarriers.

    Science.gov (United States)

    Raad, Markus de; Teunissen, Erik A; Mastrobattista, Enrico

    2014-07-01

    The therapeutic use of nucleic acids relies on the availability of sophisticated delivery systems for targeted and intracellular delivery of these molecules. Such a gene delivery should possess essential characteristics to overcome several extracellular and intracellular barriers. Peptides offer an attractive platform for nonviral gene delivery, as several functional peptide classes exist capable of overcoming these barriers. However, none of these functional peptide classes contain all the essential characteristics required to overcome all of the barriers associated with successful gene delivery. Combining functional peptides into multifunctional peptide vectors will be pivotal for improving peptide-based gene delivery systems. By using combinatorial strategies and high-throughput screening, the identification of multifunctional peptide vectors will accelerate the optimization of peptide-based gene delivery systems.

  8. Biochemical functionalization of peptide nanotubes with phage displayed peptides

    Science.gov (United States)

    Swaminathan, Swathi; Cui, Yue

    2016-09-01

    The development of a general approach for the biochemical functionalization of peptide nanotubes (PNTs) could open up existing opportunities in both fundamental studies as well as a variety of applications. PNTs are spontaneously assembled organic nanostructures made from peptides. Phage display has emerged as a powerful approach for identifying selective peptide binding motifs. Here, we demonstrate for the first time the biochemical functionalization of PNTs via peptides identified from a phage display peptide library. The phage-displayed peptides are shown to recognize PNTs. These advances further allow for the development of bifunctional peptides for the capture of bacteria and the self-assembly of silver particles onto PNTs. We anticipate that these results could provide significant opportunities for using PNTs in both fundamental studies and practical applications, including sensors and biosensors nanoelectronics, energy storage devices, drug delivery, and tissue engineering.

  9. Localization of Brain Natriuretic Peptide Immunoreactivity in Rat Spinal Cord

    Directory of Open Access Journals (Sweden)

    Essam M Abdelalim

    2016-12-01

    Full Text Available Brain natriuretic peptide (BNP exerts its functions through natriuretic peptide receptors. Recently, BNP has been shown to be involved in a wide range of functions. Previous studies reported BNP expression in the sensory afferent fibers in the dorsal horn of the spinal cord. However, BNP expression and function in the neurons of the central nervous system are still controversial. Therefore, in this study, we investigated BNP expression in the rat spinal cord in detail using RT-PCR and immunohistochemistry. RT-PCR analysis showed that BNP mRNA was present in the spinal cord and DRG. BNP immunoreactivity was observed in different structures of the spinal cord, including the neuronal cell bodies and neuronal processes. BNP immunoreactivity was observed in the dorsal horn of the spinal cord and in the neurons of the intermediate column and ventral horn. Double-immunolabeling showed a high level of BNP expression in the afferent fibers (laminae I-II labeled with calcitonin gene-related peptide (CGRP, suggesting BNP involvement in sensory function. In addition, BNP was co-localized with CGRP and choline acetyltransferase in the motor neurons of the ventral horn. Together, these results indicate that BNP is expressed in sensory and motor systems of the spinal cord, suggesting its involvement in several biological actions on sensory and motor neurons via its binding to NPR-A and/or NPR-B in the DRG and spinal cord.

  10. Production of Nitric Oxide and Expression of Inducible Nitric Oxide Synthase in Ovarian Cystic Tumors

    Directory of Open Access Journals (Sweden)

    Rosekeila Simões Nomelini

    2008-01-01

    Full Text Available Tumor sections from nonneoplastic (n=15, benign (n=28, and malignant ovarian tumors (n=20 were obtained from 63 women. Immunohistochemistry of the tumor sections demonstrated that inducible nitric oxide synthase (iNOS expression was increased in ovarian cancer samples compared to nonneoplastic or benign tumor samples. Using the Griess method, nitric oxide (NO metabolite levels were also found to be elevated in malignant tumor samples compared to benign tumor samples (P80 μM were more frequent than NO levels <80 μM, and iNOS expression in well-differentiated carcinomas was greater than in moderately/poorly differentiated carcinomas (P<.05. These data suggest an important role for NO in ovarian carcinogenesis.

  11. Nitric oxide in liver fibrosis: The role of inducible nitric oxide synthase.

    Science.gov (United States)

    Iwakiri, Yasuko

    2015-12-01

    The inducible form of nitric oxide synthase (iNOS) is expressed in hepatic cells in pathological conditions. Its induction is involved in the development of liver fibrosis, and thus iNOS could be a therapeutic target for liver fibrosis. This review summarizes the role of iNOS in liver fibrosis, focusing on 1) iNOS biology, 2) iNOS-expressing liver cells, 3) iNOS-related therapeutic strategies, and 4) future directions.

  12. Regulation of adenosine triphosphate-sensitive potassium channels suppresses the toxic effects of amyloid-beta peptide (25-35)

    Institute of Scientific and Technical Information of China (English)

    Min Kong; Maowen Ba; Hui Liang; Peng Shao; Tianxia Yu; Ying Wang

    2013-01-01

    In this study, we treated PC12 cells with 0-20 μM amyloid-β peptide (25-35) for 24 hours to induce cytotoxicity, and found that 5-20 μM amyloid-β peptide (25-35) decreased PC12 cell viability, but adenosine triphosphate-sensitive potassium channel activator diazoxide suppressed the decrease reactive oxygen species levels. These protective effects were reversed by the selective mitochondrial adenosine triphosphate-sensitive potassium channel blocker 5-hydroxydecanoate. An inducible nitric oxide synthase inhibitor, Nω-nitro-L-arginine, also protected PC12 cells from intracellular reactive oxygen species levels. However, the H2O2-degrading enzyme catalase could that the increases in both mitochondrial membrane potential and reactive oxygen species levels adenosine triphosphate-sensitive potassium channels and nitric oxide. Regulation of adenosine triphosphate-sensitive potassium channels suppresses PC12 cell cytotoxicity induced by amyloid-β

  13. APD: the Antimicrobial Peptide Database.

    Science.gov (United States)

    Wang, Zhe; Wang, Guangshun

    2004-01-01

    An antimicrobial peptide database (APD) has been established based on an extensive literature search. It contains detailed information for 525 peptides (498 antibacterial, 155 antifungal, 28 antiviral and 18 antitumor). APD provides interactive interfaces for peptide query, prediction and design. It also provides statistical data for a select group of or all the peptides in the database. Peptide information can be searched using keywords such as peptide name, ID, length, net charge, hydrophobic percentage, key residue, unique sequence motif, structure and activity. APD is a useful tool for studying the structure-function relationship of antimicrobial peptides. The database can be accessed via a web-based browser at the URL: http://aps.unmc.edu/AP/main.html.

  14. Radiolabelled peptides for oncological diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Laverman, Peter; Boerman, Otto C.; Oyen, Wim J.G. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands); Sosabowski, Jane K. [Queen Mary University of London, Centre for Molecular Oncology, Barts Cancer Institute, London (United Kingdom)

    2012-02-15

    Radiolabelled receptor-binding peptides targeting receptors (over)expressed on tumour cells are widely under investigation for tumour diagnosis and therapy. The concept of using radiolabelled receptor-binding peptides to target receptor-expressing tissues in vivo has stimulated a large body of research in nuclear medicine. The {sup 111}In-labelled somatostatin analogue octreotide (OctreoScan trademark) is the most successful radiopeptide for tumour imaging, and was the first to be approved for diagnostic use. Based on the success of these studies, other receptor-targeting peptides such as cholecystokinin/gastrin analogues, glucagon-like peptide-1, bombesin (BN), chemokine receptor CXCR4 targeting peptides, and RGD peptides are currently under development or undergoing clinical trials. In this review, we discuss some of these peptides and their analogues, with regard to their potential for radionuclide imaging of tumours. (orig.)

  15. The role of nitric oxide in reproduction

    Directory of Open Access Journals (Sweden)

    McCann S.M.

    1999-01-01

    Full Text Available Nitric oxide (NO plays a crucial role in reproduction at every level in the organism. In the brain, it activates the release of luteinizing hormone-releasing hormone (LHRH. The axons of the LHRH neurons project to the mating centers in the brain stem and by afferent pathways evoke the lordosis reflex in female rats. In males, there is activation of NOergic terminals that release NO in the corpora cavernosa penis to induce erection by generation of cyclic guanosine monophosphate (cGMP. NO also activates the release of LHRH which reaches the pituitary and activates the release of gonadotropins by activating neural NO synthase (nNOS in the pituitary gland. In the gonad, NO plays an important role in inducing ovulation and in causing luteolysis, whereas in the reproductive tract, it relaxes uterine muscle via cGMP and constricts it via prostaglandins (PG.

  16. Hypoxia tolerance, nitric oxide, and nitrite

    DEFF Research Database (Denmark)

    Fago, Angela; Jensen, Frank Bo

    2015-01-01

    Among vertebrates able to tolerate periods of oxygen deprivation, the painted and red-eared slider turtles (Chrysemys picta and Trachemys scripta) and the crucian carp (Carassius carassius) are the most extreme and can survive even months of total lack of oxygen during winter. The key to hypoxia...... survival resides in concerted physiological responses, including strong metabolic depression, protection against oxidative damage and – in air breathing animals - redistribution of blood flow. Each of these responses is known to be tightly regulated by nitric oxide (NO) and during hypoxia by its metabolite...... nitrite. The aim of this review is to highlight recent work illustrating the widespread roles of NO and nitrite in the tolerance to extreme oxygen deprivation, in particular in the red-eared slider turtle and crucian carp, but also in diving marine mammals. The emerging picture underscores the importance...

  17. Nitric oxide-releasing porous silicon nanoparticles

    Science.gov (United States)

    Kafshgari, Morteza Hasanzadeh; Cavallaro, Alex; Delalat, Bahman; Harding, Frances J.; McInnes, Steven JP; Mäkilä, Ermei; Salonen, Jarno; Vasilev, Krasimir; Voelcker, Nicolas H.

    2014-07-01

    In this study, the ability of porous silicon nanoparticles (PSi NPs) to entrap and deliver nitric oxide (NO) as an effective antibacterial agent is tested against different Gram-positive and Gram-negative bacteria. NO was entrapped inside PSi NPs functionalized by means of the thermal hydrocarbonization (THC) process. Subsequent reduction of nitrite in the presence of d-glucose led to the production of large NO payloads without reducing the biocompatibility of the PSi NPs with mammalian cells. The resulting PSi NPs demonstrated sustained release of NO and showed remarkable antibacterial efficiency and anti-biofilm-forming properties. These results will set the stage to develop antimicrobial nanoparticle formulations for applications in chronic wound treatment.

  18. Nitric Oxide and Respiratory Helminthic Diseases

    Directory of Open Access Journals (Sweden)

    Antonio Muro

    2010-01-01

    Full Text Available Nitric oxide (NO is a very simple molecule that displays very important functions both in helminths (mainly those involved in respiratory pathology and in mammalian hosts. In this paper we review four issues related to interaction of NO and lung helminthic diseases. Firstly, we evaluated data available on the NO synthesis and release by helminths and their biological role. Next, we summarized the effect of antigens obtained from different phases of the biological cycle on NO production by host mammalian cells (mainly from human sources. Thirdly, we revised the evaluation of NO on the biological activities and/or the viability of respiratory helminths. Lastly, the deleterious consequences of increased production of NO during helminthic human infection are detailed.

  19. Melatonin and its precursors scavenge nitric oxide

    Energy Technology Data Exchange (ETDEWEB)

    Noda, Y.; Mori, A.; Liburdy, R.; Packer, L.

    1998-12-01

    Nitric oxide (NO) scavenging activity of melatonin, N-acetyl-5-hydroxytryptamine, serotonin, 5-hydroxytryptophan and L-tryptophan was examined by the Griess reaction using flow injection analysis. 1-Hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene(NOC-7) was used as NO generator. The Griess reagent stoichiometrically reacts with NO2-, which was converted by a cadmium-copper reduction column from the stable end products of NO oxidation. Except for tryptophan, all the compounds examined scavenged NO in a dose-dependent manner. Melatonin, which has a methoxy group in the 5-position and an acetyl side chain, exhibited the most potent scavenging activity among the compounds tested. Serotonin, N-acetyl-5-hydroxytryptamine, and 5-hydroxytryptophan, respectively, showed moderate scavenging activity compared to melatonin. Tryptophan, which has neither a methoxy nor a hydroxyl group in the 5-position, exhibited the least NO scavenging activity.

  20. Nitric Oxide Synthase Inhibitors as Antidepressants

    Directory of Open Access Journals (Sweden)

    Vallo Volke

    2010-01-01

    Full Text Available Affective and anxiety disorders are widely distributed disorders with severe social and economic effects. Evidence is emphatic that effective treatment helps to restore function and quality of life. Due to the action of most modern antidepressant drugs, serotonergic mechanisms have traditionally been suggested to play major roles in the pathophysiology of mood and stress-related disorders. However, a few clinical and several pre-clinical studies, strongly suggest involvement of the nitric oxide (NO signaling pathway in these disorders. Moreover, several of the conventional neurotransmitters, including serotonin, glutamate and GABA, are intimately regulated by NO, and distinct classes of antidepressants have been found to modulate the hippocampal NO level in vivo. The NO system is therefore a potential target for antidepressant and anxiolytic drug action in acute therapy as well as in prophylaxis. This paper reviews the effect of drugs modulating NO synthesis in anxiety and depression.

  1. Citric Acid Alternative to Nitric Acid Passivation

    Science.gov (United States)

    Lewis, Pattie L. (Compiler)

    2013-01-01

    The Ground Systems Development and Operations GSDO) Program at NASA John F. Kennedy Space Center (KSC) has the primary objective of modernizing and transforming the launch and range complex at KSC to benefit current and future NASA programs along with other emerging users. Described as the launch support and infrastructure modernization program in the NASA Authorization Act of 2010, the GSDO Program will develop and implement shared infrastructure and process improvements to provide more flexible, affordable, and responsive capabilities to a multi-user community. In support of the GSDO Program, the purpose of this project is to demonstratevalidate citric acid as a passivation agent for stainless steel. Successful completion of this project will result in citric acid being qualified for use as an environmentally preferable alternative to nitric acid for passivation of stainless steel alloys in NASA and DoD applications.

  2. The nitric oxide synthase of mouse spermatozoa.

    Science.gov (United States)

    Herrero, M B; Goin, J C; Boquet, M; Canteros, M G; Franchi, A M; Perez Martinez, S; Polak, J M; Viggiano, J M; Gimeno, M A

    1997-07-01

    Nitric oxide synthase (NOS) was evidenced in mature mouse spermatozoa by means of biochemical techniques and Western blot. During 120 min of incubation, 10(7) spermatozoa synthesized 7 +/- 2 pmol of L-[14C]citrulline. Besides, L-citrulline formation depended on the incubation time and on the concentration of L-arginine present in the incubation medium. Different concentrations of N(G)-nitro-L-arginine methyl ester (L-NAME) but not aminoguanidine, inhibited L-[14C]citrulline formation. Western-blot analysis of solubilized sperm proteins revealed a unique band of M(r)=140 kDa with the neural, endothelial and inducible NOS antisera tested. These results provide evidence that mature mouse sperm contains a NOS isoform and that spermatozoa have the potential ability to synthesize NO, suggesting a role for endogenous NO on mammalian sperm function.

  3. Nitric oxide turnover in permeable river sediment

    DEFF Research Database (Denmark)

    Schreiber, Frank; Stief, Peter; Kuypers, Marcel M M;

    2014-01-01

    We measured nitric oxide (NO) microprofiles in relation to oxygen (O2) and all major dissolved N-species (ammonium, nitrate, nitrite, and nitrous oxide [N2O]) in a permeable, freshwater sediment (River Weser, Germany). NO reaches peak concentrations of 0.13 μmol L-1 in the oxic zone and is consumed...... in the oxic-anoxic transition zone. Apparently, NO is produced by ammonia oxidizers under oxic conditions and consumed by denitrification under microoxic conditions. Experimental percolation of sediment cores with aerated surface water resulted in an initial rate of NO production that was 12 times higher than...... the net NO production rate in steady state. This initial NO production rate is in the same range as the net ammonia oxidation rate, indicating that NO is transiently the main product of ammonia oxidizers. Stable isotope labeling experiments with the 15N-labeled chemical NO donor S...

  4. Hypoxia tolerance, nitric oxide, and nitrite

    DEFF Research Database (Denmark)

    Fago, Angela; Jensen, Frank Bo

    2015-01-01

    Among vertebrates able to tolerate periods of oxygen deprivation, the painted and red-eared slider turtles (Chrysemys picta and Trachemys scripta) and the crucian carp (Carassius carassius) are the most extreme and can survive even months of total lack of oxygen during winter. The key to hypoxia ...... of NO and nitrite signaling in the adaptive response to hypoxia in vertebrate animals....... survival resides in concerted physiological responses, including strong metabolic depression, protection against oxidative damage and – in air breathing animals - redistribution of blood flow. Each of these responses is known to be tightly regulated by nitric oxide (NO) and during hypoxia by its metabolite...... nitrite. The aim of this review is to highlight recent work illustrating the widespread roles of NO and nitrite in the tolerance to extreme oxygen deprivation, in particular in the red-eared slider turtle and crucian carp, but also in diving marine mammals. The emerging picture underscores the importance...

  5. Unordered structured of proinsulin C-peptide in aqueous solution and in the presence of lipid vesicles.

    Science.gov (United States)

    Henriksson, M; Shafqat, J; Liepinsh, E; Tally, M; Wahren, J; Jörnvall, H; Johansson, J

    2000-02-01

    Proinsulin C-peptide ameliorates renal and autonomic nerve function and increases skeletal muscle blood flow, oxygen uptake and glucose transport in patients with insulin-dependent diabetes mellitus. These effects have in part been ascribed to the stimulatory influence of C-peptide on Na+,K+-ATPase and endothelial nitric oxide synthase. To evaluate the capacity of C-peptide to insert into lipid bilayers and form ion channels, C-peptide secondary structure and membrane interactions were studied with circular dichroism spectroscopy and size exclusion chromatography. C-peptide is shown to lack a stable secondary structure, both when part of proinsulin and when free in aqueous solution, although the N-terminal third of the peptide exhibits an alpha-helical conformation in trifluoroethanol. Moreover, C-peptide remains disordered in the aqueous solvent in the presence of lipid vesicles, regardless of vesicle composition. In conclusion, C-peptide is unlikely to elicit physiological effects through stable conformation-dependent interactions with lipid membranes.

  6. Autotrophic Biofilters for Oxidation of Nitric Oxide

    Institute of Scientific and Technical Information of China (English)

    陈建孟; 陈浚; LanceHershman; 王家德; DanielP.Y.Chang

    2004-01-01

    Carbon foam—a kind of new engineering material as packing material was adopted in three biofilters with different pore dimensions and adapted autotrophic nitrite nitrobacteria to investigate the purification of nitric oxide (NO) in a gas stream. The biofilm was developed on the surface of carbon foams using nitrite as its only nitric source. The moisture in the filter was maintained by ultrasonic aerosol equipment which can minimize the thickness of the liquid film. The liquid phase nitrification test was conducted to determine the variability and the potential of performance among the three carbon foam biofilters. The investigation showed that during the NO2-—N inlet concentration of 200 g·L-1·min-1 to 800 g·L-1·min-1, the 24PPC (pores per centimeter) carbon foam biofilter had the greatest potential, achieving the NO2-—N removal efficiency of 94% to 98%. The 8PPC and 18PPC carbon foam biofilters achieved the NO2-—N removal efficiency of 15% to 21% and of 30% to 40%, respectively. The potential for this system to remove NO from a gas stream was shown on the basis of a steady removal efficiency of 41% to 50% which was attained for the 24PPC carbon foam biofilter at specified NO inlet concentration of 66.97 mg·m-3 to 267.86mg·m-3 and an empty-bed residence time of 3.5 min.

  7. Nitric oxide in the psychobiology of mental disorders

    Directory of Open Access Journals (Sweden)

    Altan Eşsizoğlu

    2009-03-01

    Full Text Available Nitric oxide is in a gaseous form and is widespread in the human body. It functions by acting as a secondary messenger in the modulatory activities of neuronal functions of the central nervous system. Nitric oxide is the first identified neurotransmitter of the nontraditional neurotransmitter family.Studies conducted on experimental animals demonstrate that nitric oxide has a neuromodulatory efficacy on the secretions of other neurotransmitters and that it has an effect on learning and memory functions, and on various neuronal mechanisms. Many studies have been conducted to investigate the location of nitric oxide in the central nervous system, its effect on anxiety and depression, its relationship with other neurotransmitters, and also about its role on neurotoxicity. There are clinical studies concerning the level of nitrate, a product of nitric oxide metabolism, and also experimental studies concerning its rewarding effect of alcohol and substance use, in patients with depression and schizophrenia. However, limited studies have been conducted to investigate its relationship with stress, which is an important factor in the etiology of psychiatric disorders. These studies demonstrate that nitric oxide is closely related with stress physiology.Nitric oxide is a neuromodulator, which is frequently being mentioned about nowadays in psychiatry. Clinical and experimental studies play an important role in the psychobiology of psychiatric disorders.

  8. Corrosion studies in fuel element reprocessing environments containing nitric acid

    Energy Technology Data Exchange (ETDEWEB)

    Beavers, J A; White, R R; Berry, W E; Griess, J C

    1982-04-01

    Nitric acid is universally used in aqueous fuel element reprocessing plants; however, in the processing scheme being developed by the Consolidated Fuel Reprocessing Program, some of the equipment will be exposed to nitric acid under conditions not previously encountered in fuel element reprocessing plants. A previous report presented corrosion data obtained in hyperazeotropic nitric acid and in concentrated magnesium nitrate solutions used in its preparation. The results presented in this report are concerned with the following: (1) corrosion of titanium in nitric acid; (2) corrosion of nickel-base alloys in a nitric acid-hydrofluoric acid solution; (3) the formation of Cr(VI), which enhances corrosion, in nitric acid solutions; and (4) corrosion of mechanical pipe connectors in nitric acid. The results show that the corrosion rate of titanium increased with the refreshment rate of boiling nitric acid, but the effect diminished rapidly as the temperature decreased. The addition of iodic acid inhibited attack. Also, up to 200 ppM of fluoride in 70% HNO/sub 3/ had no major effect on the corrosion of either titanium or tantalum. In boiling 8 M HNO/sub 3/-0.05 M HF, Inconel 671 was more resistant than Inconel 690, but both alloys experienced end-grain attack. In the case of Inconel 671, heat treatment was very important; annealed and quenched material was much more resistant than furnace-cooled material.The rate of oxidation of Cr(III) to Cr(VI) increased significantly as the nitric acid concentration increased, and certain forms of ruthenium in the solution seemed to accelerate the rate of formation. Mechanical connectors of T-304L stainless steel experienced end-grain attack on the exposed pipe ends, and seal rings of both stainless steel and a titanium alloy (6% Al-4% V) underwent heavy attack in boiling 8 M HNO/sub 3/.

  9. Avian host defense peptides.

    Science.gov (United States)

    Cuperus, Tryntsje; Coorens, Maarten; van Dijk, Albert; Haagsman, Henk P

    2013-11-01

    Host defense peptides (HDPs) are important effector molecules of the innate immune system of vertebrates. These antimicrobial peptides are also present in invertebrates, plants and fungi. HDPs display broad-spectrum antimicrobial activities and fulfill an important role in the first line of defense of many organisms. It is becoming increasingly clear that in the animal kingdom the functions of HDPs are not confined to direct antimicrobial actions. Research in mammals has indicated that HDPs have many immunomodulatory functions and are also involved in other physiological processes ranging from development to wound healing. During the past five years our knowledge about avian HDPs has increased considerably. This review addresses our current knowledge on the evolution, regulation and biological functions of HDPs of birds.

  10. Antimicrobial peptides in Echinoderms

    Directory of Open Access Journals (Sweden)

    C Li

    2010-05-01

    Full Text Available Antimicrobial peptides (AMPs are important immune effector molecules for invertebrates, including echinoderms, which lack a vertebrate-type adaptive immune system. Here we summarize the knowledge of such peptides in echinoderms. Strongylocins are a novel family of cysteine-rich AMPs, recently identified in the sea urchins, Strongylocentrotus droebachiensis and S. purpuratus. Although these molecules present diverse amino acid sequences, they share an identical cysteine arrangement pattern, dissimilar to other known AMPs. A family of heterodimeric AMPs, named centrocins, are also present in S. droebachiensis. Lysozymes and fragments of larger proteins, such as beta-thymocins, actin, histone 2A and filamin A have also been shown to display antimicrobial activities in echinoderms. Future studies on AMPs should be aimed in revealing how echinoderms use these AMPs in the immune response against microbial pathogens.

  11. Antimicrobial Peptides (AMPs

    Directory of Open Access Journals (Sweden)

    Mehrzad Sadredinamin

    2016-04-01

    Full Text Available Antimicrobial peptides (AMPs are extensive group of molecules that produced by variety tissues of invertebrate, plants, and animal species which play an important role in their immunity response. AMPs have different classifications such as; biosynthetic machines, biological sources, biological functions, molecular properties, covalent bonding patterns, three dimensional structures, and molecular targets.These molecules have multidimensional properties including antimicrobial activity, antiviral activity, antifungal activity, anti-parasite activity, biofilm control, antitumor activity, mitogens activity and linking innate to adaptive immunity that making them promising agents for therapeutic drugs. In spite of this advantage of AMPs, their clinical developments have some limitation for commercial development. But some of AMPs are under clinical trials for the therapeutic purpose such as diabetic foot ulcers, different bacterial infections and tissue damage. In this review, we emphasized on the source, structure, multidimensional properties, limitation and therapeutic applications of various antimicrobial peptides.

  12. Mitochondrial N-formyl peptides cause airway contraction and lung neutrophil infiltration via formyl peptide receptor activation.

    Science.gov (United States)

    Wenceslau, Camilla Ferreira; Szasz, Theodora; McCarthy, Cameron G; Baban, Babak; NeSmith, Elizabeth; Webb, R Clinton

    2016-04-01

    Respiratory failure is a common characteristic of systemic inflammatory response syndrome (SIRS) and sepsis. Trauma and severe blood loss cause the release of endogenous molecules known as damage-associated molecular patterns (DAMPs). Mitochondrial N-formyl peptides (F-MITs) are DAMPs that share similarities with bacterial N-formylated peptides, and are potent immune system activators. Recently, we observed that hemorrhagic shock-induced increases in plasma levels of F-MITs associated with lung damage, and that antagonism of formyl peptide receptors (FPR) ameliorated hemorrhagic shock-induced lung injury in rats. Corroborating these data, in the present study, it was observed that F-MITs expression is higher in plasma samples from trauma patients with SIRS or sepsis when compared to control trauma group. Therefore, to better understand the role of F-MITs in the regulation of lung and airway function, we studied the hypothesis that F-MITs lead to airway contraction and lung inflammation. We observed that F-MITs induced concentration-dependent contraction in trachea, bronchi and bronchioles. However, pre-treatment with mast cells degranulator or FPR antagonist decreased this response. Finally, intratracheal challenge with F-MITs increased neutrophil elastase expression in lung and inducible nitric oxide synthase and cell division control protein 42 expression in all airway segments. These data suggest that F-MITs could be a putative target to treat respiratory failure in trauma patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Peptides and Food Intake

    OpenAIRE

    Carmen Sobrino Crespo; Aranzazu Perianes Cachero; Lilian Puebla Jiménez; Vicente eBarrios; Eduardo eArilla

    2014-01-01

    The mechanisms for controlling food intake involve mainly an interplay between gut, brain, and adipose tissue (AT), among the major organs. Parasympathetic, sympathetic, and other systems are required for communication between the brain satiety center, gut, and AT. These neuronal circuits include a variety of peptides and hormones, being ghrelin the only orexigenic molecule known, whereas the plethora of other factors are inhibitors of appetite, suggesting its physiological relevance in the r...

  14. Adverse experiences with nitric acid at the Savannah River Site

    Energy Technology Data Exchange (ETDEWEB)

    Durant, W.S.; Craig, D.K.; Vitacco, M.J.; McCormick, J.A.

    1991-06-01

    Nitric acid is used routinely at the Savannah River Site (SRS) in many processes. However, the site has experienced a number of adverse situations in handling nitric acid. These have ranged from minor injuries to personnel to significant explosions. This document compiles many of these events and includes discussions of process upsets, fires, injuries, and toxic effects of nitric acid and its decomposition products. The purpose of the publication is to apprise those using the acid that it is a potentially dangerous material and can react in many ways as demonstrated by SRS experience. 10 refs.

  15. Association of Variants in Genes Related to the Immune Response and Obesity with Benign Prostatic Hyperplasia in CLUE II

    Science.gov (United States)

    Lopez, David S.; Peskoe, Sarah B.; Tsilidis, Konstantinos K.; Hoffman-Bolton, Judy; Helzlsouer, Kathy J.; Isaacs, William B.; Smith, Michael W.; Platz, Elizabeth A.

    2014-01-01

    BACKGROUND Chronic inflammation and obesity may contribute to the genesis or progression of benign prostatic hyperplasia (BPH) and BPH-associated lower urinary tract symptoms (LUTS). The influence of variants in genes related to these states on BPH has not been studied extensively. Thus, we evaluated the association of 17 single nucleotide polymorphisms (SNPs) in immune response genes (IL1B, IL6, IL8, IL10, TNF, CRP, TLR4, RNASEL) and genes involved in obesity, including insulin regulation (LEP, ADIPOQ, PPARG, TCF7L2), with BPH. METHODS BPH cases (N=568) and age-frequency matched controls (N=568) were selected from among adult male CLUE II cohort participants who responded in 2000 to a mailed questionnaire. BPH was defined as BPH surgery, use of BPH medications, or symptomatic BPH (American Urological Association Symptom Index Score ≥15). Controls were men who had not had BPH surgery, did not use BPH medications, and whose symptom score was ≤7. Age-adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. RESULTS None of the candidate SNPs was statistically significantly associated with BPH. However, we could not rule out possible weak associations for CRP rs1205 (1082C>T), ADIPOQ rs1501299 (276C>A), PPARG rs1801282 (-49C>G), and TCF7L2 rs7903146 (47833T>C). After summing risk alleles, men with ≥4 had an increased BPH risk compared with those with ≤1 (OR, 1.78; 95% CI, 1.10-2.89; Ptrend=0.006). CONCLUSION SNPs in genes related to immune response and obesity, especially in combination, may be associated with BPH. PMID:25224558

  16. Association of common polymorphisms in IL10, and in other genes related to inflammatory response and obesity with colorectal cancer

    Science.gov (United States)

    Tsilidis, Konstantinos K.; Helzlsouer, Kathy J.; Smith, Michael W.; Grinberg, Victoriya; Hoffman-Bolton, Judith; Clipp, Sandra L.; Visvanathan, Kala

    2011-01-01

    Objective and methods The association of 17 candidate single nucleotide polymorphisms (SNPs) in IL10 and other immune response genes (CRP, TLR4, IL6, IL1B, IL8, TNF, RNASEL) and genes related to obesity (PPARG, TCF7L2, ADIPOQ, LEP) with colorectal cancer was investigated. Haplotype tagging SNPs were chosen for IL10, CRP, and TLR4. Incident colorectal cancer cases (n = 208) and matched controls (n = 381) were identified between baseline in 1989 and 2003 among participants in the CLUE II cohort. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using conditional logistic regression. Results Compared with the AA genotype at the candidate IL10-1082 locus (rs1800896), carrying one (OR, 0.79; 95% CI, 0.53–1.18) or two (OR, 0.58; 95% CI, 0.35–0.95) G alleles, a known higher producer of the anti-inflammatory cytokine IL-10, was associated with lower risk of colorectal cancer (ptrend = 0.03). Statistically significant associations with colorectal cancer were observed for three tagSNPs in IL10 (rs1800890, rs3024496, rs3024498) and one common haplotype, but these associations were due to high linkage disequilibrium with IL10-1082. Two CRP haplotypes (global p = 0.04) and TLR4 tagSNPs (rs7873784, rs11536891), but not TLR4 haplotypes, were associated with colorectal cancer. Conclusions Our study suggests that polymorphisms in IL10, and also possibly in CRP and other genes related to immune response or obesity may be associated with colorectal cancer. PMID:19760027

  17. [C-peptide physiological effects].

    Science.gov (United States)

    Shpakov, A O; Granstrem, O K

    2013-02-01

    In the recent years there were numerous evidences that C-peptide, which was previously considered as a product of insulin biosynthesis, is one of the key regulators of physiological processes. C-peptide via heterotrimeric G(i/o) protein-coupled receptors activates a wide range of intracellular effector proteins and transcription factors and, thus, controls the inflammatory and neurotrophic processes, pain sensitivity, cognitive function, macro- and microcirculation, glomerular filtration. These effects of C-peptide are mainly expressed in its absolute or relative deficiency occurred in type 1 diabetes mellitus and they are less pronounced when the level of C-peptide is close to normal. Replacement therapy with C-peptide prevents many complications of type 1 diabetes, such as atherosclerosis, diabetic peripheral neuropathy, and nephropathy. C-peptide interacts with the insulin hexamer complexes and induces their dissociation and, as a result, regulates the functional activity of the insulin signaling system. At the same time, C-peptide at the concentrations above physiological may demonstrate pro-inflammatory effects on the endothelial cells and cause atherosclerotic changes in the vessels, which should be considered in the study of pathogenic mechanisms of complications of type 2 diabetes mellitus, where the level of C peptide is increased, as well as in the development of approaches for C-peptide application in clinic. This review is devoted contemporary achievements and unsolved problems in the study of C-peptide, as an important regulator of physiological and biochemical processes.

  18. Nitric acid vapor removal by activated, impregnated carbons

    Energy Technology Data Exchange (ETDEWEB)

    Wood, G.O.

    1996-12-31

    Laboratory and industrial workers can be exposed to vapors of nitric acid, especially in accidents, such as spills. Nitric acid can also be a product of incineration for energy production or waste (e.g., CW agent) disposal. Activated carbons containing impregnants for enhancing vapor and gas removal have been tested for effectiveness in removing vapors of nitric acid from air. The nitric acid vapor was generated from concentrated acid solutions and detected by trapping in a water bubbler for pH measurements. Both low and moderate relative humidity conditions were used. All carbons were effective at vapor contact times representative of air-purifying respirator use. One surprising observation was the desorption of low levels of ammonia from impregnated carbons. This was apparently due to residual ammonia from the impregnation processes.

  19. Nitric oxide metabolites in goldfish under normoxic and hypoxic conditions

    DEFF Research Database (Denmark)

    Hansen, Marie N.; Jensen, Frank Bo

    2010-01-01

    Nitric oxide (NO), produced by nitric oxide synthases (NOS enzymes), regulates multiple physiological functions in animals. NO exerts its effects by binding to iron (Fe) of heme groups (exemplified by the activation of soluble guanylyl cyclase) and by S-nitrosylation of proteins – and it is metab......Nitric oxide (NO), produced by nitric oxide synthases (NOS enzymes), regulates multiple physiological functions in animals. NO exerts its effects by binding to iron (Fe) of heme groups (exemplified by the activation of soluble guanylyl cyclase) and by S-nitrosylation of proteins...... levels was assessed from metabolic and respiratory variables. In normoxic goldfish, the concentrations of NO metabolites in plasma and tissues were comparable with values reported in mammals, indicative of similar NOS activity. Exposure to hypoxia [at PO2 (partial pressure of O2) values close...

  20. Inducible nitric oxide synthase mediates bone loss in ovariectomized mice.

    NARCIS (Netherlands)

    Cuzzocrea, S.; Mazzon, E.; Dugo, L.; Genovese, T.; Paola, R. Di; Ruggeri, Z.; Vegeto, E.; Caputi, A.P.; Loo, F.A.J. van de; Puzzolo, D.; Maggi, A.

    2003-01-01

    Several clinical studies have shown that bone loss may be attributed to osteoclast recruitment induced by mediators of inflammation. In different experimental paradigms we have recently demonstrated that estrogen exhibits antiinflammatory activity by preventing the induction of inducible nitric

  1. The Effect of Nitric Oxide Donor in Diabetic Wound Healing

    Directory of Open Access Journals (Sweden)

    N Dashti

    2003-10-01

    Full Text Available Diabetes is characterized by a nitric oxide deficiency at the wound site. Diabetes is a factor that influences all stages of wound healing. In animals with acute experimental diabetes induced by streptozotocin (STZ, the early inflammatory responses after wounding is impaired, fibroblast and endothelial cell proliferation is reduced as well as accumulation of reparative collagen and gain in wound breaking strenght. This study investigated whether exogenous nitric oxide supplimentation with nitric oxide donor DETA NONOate could reverse impaired healing in diabetes. The results suggest nitric oxide donor DETA NONOate can reverse impaired healing associated with diabetes (P<0.001 and urinary nitrate (NO-3 output may reflect the extent of repair in this wound model (P<0.001.

  2. Inducible nitric oxide synthase mediates bone loss in ovariectomized mice.

    NARCIS (Netherlands)

    Cuzzocrea, S.; Mazzon, E.; Dugo, L.; Genovese, T.; Paola, R. Di; Ruggeri, Z.; Vegeto, E.; Caputi, A.P.; Loo, F.A.J. van de; Puzzolo, D.; Maggi, A.

    2003-01-01

    Several clinical studies have shown that bone loss may be attributed to osteoclast recruitment induced by mediators of inflammation. In different experimental paradigms we have recently demonstrated that estrogen exhibits antiinflammatory activity by preventing the induction of inducible nitric oxid

  3. Adhesion Development and the Expression of Endothelial Nitric Oxide Synthase

    Directory of Open Access Journals (Sweden)

    David M. Svinarich

    2001-01-01

    Full Text Available Objective: This study was conducted to determine whether nitric oxide (NO, a potent vasodilator and inhibitor of thrombus formation, is involved in the formation and maintenance of adhesions.

  4. Serum nitric oxide and homocysteine as biomarkers of ectopic pregnancy

    Directory of Open Access Journals (Sweden)

    Kavitha Meiyappan

    2015-02-01

    Full Text Available Background: Aim of current study was to evaluate the role of serum homocysteine and nitric oxide in the diagnosis of ectopic pregnancy. Methods: The study included 32 patients with ruptured ectopic, 29 miscarriage patients and 30 normal pregnant women as controls. Fasting plasma homocysteine, serum folate, vitamin B12 levels and nitric oxide levels were estimated at the time of admission. Results: Plasma homocysteine levels were significantly lower in patients with ectopic pregnancy than normal pregnancy. Nitric oxide levels were significantly lower in patients with abortion. Conclusions: Patients with abortion have decreased circulating nitric oxide levels in serum while those with ectopic pregnancies have decreased homocysteine levels. [Int J Reprod Contracept Obstet Gynecol 2015; 4(1.000: 66-70

  5. Nitric oxide damages neuronal mitochondria and induces apoptosis in neurons

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The cytotoxic effect of nitric oxide on primarily cultured rat cerebellar granule cells was studied,and the mechanisms were discussed.The results showed that nitric oxide donor S-nitroso-N-acetyl-penicillamine (SNAP; 500 μmol/L) could induce apoptosis in immature cultures of cerebellar granule cells.Flow cytometry and HPLC analyses revealed that after treatment with SNAP,the mitochondrial transmembrane potential and the cellular ATP content decreased significantly.Nitric oxide scavenger hemoglobin could effectively prevent the neuronal mitochondria from dysfunction and attenuate apoptosis.The results suggested that nitric oxide activated the apoptotic program by inhibiting the activity of mitochondrial respiratory chain and thus decreasing the cellular ATP content.

  6. Nitric oxide synthase and nitric oxide alterations in chronically stressed rats: a model for nitric oxide in major depressive disorder.

    Science.gov (United States)

    Gao, Shang-Feng; Lu, Yun-Rong; Shi, Li-Gen; Wu, Xue-Yan; Sun, Bo; Fu, Xin-Yan; Luo, Jian-Hong; Bao, Ai-Min

    2014-09-01

    Nitric oxide (NO) and NO synthase-1 (NOS1) are involved in the stress response and in depression. We compared NOS-NO alterations in rats exposed to chronic unpredictable stress (CUS) with alterations in major depressive disorder (MDD) in humans. In the hypothalamus of male CUS rats we determined NOS activity, and in the paraventricular nucleus (PVN) we determined NOS1-immunoreactive (ir) cell densities and co-localization of NOS1 with stress-related neuropeptides corticotropin-releasing hormone (CRH), vasopressin (AVP) or oxytocin (OXT). We measured plasma NO levels and cortisol in male medicine-naïve MDD patients and plasma NO and corticosterone (CORT) in CUS rats. In the CUS rat total NOS activity in the hypothalamus (P=0.018) and NOS1-ir cell density in the PVN were both significantly decreased (P=0.018), while NOS1 staining was mainly expressed in OXT-ir neurons in this nucleus. Interestingly, plasma NO levels were significantly increased both in male CUS rats (P=0.001) and in male MDD patients (Pdepression.

  7. Macrophage colony-stimulating factor augments beta-amyloid-induced interleukin-1, interleukin-6, and nitric oxide production by microglial cells.

    Science.gov (United States)

    Murphy, G M; Yang, L; Cordell, B

    1998-08-14

    In Alzheimer's disease (AD), a chronic cerebral inflammatory state is thought to lead to neuronal injury. Microglia, intrinsic cerebral immune effector cells, are likely to be key in the pathophysiology of this inflammatory state. We showed that macrophage colony-stimulating factor, a microglial activator found at increased levels in the central nervous system in AD, dramatically augments beta-amyloid peptide (betaAP)-induced microglial production of interleukin-1, interleukin-6, and nitric oxide. In contrast, granulocyte macrophage colony-stimulating factor, another hematopoietic cytokine found in the AD brain, did not augment betaAP-induced microglial secretory activity. These results indicate that increased macrophage colony-stimulating factor levels in AD could magnify betaAP-induced microglial inflammatory cytokine and nitric oxide production, which in turn could intensify the cerebral inflammatory state by activating astrocytes and additional microglia, as well as directly injuring neurons.

  8. Potassium softens vascular endothelium and increases nitric oxide release

    OpenAIRE

    2009-01-01

    In the presence of aldosterone, plasma sodium in the high physiological range stiffens endothelial cells and reduces the release of nitric oxide. We now demonstrate effects of extracellular potassium on stiffness of individual cultured bovine aortic endothelial cells by using the tip of an atomic force microscope as a mechanical nanosensor. An acute increase of potassium in the physiological range swells and softens the endothelial cell and increases the release of nitric oxide. A high physio...

  9. Serum nitric oxide and homocysteine as biomarkers of ectopic pregnancy

    OpenAIRE

    Kavitha Meiyappan; Pooja Dhiman; Soundravally Rajendiren; Krishnalatha Thayagarajan; Soundara Raghavan S

    2015-01-01

    Background: Aim of current study was to evaluate the role of serum homocysteine and nitric oxide in the diagnosis of ectopic pregnancy. Methods: The study included 32 patients with ruptured ectopic, 29 miscarriage patients and 30 normal pregnant women as controls. Fasting plasma homocysteine, serum folate, vitamin B12 levels and nitric oxide levels were estimated at the time of admission. Results: Plasma homocysteine levels were significantly lower in patients with ectopic pregnancy t...

  10. Diamagnetism and Strucure of Nitric Acid-Treated Bulk Polyethylene

    OpenAIRE

    Ania, F.; Baltá Calleja, F. J.; Cagiao, M.E.

    1982-01-01

    An alternative procedure to examine the nature of the end product of nitric-acid-treated bulk polyethylene involving the measurement of the diamagnetic susceptibility is reported. This simple non-destructive method complements previous results obtained by means of IR spectroscopy. Thus after selectively removing the surface layer of the polyethylene lamellae with nitric acid (t > 50h) the diamagnetic susceptibility substantially decreases to values wich are consistent with tilted paraff...

  11. Acute chemical pneumonitis caused by nitric acid inhalation: case report

    Energy Technology Data Exchange (ETDEWEB)

    Choe, Hyung Shim; Lee, In Jae; Ko, Eun Young; Lee, Jae Young; Kim, Hyun Beom; Hwang, Dae Hyun; Lee, Kwan Seop; Lee, Yul; Bae, Sang Hoon [Hallym University Sacred Heart Hospital, Anyang (Korea, Republic of)

    2003-06-01

    Chemical pneumonitis induced by nitric acid inhalation is a rare clinical condition. The previously reported radiologic findings of this disease include acute permeability pulmonary edema, delayed bronchiolitis obliterans, and bronchiectasis. In very few published rare radiologic reports has this disease manifested as acute alveolar injury; we report a case of acute chemical pneumonitis induced by nitric acid inhalation which at radiography manifested as bilateral perihilar consolidation and ground-glass attenuation, suggesting acute alveolar injury.

  12. Structural Characterization of Peptide Antibodies

    DEFF Research Database (Denmark)

    Chailyan, Anna; Marcatili, Paolo

    2015-01-01

    The role of proteins as very effective immunogens for the generation of antibodies is indisputable. Nevertheless, cases in which protein usage for antibody production is not feasible or convenient compelled the creation of a powerful alternative consisting of synthetic peptides. Synthetic peptides...... can be modified to obtain desired properties or conformation, tagged for purification, isotopically labeled for protein quantitation or conjugated to immunogens for antibody production. The antibodies that bind to these peptides represent an invaluable tool for biological research and discovery...

  13. NITRIC OXIDE SYNTHESIS IN MYOCARDIUM FOLLOWING BURN INJURY IN RATS

    Institute of Scientific and Technical Information of China (English)

    王卫东; 陈宗荣; 李蓉; 楼淑芳

    1998-01-01

    The nitric oxide and cyclic GMP production in myocardium early after burn injury in tats were investigated. Nitric oxide synthase activity was measured in cytosols from the left ventricular wall of burned rats.Cytosols from the control group animals were shown to contain mainly Ca2+ dependent nitric oxide synthase (cNOS) with small amount of Ca2+ independent nitric oxide synthase (iNOS). Following burn injury,there was a marked increase in iNOS activity with a peak at 8h post-butyl, however, myocardial cNOS activity was found to decline obviously. Parallel to iNOS induction there was a significant increase in myocardial nitric oxide and cyelic GMP production. All these chenges were alleviated by treatment of the rats with dexamethasone. Since increases in cyclic GMP levels in the heart were associated with reduced myocardial contractility, it is possible that enhanced production of nitric oxide by a Ca2+ independent NO synthase accounts, at least in part, for the depression of myocardial contractility seen in burn animals and patients.

  14. Improving Peptide Applications Using Nanotechnology.

    Science.gov (United States)

    Narayanaswamy, Radhika; Wang, Tao; Torchilin, Vladimir P

    2016-01-01

    Peptides are being successfully used in various fields including therapy and drug delivery. With advancement in nanotechnology and targeted delivery carrier systems, suitable modification of peptides has enabled achievement of many desirable goals over-riding some of the major disadvantages associated with the delivery of peptides in vivo. Conjugation or physical encapsulation of peptides to various nanocarriers, such as liposomes, micelles and solid-lipid nanoparticles, has improved their in vivo performance multi-fold. The amenability of peptides to modification in chemistry and functionalization with suitable nanocarriers are very relevant aspects in their use and have led to the use of 'smart' nanoparticles with suitable linker chemistries that favor peptide targeting or release at the desired sites, minimizing off-target effects. This review focuses on how nanotechnology has been used to improve the number of peptide applications. The paper also focuses on the chemistry behind peptide conjugation to nanocarriers, the commonly employed linker chemistries and the several improvements that have already been achieved in the areas of peptide use with the help of nanotechnology.

  15. The Pig PeptideAtlas

    DEFF Research Database (Denmark)

    Hesselager, Marianne Overgaard; Codrea, Marius; Sun, Zhi;

    2016-01-01

    underrepresented in existing repositories. We here present a significantly improved build of the Pig PeptideAtlas, which includes pig proteome data from 25 tissues and three body fluid types mapped to 7139 canonical proteins. The content of the Pig PeptideAtlas reflects actively ongoing research within...... the veterinary proteomics domain, and this article demonstrates how the expression of isoform-unique peptides can be observed across distinct tissues and body fluids. The Pig PeptideAtlas is a unique resource for use in animal proteome research, particularly biomarker discovery and for preliminary design of SRM...

  16. Biodiscovery of aluminum binding peptides

    Science.gov (United States)

    Adams, Bryn L.; Sarkes, Deborah A.; Finch, Amethist S.; Hurley, Margaret M.; Stratis-Cullum, Dimitra

    2013-05-01

    Cell surface peptide display systems are large and diverse libraries of peptides (7-15 amino acids) which are presented by a display scaffold hosted by a phage (virus), bacteria, or yeast cell. This allows the selfsustaining peptide libraries to be rapidly screened for high affinity binders to a given target of interest, and those binders quickly identified. Peptide display systems have traditionally been utilized in conjunction with organic-based targets, such as protein toxins or carbon nanotubes. However, this technology has been expanded for use with inorganic targets, such as metals, for biofabrication, hybrid material assembly and corrosion prevention. While most current peptide display systems employ viruses to host the display scaffold, we have recently shown that a bacterial host, Escherichia coli, displaying peptides in the ubiquitous, membrane protein scaffold eCPX can also provide specific peptide binders to an organic target. We have, for the first time, extended the use of this bacterial peptide display system for the biodiscovery of aluminum binding 15mer peptides. We will present the process of biopanning with macroscopic inorganic targets, binder enrichment, and binder isolation and discovery.

  17. Antitumor Peptides from Marine Organisms

    Directory of Open Access Journals (Sweden)

    Mi Sun

    2011-10-01

    Full Text Available The biodiversity of the marine environment and the associated chemical diversity constitute a practically unlimited resource of new antitumor agents in the field of the development of marine bioactive substances. In this review, the progress on studies of antitumor peptides from marine sources is provided. The biological properties and mechanisms of action of different marine peptides are described; information about their molecular diversity is also presented. Novel peptides that induce apoptosis signal pathway, affect the tubulin-microtubule equilibrium and inhibit angiogenesis are presented in association with their pharmacological properties. It is intended to provide useful information for further research in the fields of marine antitumor peptides.

  18. Solid-phase peptide synthesis

    DEFF Research Database (Denmark)

    Jensen, Knud Jørgen

    2013-01-01

    This chapter provides an introduction to and overview of peptide chemistry with a focus on solid-phase peptide synthesis. The background, the most common reagents, and some mechanisms are presented. This chapter also points to the different chapters and puts them into perspective.......This chapter provides an introduction to and overview of peptide chemistry with a focus on solid-phase peptide synthesis. The background, the most common reagents, and some mechanisms are presented. This chapter also points to the different chapters and puts them into perspective....

  19. Peptides and Food Intake

    Science.gov (United States)

    Sobrino Crespo, Carmen; Perianes Cachero, Aránzazu; Puebla Jiménez, Lilian; Barrios, Vicente; Arilla Ferreiro, Eduardo

    2014-01-01

    The mechanisms for controlling food intake involve mainly an interplay between gut, brain, and adipose tissue (AT), among the major organs. Parasympathetic, sympathetic, and other systems are required for communication between the brain satiety center, gut, and AT. These neuronal circuits include a variety of peptides and hormones, being ghrelin the only orexigenic molecule known, whereas the plethora of other factors are inhibitors of appetite, suggesting its physiological relevance in the regulation of food intake and energy homeostasis. Nutrients generated by food digestion have been proposed to activate G-protein-coupled receptors on the luminal side of enteroendocrine cells, e.g., the L-cells. This stimulates the release of gut hormones into the circulation such as glucagon-like peptide-1 (GLP-1), oxyntomodulin, pancreatic polypeptides, peptide tyrosine tyrosine, and cholecystokinin, which inhibit appetite. Ghrelin is a peptide secreted from the stomach and, in contrast to other gut hormones, plasma levels decrease after a meal and potently stimulate food intake. Other circulating factors such as insulin and leptin relay information regarding long-term energy stores. Both hormones circulate at proportional levels to body fat content, enter the CNS proportionally to their plasma levels, and reduce food intake. Circulating hormones can influence the activity of the arcuate nucleus (ARC) neurons of the hypothalamus, after passing across the median eminence. Circulating factors such as gut hormones may also influence the nucleus of the tractus solitarius (NTS) through the adjacent circumventricular organ. On the other hand, gastrointestinal vagal afferents converge in the NTS of the brainstem. Neural projections from the NTS, in turn, carry signals to the hypothalamus. The ARC acts as an integrative center, with two major subpopulations of neurons influencing appetite, one of them coexpressing neuropeptide Y and agouti-related protein (AgRP) that increases food

  20. Anticancer peptides from bacteria

    Directory of Open Access Journals (Sweden)

    Tomasz M. Karpiński

    2013-08-01

    Full Text Available Cancer is a leading cause of death in the world. The rapid development of medicine and pharmacology allows to create new and effective anticancer drugs. Among modern anticancer drugs are bacterial proteins. Until now has been shown anticancer activity among others azurin and exotoxin A from Pseudomonas aeruginosa, Pep27anal2 from Streptococcus pneumoniae, diphtheria toxin from Corynebacterium diphtheriae, and recently discovered Entap from Enterococcus sp. The study presents the current data regarding the properties, action and anticancer activity of listed peptides.

  1. Nitric oxide negatively regulates mammalian adult neurogenesis

    Science.gov (United States)

    Packer, Michael A.; Stasiv, Yuri; Benraiss, Abdellatif; Chmielnicki, Eva; Grinberg, Alexander; Westphal, Heiner; Goldman, Steven A.; Enikolopov, Grigori

    2003-08-01

    Neural progenitor cells are widespread throughout the adult central nervous system but only give rise to neurons in specific loci. Negative regulators of neurogenesis have therefore been postulated, but none have yet been identified as subserving a significant role in the adult brain. Here we report that nitric oxide (NO) acts as an important negative regulator of cell proliferation in the adult mammalian brain. We used two independent approaches to examine the function of NO in adult neurogenesis. In a pharmacological approach, we suppressed NO production in the rat brain by intraventricular infusion of an NO synthase inhibitor. In a genetic approach, we generated a null mutant neuronal NO synthase knockout mouse line by targeting the exon encoding active center of the enzyme. In both models, the number of new cells generated in neurogenic areas of the adult brain, the olfactory subependyma and the dentate gyrus, was strongly augmented, which indicates that division of neural stem cells in the adult brain is controlled by NO and suggests a strategy for enhancing neurogenesis in the adult central nervous system.

  2. Biomimetic and microbial reduction of nitric oxide

    Energy Technology Data Exchange (ETDEWEB)

    Potter, W.T.; Le, U.; Ronda, S. [Univ. of Tulsa, OK (United States)] [and others

    1995-12-31

    The biomimetic reduction of nitric oxide (NO) to nitrous oxide (N{sub 2}O) by dithiothreitol in the presence of cyanocobalamin and cobalt-centered porphyrins has been investigated. Reactions were monitored directly using Fourier Transform Infrared (FTIR) Spectroscopy vapor-phase spectra. Reaction rates were twofold faster for the corrin than for the cobalt-centered porphyrins. The stoichiometry showed the loss of two molecules of NO per molecule of N{sub 2}O produced. We have also demonstrated that the facultative anaerobe and chemoautotroph, Thiobacillus denitrificans, can be cultured anoxically in batch reactors using NO as a terminal electron acceptor with reduction to elemental nitrogen (N{sub 2}). We have proposed that the concentrated stream of NO{sub x}, as obtained from certain regenerable processes for the gas desulfurization and NO{sub x} removal, could be converted to N{sub 2} for disposal by contact with a culture of T. denitrificans. Four heterotrophic bacteria have also been identified that may be grown in batch cultures with succinate, yeast extract, or heat and alkali pretreated sewage sludge as carbon and energy sources and NO as a terminal electron acceptor. These are Paracoccus dentrificans, Pseudomonas denitrificans, Alcaligens denitrificans, and Thiophaera pantotropha.

  3. Superhydrophobic nitric oxide-releasing xerogels.

    Science.gov (United States)

    Storm, Wesley L; Youn, Jonghae; Reighard, Katelyn P; Worley, Brittany V; Lodaya, Hetali M; Shin, Jae Ho; Schoenfisch, Mark H

    2014-08-01

    Superhydrophobic nitric oxide (NO)-releasing xerogels were prepared by spray-coating a fluorinated silane/silica composite onto N-diazeniumdiolate NO donor-modified xerogels. The thickness of the superhydrophobic layer was used to extend NO release durations from 59 to 105h. The resulting xerogels were stable, maintaining superhydrophobicity for up to 1month (the longest duration tested) when immersed in solution, with no leaching of silica or undesirable fragmentation detected. The combination of superhydrophobicity and NO release reduced viable Pseudomonas aeruginosa adhesion by >2-logs. The killing effect of NO was demonstrated at longer bacterial contact times, with superhydrophobic NO-releasing xerogels resulting in 3.8-log reductions in adhered viable bacteria vs. controls. With no observed toxicity to L929 murine fibroblasts, NO-releasing superhydrophobic membranes may be valuable antibacterial coatings for implants as they both reduce adhesion and kill bacteria that do adhere. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  4. Hemoglobin: A Nitric-Oxide Dioxygenase

    Directory of Open Access Journals (Sweden)

    Paul R. Gardner

    2012-01-01

    Full Text Available Members of the hemoglobin superfamily efficiently catalyze nitric-oxide dioxygenation, and when paired with native electron donors, function as NO dioxygenases (NODs. Indeed, the NOD function has emerged as a more common and ancient function than the well-known role in O2 transport-storage. Novel hemoglobins possessing a NOD function continue to be discovered in diverse life forms. Unique hemoglobin structures evolved, in part, for catalysis with different electron donors. The mechanism of NOD catalysis by representative single domain hemoglobins and multidomain flavohemoglobin occurs through a multistep mechanism involving O2 migration to the heme pocket, O2 binding-reduction, NO migration, radical-radical coupling, O-atom rearrangement, nitrate release, and heme iron re-reduction. Unraveling the physiological functions of multiple NODs with varying expression in organisms and the complexity of NO as both a poison and signaling molecule remain grand challenges for the NO field. NOD knockout organisms and cells expressing recombinant NODs are helping to advance our understanding of NO actions in microbial infection, plant senescence, cancer, mitochondrial function, iron metabolism, and tissue O2 homeostasis. NOD inhibitors are being pursued for therapeutic applications as antibiotics and antitumor agents. Transgenic NOD-expressing plants, fish, algae, and microbes are being developed for agriculture, aquaculture, and industry.

  5. Nitric oxide and teratogenesis: an update.

    Science.gov (United States)

    Tiboni, Gian Mario; Ponzano, Adalisa

    2014-01-01

    Nitric oxide (NO), generated by NO synthase (NOS) enzymes, is an important bioactive molecule involved in the regulation of several biological phenomena that are crucial for organogenesis, including gene expression, cell growth, matrix remolding, proliferation, differentiation and apoptosis. The expression of NOS isoforms in embryonic tissues is temporally and spatially regulated, and disruption of endogenous NO can lead to developmental defects. Maternal treatment with pan NOS inhibitors during early organogenesis caused severe malformations of the axial skeleton. In utero exposure during the fetal period induced limb reduction defects of vascular origin. Knock-out mice have been used to define the role of the various NOS isoforms on the origin of the abnormal development. Cardiovascular malformations, limb reduction defects, reduced growth and reduced survival have been observed in knock-out mice with targeted disruption of endothelial NOS (eNOS). Limited morphological changes were observed in mice lacking inducible NOS (iNOS) or neuronal NOS n(NOS). Results obtained with in vitro studies suggest that optimal levels of NO are required for neural tube closure. Disregulation of NO production was also recently proposed as a contributing mechanism in the origin of malformations associated with exposure to known environmental teratogens, such as valproic acid, thalidomide, copper deficiency, and diabetes.

  6. Dietary Nitrate, Nitric Oxide, and Cardiovascular Health.

    Science.gov (United States)

    Bondonno, Catherine P; Croft, Kevin D; Hodgson, Jonathan M

    2016-09-09

    Emerging evidence strongly suggests that dietary nitrate, derived in the diet primarily from vegetables, could contribute to cardiovascular health via effects on nitric oxide (NO) status. NO plays an essential role in cardiovascular health. It is produced via the classical L-arginine-NO-synthase pathway and the recently discovered enterosalivary nitrate-nitrite-NO pathway. The discovery of this alternate pathway has highlighted dietary nitrate as a candidate for the cardioprotective effect of a diet rich in fruit and vegetables. Clinical trials with dietary nitrate have observed improvements in blood pressure, endothelial function, ischemia-reperfusion injury, arterial stiffness, platelet function, and exercise performance with a concomitant augmentation of markers of NO status. While these results are indicative of cardiovascular benefits with dietary nitrate intake, there is still a lingering concern about nitrate in relation to methemoglobinemia, cancer, and cardiovascular disease. It is the purpose of this review to present an overview of NO and its critical role in cardiovascular health; to detail the observed vascular benefits of dietary nitrate intake through effects on NO status as well as to discuss the controversy surrounding the possible toxic effects of nitrate.

  7. Nitric oxide and cardiovascular risk factors

    Directory of Open Access Journals (Sweden)

    Livio Dai Cas

    2007-06-01

    Full Text Available The endothelium is a dynamic organ with many properties that takes part in the regulation of the principal mechanisms of vascular physiology. Its principal functions include the control of blood-tissue exchange and permeability, the vascular tonus, and the modulation of inflammatory or coagulatory mechanisms. Many vasoactive molecules, produced by the endothelium, are involved in the control of these functions. The most important is nitric oxide (NO, a gaseous molecule electrically neutral with an odd number of electrons that gives the molecule chemically reactive radical properties. Already known in the twentieth century, NO, sometimes considered as a dangerous molecule, recently valued as an important endogenous vasodilator factor. Recently, it was discovered that it is involved in several physiological mechanisms of endothelial protection (Tab. I. In 1992, Science elected it as “molecule of the year”; 6 yrs later three American researchers (Louis Ignarro, Robert Furchgott and Fried Murad obtained a Nobel Prize for Medicine and Physiology “for their discoveries about NO as signal in the cardiovascular system”.

  8. Nitric Oxide Synthases in Heart Failure

    Science.gov (United States)

    Carnicer, Ricardo; Crabtree, Mark J.; Sivakumaran, Vidhya

    2013-01-01

    Abstract Significance: The regulation of myocardial function by constitutive nitric oxide synthases (NOS) is important for the maintenance of myocardial Ca2+ homeostasis, relaxation and distensibility, and protection from arrhythmia and abnormal stress stimuli. However, sustained insults such as diabetes, hypertension, hemodynamic overload, and atrial fibrillation lead to dysfunctional NOS activity with superoxide produced instead of NO and worse pathophysiology. Recent Advances: Major strides in understanding the role of normal and abnormal constitutive NOS in the heart have revealed molecular targets by which NO modulates myocyte function and morphology, the role and nature of post-translational modifications of NOS, and factors controlling nitroso-redox balance. Localized and differential signaling from NOS1 (neuronal) versus NOS3 (endothelial) isoforms are being identified, as are methods to restore NOS function in heart disease. Critical Issues: Abnormal NOS signaling plays a key role in many cardiac disorders, while targeted modulation may potentially reverse this pathogenic source of oxidative stress. Future Directions: Improvements in the clinical translation of potent modulators of NOS function/dysfunction may ultimately provide a powerful new treatment for many hearts diseases that are fueled by nitroso-redox imbalance. Antioxid. Redox Signal. 18, 1078–1099. PMID:22871241

  9. Exploring Protein-Peptide Binding Specificity through Computational Peptide Screening.

    Directory of Open Access Journals (Sweden)

    Arnab Bhattacherjee

    2013-10-01

    Full Text Available The binding of short disordered peptide stretches to globular protein domains is important for a wide range of cellular processes, including signal transduction, protein transport, and immune response. The often promiscuous nature of these interactions and the conformational flexibility of the peptide chain, sometimes even when bound, make the binding specificity of this type of protein interaction a challenge to understand. Here we develop and test a Monte Carlo-based procedure for calculating protein-peptide binding thermodynamics for many sequences in a single run. The method explores both peptide sequence and conformational space simultaneously by simulating a joint probability distribution which, in particular, makes searching through peptide sequence space computationally efficient. To test our method, we apply it to 3 different peptide-binding protein domains and test its ability to capture the experimentally determined specificity profiles. Insight into the molecular underpinnings of the observed specificities is obtained by analyzing the peptide conformational ensembles of a large number of binding-competent sequences. We also explore the possibility of using our method to discover new peptide-binding pockets on protein structures.

  10. Concentrations of Nitric Oxide in Rat Brain Tissues after Diffuse Brain Injury and Neuroprotection by the Selective Inducible Nitric Oxide Synthase Inhibitor Aminoguanidine

    Institute of Scientific and Technical Information of China (English)

    Yi-bao Wang; Shao-wu Ou; Guang-yu Li; Yun-hui Liu

    2005-01-01

    @@ To investigate the effects of nitric oxide (NO) and the selective inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine (AG) on trauma, we explored the concentrations of nitric oxide in rat brain tissues at different time stamps after diffuse brain injury (DBI) with or without AG treatment.

  11. A cold-induced phytosulfokine peptide is related to the improvement of loquat fruit chilling tolerance.

    Science.gov (United States)

    Song, Huwei; Wang, Xinfeng; Hu, Weicheng; Yang, Xianghui; Diao, Enjie; Shen, Ting; Qiang, Qian

    2017-10-01

    A novel peptidomics approach was used to discover cold-induced peptides in loquat fruit. Twenty unique peptides derived from 18 proproteins were identified, and they were involved in sugar signalling, protein metabolism and stress response. The quantitative analysis revealed 7 peptides with more than 2-fold upregulation, especially a 4.96-fold increase detected in the phytosulfokine (PSK) peptide. To further evaluate effects of PSK1 on fruit chilling tolerance, weight loss, firmness and internal browning were investigated in PSK1-treated loquat fruit at 0°C. By contrast, these chilling injury symptoms were effectively reduced by PSK1. PSK1 markedly delayed decreases of ATP content and energy charge. The PSK1-treated fruit exhibited significantly lower activities of cell-wall degrading enzymes and transcripts of genes related to lignin synthesis. Our results demonstrated that PSK1 improves chilling tolerance of loquat fruit by maintaining high energy status and cell integrity. Peptidomics analysis provides a promising tool to discover some key peptides. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Inefficient constitutive inhibition of P2X3 receptors by brain natriuretic peptide system contributes to sensitization of trigeminal sensory neurons in a genetic mouse model of familial hemiplegic migraine.

    Science.gov (United States)

    Marchenkova, Anna; Vilotti, Sandra; Ntamati, Niels; van den Maagdenberg, Arn Mjm; Nistri, Andrea

    2016-01-01

    On trigeminal ganglion neurons, pain-sensing P2X3 receptors are constitutively inhibited by brain natriuretic peptide via its natriuretic peptide receptor-A. This inhibition is associated with increased P2X3 serine phosphorylation and receptor redistribution to non-lipid raft membrane compartments. The natriuretic peptide receptor-A antagonist anantin reverses these effects. We studied whether P2X3 inhibition is dysfunctional in a genetic familial hemiplegic migraine type-1 model produced by introduction of the human pathogenic R192Q missense mutation into the mouse CACNA1A gene (knock-in phenotype). This model faithfully replicates several properties of familial hemiplegic migraine type-1, with gain-of-function of CaV2.1 Ca(2+) channels, raised levels of the algogenic peptide calcitonin gene-related peptide, and enhanced activity of P2X3 receptors in trigeminal ganglia. In knock-in neurons, anantin did not affect P2X3 receptor activity, membrane distribution, or serine phosphorylation level, implying ineffective inhibition by the constitutive brain natriuretic peptide/natriuretic peptide receptor-A pathway. However, expression and functional properties of this pathway remained intact together with its ability to downregulate TRPV1 channels. Reversing the familial hemiplegic migraine type-1 phenotype with the CaV2.1-specific antagonist, ω-agatoxin IVA restored P2X3 activity to wild-type level and enabled the potentiating effects of anantin again. After blocking calcitonin gene-related peptide receptors, P2X3 receptors exhibited wild-type properties and were again potentiated by anantin. P2X3 receptors on mouse trigeminal ganglion neurons are subjected to contrasting modulation by inhibitory brain natriuretic peptide and facilitatory calcitonin gene-related peptide that both operate via complex intracellular signaling. In the familial hemiplegic migraine type-1 migraine model, the action of calcitonin gene-related peptide appears to prevail over brain natriuretic

  13. Nitric oxide production and nitric oxide synthase immunoreactivity in Naegleria fowleri.

    Science.gov (United States)

    Rojas-Hernández, Saúl; Rodríguez-Monroy, Marco A; Moreno-Fierros, Leticia; Jarillo-Luna, Adriana; Carrasco-Yepez, Marisela; Miliar-García, Angel; Campos-Rodríguez, Rafael

    2007-07-01

    Free-living ameba Naegleria fowleri produces an acute and fatal infectious disease called primary amebic meningoencephalitis (PAM), whose pathophysiological mechanism is largely unknown. The aim of this study was to investigate the role of nitric oxide (NO) in PAM. Although NO has a cytotoxic effect on various parasites, it is produced by others as part of the pathology, as is the case with Entamoeba histolytica. To test for the production of NO, we analyzed whether antibodies against mammalian NO synthase isoforms (neuronal, inducible, and endothelial) presented immunoreactivity to N. fowleri proteins. We found that the trophozoites produced NO in vitro. The Western blot results, which showed N. fowleri trophozoites, contained proteins that share epitopes with the three described mammalian NOS, but have relative molecular weights different than those described in the literature, suggesting that N. fowleri may contain undescribed NOS isoforms. Moreover, we found that trophozoites reacted to the NOS2 antibody, in amebic cultures as well as in the mouse brain infected with N. fowleri, suggesting that nitric oxide may participate in the pathogenesis of PAM. Further research aimed at determining whether N. fowleri contains active novel NOS isoforms could lead to the design of new therapies against this parasite.

  14. Extraction of nitric acid, uranyl nitrate, and bismuth nitrate from aqueous nitric acid solutions with CMPO

    Energy Technology Data Exchange (ETDEWEB)

    Spencer, B.B.

    1995-08-01

    DOE sponsored development of the transuranium extraction (TRUEX) process for removing actinides from radioactive wastes. The solvent is a mixture of CMPO and TBP. Since the extraction characteristics of CMPO are not as well understood as those of TBP, the extraction of nitric acid, uranyl nitrate, and bismuth nitrate with CMPO (dissolved in n-dodecane) were studied. Results indicate that CMPO extracts nitric acid with a 1:1 stoichiometry; equilibrium constant is 2. 660{plus_minus}0.092 at 25 C, and extraction enthalpy is -5. 46{plus_minus}0.46 kcal/mol. Slope analysis indicates that uranyl nitrate extracts with a mixed equilibria of 1:1 and 2:1 stoichiometries in nearly equal proportion. Equil. constant of the 2: 1 extraction was 1.213 {times} 10{sup 6}{plus_minus}3.56 {times} 10{sup 4} at 25 C; reaction enthalpy was -9.610{plus_minus}0.594 kcal/mol. Nitration complexation constant is 8.412{plus_minus}0.579, with an enthalpy of -10.72{plus_minus}1.87 kcal/mol. Bismuth nitrate also extracts with a mixed equilibria of (perhaps) 1:1 and 2:1 stoichiometries. A 2:1 extraction equilibrium and a nitrate complexation adequately model the data. Kinetics and enthalpies were also measured.

  15. Novel Genes Related to Ceftriaxone Resistance Found among Ceftriaxone-Resistant Neisseria gonorrhoeae Strains Selected In Vitro.

    Science.gov (United States)

    Gong, Zijian; Lai, Wei; Liu, Min; Hua, Zhengshuang; Sun, Yayin; Xu, Qingfang; Xia, Yue; Zhao, Yue; Xie, Xiaoyuan

    2016-04-01

    The emergence of ceftriaxone-resistantNeisseria gonorrhoeaeis currently a global public health concern. However, the mechanism of ceftriaxone resistance is not yet fully understood. To investigate the potential genes related to ceftriaxone resistance inNeisseria gonorrhoeae, we subcultured six gonococcal strains with increasing concentrations of ceftriaxone and isolated the strains that became resistant. After analyzing several frequently reported genes involved in ceftriaxone resistance, we found only a single mutation inpenA(A501V). However, differential analysis of the genomes and transcriptomes between pre- and postselection strains revealed many other mutated genes as well as up- and downregulated genes. Transformation of the mutatedpenAgene into nonresistant strains increased the MIC between 2.0- and 5.3-fold, and transformation of mutatedftsXincreased the MIC between 3.3- and 13.3-fold. Genes encoding the ABC transporters FarB, Tfq, Hfq, and ExbB were overexpressed, whilepilM,pilN, andpilQwere downregulated. Furthermore, the resistant strain developed cross-resistance to penicillin and cefuroxime, had an increased biochemical metabolic rate, and presented fitness defects such as prolonged growth time and downregulated PilMNQ. In conclusion, antimicrobial pressure could result in the emergence of ceftriaxone resistance, and the evolution of resistance ofNeisseria gonorrhoeaeto ceftriaxone is a complicated process at both the pretranscriptional and posttranscriptional levels, involving several resistance mechanisms of increased efflux and decreased entry.

  16. Genome Analysis of a Zygomycete Fungus Choanephora cucurbitarum Elucidates Necrotrophic Features Including Bacterial Genes Related to Plant Colonization

    Science.gov (United States)

    Min, Byoungnam; Park, Ji-Hyun; Park, Hongjae; Shin, Hyeon-Dong; Choi, In-Geol

    2017-01-01

    A zygomycete fungus, Choanephora cucurbitarum is a plant pathogen that causes blossom rot in cucurbits and other plants. Here we report the genome sequence of Choanephora cucurbitarum KUS-F28377 isolated from squash. The assembled genome has a size of 29.1 Mbp and 11,977 protein-coding genes. The genome analysis indicated that C. cucurbitarum may employ a plant pathogenic mechanism similar to that of bacterial plant pathogens. The genome contained 11 genes with a Streptomyces subtilisin inhibitor-like domain, which plays an important role in the defense against plant immunity. This domain has been found only in bacterial genomes. Carbohydrate active enzyme analysis detected 312 CAZymes in this genome where carbohydrate esterase family 6, rarely found in dikaryotic fungal genomes, was comparatively enriched. The comparative genome analysis showed that the genes related to sexual communication such as the biosynthesis of β-carotene and trisporic acid were conserved and diverged during the evolution of zygomycete genomes. Overall, these findings will help us to understand how zygomycetes are associated with plants. PMID:28091548

  17. Discovery of genes related to witches broom disease in Paulownia tomentosa × Paulownia fortunei by a De Novo assembled transcriptome.

    Directory of Open Access Journals (Sweden)

    Rongning Liu

    Full Text Available In spite of its economic importance, very little molecular genetics and genomic research has been targeted at the family Paulownia spp. The little genetic information on this plant is a big obstacle to studying the mechanisms of its ability to resist Paulownia Witches' Broom (PaWB disease. Analysis of the Paulownia transcriptome and its expression profile data are essential to extending the genetic resources on this species, thus will greatly improves our studies on Paulownia. In the current study, we performed the de novo assembly of a transcriptome on P. tomentosa × P. fortunei using the short-read sequencing technology (Illumina. 203,664 unigenes with a mean length of 1,328 bp was obtained. Of these unigenes, 32,976 (30% of all unigenes containing complete structures were chosen. Eukaryotic clusters of orthologous groups, gene orthology, and the Kyoto Encyclopedia of Genes and Genomes annotations were performed of these unigenes. Genes related to PaWB disease resistance were analyzed in detail. To our knowledge, this is the first study to elucidate the genetic makeup of Paulownia. This transcriptome provides a quick way to understanding Paulownia, increases the number of gene sequences available for further functional genomics studies and provides clues to the identification of potential PaWB disease resistance genes. This study has provided a comprehensive insight into gene expression profiles at different states, which facilitates the study of each gene's roles in the developmental process and in PaWB disease resistance.

  18. Discovery of genes related to witches broom disease in Paulownia tomentosa × Paulownia fortunei by a De Novo assembled transcriptome.

    Science.gov (United States)

    Liu, Rongning; Dong, Yanpeng; Fan, Guoqiang; Zhao, Zhenli; Deng, Minjie; Cao, Xibing; Niu, Suyan

    2013-01-01

    In spite of its economic importance, very little molecular genetics and genomic research has been targeted at the family Paulownia spp. The little genetic information on this plant is a big obstacle to studying the mechanisms of its ability to resist Paulownia Witches' Broom (PaWB) disease. Analysis of the Paulownia transcriptome and its expression profile data are essential to extending the genetic resources on this species, thus will greatly improves our studies on Paulownia. In the current study, we performed the de novo assembly of a transcriptome on P. tomentosa × P. fortunei using the short-read sequencing technology (Illumina). 203,664 unigenes with a mean length of 1,328 bp was obtained. Of these unigenes, 32,976 (30% of all unigenes) containing complete structures were chosen. Eukaryotic clusters of orthologous groups, gene orthology, and the Kyoto Encyclopedia of Genes and Genomes annotations were performed of these unigenes. Genes related to PaWB disease resistance were analyzed in detail. To our knowledge, this is the first study to elucidate the genetic makeup of Paulownia. This transcriptome provides a quick way to understanding Paulownia, increases the number of gene sequences available for further functional genomics studies and provides clues to the identification of potential PaWB disease resistance genes. This study has provided a comprehensive insight into gene expression profiles at different states, which facilitates the study of each gene's roles in the developmental process and in PaWB disease resistance.

  19. A peptide factor secreted by Staphylococcus pseudintermedius exhibits properties of both bacteriocins and virulence factors

    Science.gov (United States)

    Wladyka, Benedykt; Piejko, Marcin; Bzowska, Monika; Pieta, Piotr; Krzysik, Monika; Mazurek, Łukasz; Guevara-Lora, Ibeth; Bukowski, Michał; Sabat, Artur J.; Friedrich, Alexander W.; Bonar, Emilia; Międzobrodzki, Jacek; Dubin, Adam; Mak, Paweł

    2015-01-01

    Staphylococcus pseudintermedius is a common commensal bacterium colonizing the skin and mucosal surfaces of household animals. However, it has recently emerged as a dangerous opportunistic pathogen, comparable to S. aureus for humans. The epidemiological situation is further complicated by the increasing number of methicillin-resistant S. pseudintermedius infections and evidence of gene transmission driving antibiotic resistance between staphylococci colonizing human and zoonotic hosts. In the present study, we describe a unique peptide, BacSp222, that possesses features characteristic of both bacteriocins and virulence factors. BacSp222 is secreted in high quantities by S. pseudintermedius strain 222 isolated from dog skin lesions. This linear, fifty-amino-acid highly cationic peptide is plasmid-encoded and does not exhibit significant sequence similarities to any other known peptides or proteins. BacSp222 kills gram-positive bacteria (at doses ranging from 0.1 to several micromol/l) but also demonstrates significant cytotoxic activities towards eukaryotic cells at slightly higher concentrations. Moreover, at nanomolar concentrations, the peptide also possesses modulatory properties, efficiently enhancing interferon gamma-induced nitric oxide release in murine macrophage-like cell lines. BacSp222 appears to be one of the first examples of multifunctional peptides that breaks the convention of splitting bacteriocins and virulence factors into two unrelated groups. PMID:26411997

  20. A peptide factor secreted by Staphylococcus pseudintermedius exhibits properties of both bacteriocins and virulence factors.

    Science.gov (United States)

    Wladyka, Benedykt; Piejko, Marcin; Bzowska, Monika; Pieta, Piotr; Krzysik, Monika; Mazurek, Łukasz; Guevara-Lora, Ibeth; Bukowski, Michał; Sabat, Artur J; Friedrich, Alexander W; Bonar, Emilia; Międzobrodzki, Jacek; Dubin, Adam; Mak, Paweł

    2015-09-28

    Staphylococcus pseudintermedius is a common commensal bacterium colonizing the skin and mucosal surfaces of household animals. However, it has recently emerged as a dangerous opportunistic pathogen, comparable to S. aureus for humans. The epidemiological situation is further complicated by the increasing number of methicillin-resistant S. pseudintermedius infections and evidence of gene transmission driving antibiotic resistance between staphylococci colonizing human and zoonotic hosts. In the present study, we describe a unique peptide, BacSp222, that possesses features characteristic of both bacteriocins and virulence factors. BacSp222 is secreted in high quantities by S. pseudintermedius strain 222 isolated from dog skin lesions. This linear, fifty-amino-acid highly cationic peptide is plasmid-encoded and does not exhibit significant sequence similarities to any other known peptides or proteins. BacSp222 kills gram-positive bacteria (at doses ranging from 0.1 to several micromol/l) but also demonstrates significant cytotoxic activities towards eukaryotic cells at slightly higher concentrations. Moreover, at nanomolar concentrations, the peptide also possesses modulatory properties, efficiently enhancing interferon gamma-induced nitric oxide release in murine macrophage-like cell lines. BacSp222 appears to be one of the first examples of multifunctional peptides that breaks the convention of splitting bacteriocins and virulence factors into two unrelated groups.

  1. Inhibitory activity of the peptides derived from buffalo prolactin on angiogenesis

    Indian Academy of Sciences (India)

    Jaeok Lee; Syamantak Majumder; Suvro Chatterjee; Kambadur Muralidhar

    2011-06-01

    The peptide fragments obtained by cathepsin digestion of purified buffalo prolactin (buPRL) monomer have been characterized using SDS-PAGE and FPLC with regard to size and pI. Their antiangiogenic activity was tested in chick embryo chorioallantoic membrane (CAM) assay and the human endothelial cells wound healing assay. Antiangiogenic activity was observed in cathepsin-cleaved fragments from buPRL. Further, a peptide sequence 45A-46Q-47G-48K-49G-50F-51I-52T-53M-54A-55L-56N-57S-58C, which matched with human somatostatin (hSST), a known antiangiogenic factor, was located in the second loop between the first and second α-helices in the threedimensional structure of buPRL, obtained by homology modelling. The synthetic peptide matching with SST sequence was found to exhibit antiangiogenic activity in both in vitro and ex vivo assays. It was also observed that all the peptides related to buPRL could antagonize the vascular endothelial growth factor (VEGF) and bradykinin (BK)-dependent production of endothelial nitric oxide (NO), which is a pre-requisite for endothelial tube formation. It is concluded therefore that an internal sequence in buPRL and peptide fragments derived from cathepsin-digested buPRL exhibit antiangiogenic activities.

  2. Endogenous opioid peptides and epilepsy

    NARCIS (Netherlands)

    J. Haffmans (Judith)

    1985-01-01

    textabstractIn recent years a large number of pept:ides, many of which were originall.y characterized in non-neural tissues, have been reported to be present in the central nervous system ( CNS) . The detection of these peptides within the CNS has raised many questions regarding their source and mec

  3. Urinary Peptides in Rett Syndrome.

    Science.gov (United States)

    Solaas, K. M.; Skjeldal, O.; Gardner, M. L. G.; Kase, B. F.; Reichelt, K. L.

    2002-01-01

    A study found a significantly higher level of peptides in the urine of 53 girls with Rett syndrome compared with controls. The elevation was similar to that in 35 girls with infantile autism. Levels of peptides were lower in girls with classic Rett syndrome than those with congenital Rett syndrome. (Contains references.) (Author/CR)

  4. Biosynthesis of cardiac natriuretic peptides

    DEFF Research Database (Denmark)

    Goetze, Jens Peter

    2010-01-01

    Cardiac-derived peptide hormones were identified more than 25 years ago. An astonishing amount of clinical studies have established cardiac natriuretic peptides and their molecular precursors as useful markers of heart disease. In contrast to the clinical applications, the biogenesis of cardiac...

  5. Synthetic peptides for antibody production

    NARCIS (Netherlands)

    Zegers, N.D.

    1995-01-01

    Synthetic peptides are useful tools for the generation of antibodies. The use of antibodies as specific reagents in inununochemical assays is widely applied. In this chapter, the application of synthetic peptides for the generation of antibodies is described. The different steps that lead to the uni

  6. Peptide-LNA oligonucleotide conjugates

    DEFF Research Database (Denmark)

    Astakhova, I Kira; Hansen, Lykke Haastrup; Vester, Birte

    2013-01-01

    properties, peptides were introduced into oligonucleotides via a 2'-alkyne-2'-amino-LNA scaffold. Derivatives of methionine- and leucine-enkephalins were chosen as model peptides of mixed amino acid content, which were singly and doubly incorporated into LNA/DNA strands using highly efficient copper......Although peptide-oligonucleotide conjugates (POCs) are well-known for nucleic acids delivery and therapy, reports on internal attachment of peptides to oligonucleotides are limited in number. To develop a convenient route for preparation of internally labeled POCs with improved biomedical......(i)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry. DNA/RNA target binding affinity and selectivity of the resulting POCs were improved in comparison to LNA/DNA mixmers and unmodified DNA controls. This clearly demonstrates that internal attachment of peptides to oligonucleotides can significantly...

  7. Transport of nitric oxide by perfluorocarbon emulsion.

    Science.gov (United States)

    Ortiz, Daniel; Cabrales, Pedro; Briceño, Juan C

    2013-01-01

    Perfluorocarbon (PFC) emulsions can transport and release various gases based on concentration gradients. The objective of this study was to determine the possibility of carrying and delivering exogenous nitric oxide (NO) into the circulation by simply loading PFC emulsion with NO prior infusion. PFC was equilibrated with room air (PFC) or 300 ppm NO (PFC-NO) at atmospheric pressure. Isotonic saline solution was used as a volume control (Saline). PFC and PFC-NO were infused at a dose of 3.5 mL/kg in the hamster window chamber model. Blood chemistry, and systemic and microvascular hemodynamic response were measured. Infusion of PFC preloaded with NO reduced blood pressure, induced microvascular vasodilation and increased capillary perfusion; although these changes lasted less than 30 min post infusion. On the other hand, infusion of PFC (without NO) produced vasoconstriction; however, the vasoconstriction was followed by vasodilatation at 30 min post infusion. Plasma nitrite and nitrate increased 15 min after infusion of NO preloaded PFC compared with PFC, 60 min after infusion nitrite and nitrate were not different, and 90 min after infusion plasma S-nitrosothiols increased in both groups. Infusion of NO preloaded PFC resulted in acute vascular relaxation, where as infusion of PFC (without NO) produced vasoconstriction, potentially due to NO sequestration by the PFC micelles. The late effects of PFC infusion are due to NO redistribution and plasma S-nitrosothiols. Gas solubility in PFC can provide a tool to modulate plasma vasoactive NO forms availability and improve microcirculatory function and promote increased blood flow.

  8. Nitric oxide in adaptation to altitude.

    Science.gov (United States)

    Beall, Cynthia M; Laskowski, Daniel; Erzurum, Serpil C

    2012-04-01

    This review summarizes published information on the levels of nitric oxide gas (NO) in the lungs and NO-derived liquid-phase molecules in the acclimatization of visitors newly arrived at altitudes of 2500 m or more and adaptation of populations whose ancestors arrived thousands of years ago. Studies of acutely exposed visitors to high altitude focus on the first 24-48 h with just a few extending to days or weeks. Among healthy visitors, NO levels in the lung, plasma, and/or red blood cells fell within 2h, but then returned toward baseline or slightly higher by 48 h and increased above baseline by 5 days. Among visitors ill with high-altitude pulmonary edema at the time of the study or in the past, NO levels were lower than those of their healthy counterparts. As for highland populations, Tibetans had NO levels in the lung, plasma, and red blood cells that were at least double and in some cases orders of magnitude greater than other populations regardless of altitude. Red blood cell-associated nitrogen oxides were more than 200 times higher. Other highland populations had generally higher levels although not to the degree shown by Tibetans. Overall, responses of those acclimatized and those presumed to be adapted are in the same direction, although the Tibetans have much larger responses. Missing are long-term data on lowlanders at altitude showing how similar they become to the Tibetan phenotype. Also missing are data on Tibetans at low altitude to see the extent to which their phenotype is a response to the immediate environment or expressed constitutively. The mechanisms causing the visitors' and the Tibetans' high levels of NO and NO-derived molecules at altitude remain unknown. Limited data suggest processes including hypoxic upregulation of NO synthase gene expression, hemoglobin-NO reactions, and genetic variation. Gains in understanding will require integrating appropriate methods and measurement techniques with indicators of adaptive function under hypoxic

  9. Anticonvulsant drugs, oxidative stress and nitric oxide.

    Science.gov (United States)

    Vega Rasgado, L A; Ceballos Reyes, G M; Vega-Diaz, M F

    2011-01-01

    Nitric Oxide (NO) is thought to play a fundamental role in the genesis and the spreading of epileptiform hyperactivity, although its function is unclear and controversial. As a free radical, NO may cause oxidative stress, which is emerging as an important mechanism in the etiology of seizure-induced neuronal death. Here we investigated the role of NO in seizure mechanisms through oxidative stress generation by studying the effect of anticonvulsant drugs such as amino oxyacetic acid (AAOA), valproate (VALP), diazepam (DIAZ) and gabapentin (GBPTNA) on oxidative stress in the brain, estimated as free carbonyls by the method of Dalle and Rossi, and by measuring NO by the indirect method based on the Griess reaction. Results show that, except for AAOA and VALP, anticonvulsants did not significantly affect or decreased free carbonyls, but reversed the oxidative stress produced by pentylenetetrazole (PTZ) induced convulsions. Anticonvulsants except AAOA diminished NO levels and with the exception of VALP, counteracted the increase in NO generated by PTZ. Anticonvulsants decreased oxidative stress and NO especially in hippocampus (HI) and cortex (CX), and reversed PTZ effects on both parameters. PTZ diminished NO in HI, which could be explained since PTZ caused an increase on endothelial NO synthase but a decrease in neuronal NOS expression in this brain area. Since the drugs studied are modulating GABA levels, our results suggest that seizures generated by alterations in GABAergic transmission produce oxidative stress caused by NO, which can be reversed by anticonvulsants. The effects described differ among the brain regions studied and the NO synthase isoform affected.

  10. Nitric oxide scavenging by red cell microparticles.

    Science.gov (United States)

    Liu, Chen; Zhao, Weixin; Christ, George J; Gladwin, Mark T; Kim-Shapiro, Daniel B

    2013-12-01

    Red cell microparticles form during the storage of red blood cells and in diseases associated with red cell breakdown and asplenia, including hemolytic anemias such as sickle cell disease. These small phospholipid vesicles that are derived from red blood cells have been implicated in the pathogenesis of transfusion of aged stored blood and hemolytic diseases, via activation of the hemostatic system and effects on nitric oxide (NO) bioavailability. Red cell microparticles react with the important signaling molecule NO almost as fast as cell-free hemoglobin, about 1000 times faster than red-cell-encapsulated hemoglobin. The degree to which this fast reaction with NO by red cell microparticles influences NO bioavailability depends on several factors that are explored here. In the context of stored blood preserved in ADSOL, we find that both cell-free hemoglobin and red cell microparticles increase as a function of duration of storage, and the proportion of extra erythrocytic hemoglobin in the red cell microparticle fraction is about 20% throughout storage. Normalized by hemoglobin concentration, the NO-scavenging ability of cell-free hemoglobin is slightly higher than that of red cell microparticles as determined by a chemiluminescence NO-scavenging assay. Computational simulations show that the degree to which red cell microparticles scavenge NO will depend substantially on whether they enter the cell-free zone next to the endothelial cells. Single-microvessel myography experiments performed under laminar flow conditions demonstrate that microparticles significantly enter the cell-free zone and inhibit acetylcholine, endothelial-dependent, and NO-dependent vasodilation. Taken together, these data suggest that as little as 5 μM hemoglobin in red cell microparticles, an amount formed after the infusion of one unit of aged stored packed red blood cells, has the potential to reduce NO bioavailability and impair endothelial-dependent vasodilation.

  11. Role of Regulatory Peptide in Pathogenesis of Shock

    Institute of Scientific and Technical Information of China (English)

    董林旺; 常英姿; 佟利家; 汤健; 苏静怡; 唐朝枢

    1994-01-01

    The present study evaluated the pathogenetic roles of three kinds of regulatory peptide. The results showed that (i) plasma endothelin(ET) level elevated significantly in septic shock rats, persistent intravenous drip of low doses ET caused development of shock state in normal rats and the irreversible outcome of light hemorrhagic shock. Furthermore, i. v. administration of specific ET-antiserum was significantly effective to septic shock rats, (Ⅱ) Plasma calcitonin gene-related peptide (CGRP) increased by 260% in septic shock rats, i. v. drip of low doses CGRP both in early and late sepsis were effective to shock rats, (Ⅱi) An-giotensin-Ⅱ (ANG-Ⅱ) contents of heart and aorta increased dramatically both in early and late septic shock, and inhibiting its increase with Captopril in late sepsis significantly improved the shock state, but results were inverse in early sepsis. It could be concluded that ET was one of the most important factors participating in the pathogenesis of shock, CGRP had a compens

  12. Purification and use of E. coli peptide deformylase for peptide deprotection in chemoenzymatic peptide synthesis

    NARCIS (Netherlands)

    Di Toma, Claudia; Sonke, Theo; Quaedflieg, Peter J.; Janssen, Dick B.

    2013-01-01

    Peptide deformylases (PDFs) catalyze the removal of the formyl group from the N-terminal methionine residue in nascent polypeptide chains in prokaryotes. Its deformylation activity makes PDF an attractive candidate for the biocatalytic deprotection of formylated peptides that are used in chemoenzyma

  13. The vasorelaxant effect of adrenomedullin, proadrenomedullin N-terminal 20 peptide and amylin in human skin

    DEFF Research Database (Denmark)

    Hasbak, Philip; Eskesen, Karen; Lind, Peter Henrik

    2006-01-01

    In this study we aimed to assess in vivo, the vasodilator effects of adrenomedullin, proadrenomedullin N-terminal 20 peptide (PAMP) and amylin in human skin vasculature and compare the responses to the effects mediated by the endogenous neuropeptides calcitonin gene-related peptide (CGRP......) and substance P and to examine the mRNA expression of calcitonin receptor-like receptor (CL-R) and receptor-activity modifying proteins, RAMP1, RAMP 2 and RAMP3 in human subcutaneous arteries. Changes in skin blood flow of the forearm were measured using a Laser Doppler Imager after intradermal injection...... of CGRP, adrenomedullin and amylin induces long lasting dilatation of human skin vasculature by activation of CGRP1 receptors. PAMP induces transient vasodilatation. PAMP but not CGRP, adrenomedullin and amylin causes itch sensation and local erythema. The transient effect on vasodilatation as response...

  14. Development, characterization, and epitope mapping of a panel of twenty-four monoclonal antibodies specific for human inducible nitric oxide synthase.

    Science.gov (United States)

    Webber, Robert J; Rodriguez, John G; Webber, Douglas S; Dunnebacke, Thelma H

    2005-02-01

    A panel of monoclonal antibodies (MAbs) to human inducible nitric oxide synthase (hiNOS) has been developed. By isotype analysis of the MAbs cloned from the 24 different positive hybridomas, 13 were determined to be mouse IgG1, two were mouse IgG2a, two were mouse IgG2b, and the seven others were mouse IgM antibodies: all contained kappa light chains. The anti-hiNOS MAbs were initially characterized by ELISA, RIA, Western blot, and immunocytochemistry, and then they were epitope mapped using synthetic peptides and a three-step mapping procedure. In the first step, each of the 24 MAbs was tested by indirect ELISA for binding to 96 overlapping 18-amino acid-long peptides that span the entire 1153-amino acid length of hiNOS. Eight IgG class anti-hiNOS MAbs were found to bind to one of five different peptides. In the second step, a series of amino terminal and carboxyl terminal truncated peptides were synthesized for each of the five peptides to which one or more of the MAbs bound. Each of the eight anti-hiNOS MAbs was found to bind to the truncated peptides with a unique specificity that identified the amino acid segment involved in binding. The third step in the epitope mapping process utilized three series of overlapping 5-, 6-, 7-, 8-, and 9-amino acid-long peptides for each of these segments and identified the exact amino acids of hiNOS involved in antibody binding. Anti-hiNOS MAbs 2A1-F8, 2D2-B2, 21C10-1D10, and 24B10-2C7 were found to be especially useful in different immunoassays.

  15. Transcriptomic analysis of a tertiary relict plant, extreme xerophyte Reaumuria soongorica to identify genes related to drought adaptation.

    Directory of Open Access Journals (Sweden)

    Yong Shi

    Full Text Available BACKGROUND: Reaumuria soongorica is an extreme xerophyte shrub widely distributed in the desert regions including sand dune, Gobi and marginal loess of central Asia which plays a crucial role to sustain and restore fragile desert ecosystems. However, due to the lacking of the genomic sequences, studies on R. soongorica had mainly limited in physiological responses to drought stress. Here, a deep transcriptomic sequencing of R. soongorica will facilitate molecular functional studies and pave the path to understand drought adaptation for a desert plant. METHODOLOGY/PRINCIPAL FINDINGS: A total of 53,193,660 clean paired-end reads was generated from the Illumina HiSeq™ 2000 platform. By assembly with Trinity, we got 173,700 contigs and 77,647 unigenes with mean length of 677 bp and N50 of 1109 bp. Over 55% (43,054 unigenes were successfully annotated based on sequence similarity against public databases as well as Rfam and Pfam database. Local BLAST and Kyoto Encyclopedia of Genes and Genomes (KEGG maps were used to further exhausting seek for candidate genes related to drought adaptation and a set of 123 putative candidate genes were identified. Moreover, all the C4 photosynthesis genes existed and were active in R. soongorica, which has been regarded as a typical C3 plant. CONCLUSION/SIGNIFICANCE: The assembled unigenes in present work provide abundant genomic information for the functional assignments in an extreme xerophyte R. soongorica, and will help us exploit the genetic basis of how desert plants adapt to drought environment in the near future.

  16. The Source of Genes Related to Rice Grain Starch Synthesis Among Cultivated Varieties and Its Contribution to Quality

    Institute of Scientific and Technical Information of China (English)

    YAN Chang-jie; TIAN Shun; ZHANG Zheng-qiu; HAN Yue-peng; CHEN Feng; LI Xin; GU Ming-hong

    2007-01-01

    The property of starch in rice grain endosperm is a very important determinant for rice quality, and it is essential to understand the genetic effect of the genes related to starch synthesis in high-yielding rice varieties for rice quality improvement. The physicochemical properties (e.g., amylose content, gel consistency, and RVA profile) were assessed on 53 rice varieties, including certain typical indica/japonica landraces and certain high-yielding modern varieties. And molecular markers for Sbel, Sbe3 developed on the basis of sequence diversities between the rice subspecies indica and japonica, together with PCR-Acc Ⅰ marker for Wx gene were used to investigate the genotypes of 53 rice cultivars. The result showed that the developed molecular markers for Wx, Sbel, Sbe3 could distinguish indica or japonica alleles at three loci. Among all the 53 rice cultivars, six genotypes were observed when Sbel, Sbe3, and Wx loci were considered together, while the genotypes of WxiSbeljSbe3i and WxiSbeljSbe3j were absent. In order to explore the genetic effects of the three genes, especially for starch branching enzyme genes, ANOVA and multiple comparison analysis were conducted.The results showed that rice cultivars with different genotypes exhibited different phenotypes, including amylose content,gel consistency and certain RVA characteristics, and the significant differences among the six genotypes were observed.It was concluded that these three genes had randomly recombined during the process of the rice variety development.And the genetic effects of indica and japonica alleles at three gene loci were different, of which, Wx gene plays a major role in determining the starch properties, followed by Sbel and Sbe3, and the genetic effects of Sbel and Sbe3 in different backgrounds (Wxi, Wxj) are different. The results have provided a clue for rice good quality variety development, and the molecular markers will benefit to the improvement in quality of rice.

  17. Screening of genes related to ovarian development in the swimming crab, Portunus trituberculatus, by suppression subtractive hybridization.

    Science.gov (United States)

    Yu, Z B; Mu, C K; Song, W W; Li, R H; Chen, Y E; Wang, C L

    2015-12-29

    The swimming crab, Portunus trituberculatus, is an important marine animal and is widely cultured in China. In the present study, suppression subtractive hybridization was applied to identify the differentially expressed genes in the ovaries of mature and immature P. trituberculatus. One hundred and seventy six expressed sequence tag (ESTs) were identified, of which 100 were down-regulated, and 76 up-regulated. BLAST analysis identified 51 unigenes, of which 27 were down-regulated, and 24 up-regulated. Quantitative real-time reverse transcriptase polymerase chain reaction results indicated that the SSH technique is valuable in screening genes related to ovarian development. Genes identified in this study encoded proteins corresponding to a wide range of functions and included immune response protein, transcription initiation factor, metabolic proteins, chromosome, histone h3, ovarian development-related protein, and vitellogenin. In addition, 64 metabolic pathways were annotated in differentially expressed ESTs by using the Kyoto Encyclopedia of Genes and Genomes pathway. Four annotated pathways (oxidative phosphorylation, carbon metabolism, fatty acid degradation, and protein digestion and absorption) appeared to be involved in ovarian development. In ontology analysis, 5.83% of the cellular process genes in reverse subtraction cDNA library are involved in reproduction, and 5.88% involved in developmental process. In up-regulated genes, myosin II-expressed polehole-like protein; histone h3; ovigerous-hair stripping substance; peritrophin 48; and ovarian development-related protein appeared to be involved in ovarian development. Identification of differentially expressed genes in the mature and immature ovary of the swimming crab provides new insights for further studies on the mechanism underlying ovarian development in this species.

  18. Screening the Drug Sensitivity Genes Related to GEM and CDDP in the Lung Cancer Cell-lines

    Directory of Open Access Journals (Sweden)

    Chunyu YANG

    2009-10-01

    Full Text Available Background and objective Screening of small-cell lung cancer (SCLC and non-small cell lung cancer (NSCLC cell lines with gemcitabine hydrochloride (GEM and cisplatin (CDDP related to drug sensitivity gene might clarify the action mechanism of anti-cancer drugs and provide a new clue for overcoming drug resistance and the development of new anti-cancer drugs, and also provide theoretical basis for the clinical treatment of individual. Methods The drug sensitivity of CDDP and GEM in 4 SCLC cell lines and 6 NSCLC cell lines was determined using MTT colorimetric assay, while the cDNA macroarray was applied to detect the gene expression state related to drug sensitivity of 10 lung cancer cell line in 1 291, and the correlation between the two was analysized. Results There were 6 genes showing significant positive correlation (r≥0.632, P < 0.05 with GEM sensitivity; 45 genes positively related to CDDP; another 41 genes related to both GEM and CDDP (r≥± 0.4. Lung cancer with GEM and CDDP sensitivity of two types of drugs significantly related genes were Metallothinein (Signal transduction molecules, Cathepsin B (Organization protease B and TIMP1 (Growth factor; the GEM, CDDP sensitivity associated genes of lung cancer cell lines mainly distributed in Metallothinein, Cathepsin B, growth factor TIMP1 categories. Conclusion There existed drug-related sensitive genes of GEM, CDDP in SCLC and NSCLC cell lines; of these genes, Metallothinein, Cathepsin B and TIMP1 genes presented a significant positive correlation with GEM drug sensitivity, a significant negative correlation with CDDP drug sensitivity.

  19. Protective effects of Lingguizhugan decoction on amyloid-beta peptide (25-35)-induced cell injury Anti-inflammatory effects

    Institute of Scientific and Technical Information of China (English)

    Feifei Xi; Feng Sang; Chunxiang Zhou; Yun Ling

    2012-01-01

    In the present study, a human neuroblastoma cell line (SH-SY5Y) and BV-2 microglia were treated with amyloid-β peptide (25-35), as a model of Alzheimer's disease, to evaluate the protective effects of 10-3-10-8 g/mL Lingguizhugan decoction and to examine the underlying anti-inflammatory mechanism. Lingguizhugan decoction significantly enhanced the viability of SH-SY5Y cells with amyloid-β peptide-induced injury, and lowered levels of interleukin-1β, interleukin-6, tumor necrosis factor-α and nitric oxide in the culture supernatant of activated BV-2 microglia. The effects of 10-3 g/mL Lingguizhugan decoction were more significant. These results suggest that Lingguizhugan decoction can protect SH-SY5Y cells against amyloid-β peptide (25-35)-induced injury in a dose-dependent manner by inhibiting overexpression of inflammatory factors by activated microglia.

  20. Potential of phage-displayed peptide library technology to identify functional targeting peptides

    Science.gov (United States)

    Krumpe, Lauren RH; Mori, Toshiyuki

    2010-01-01

    Combinatorial peptide library technology is a valuable resource for drug discovery and development. Several peptide drugs developed through phage-displayed peptide library technology are presently in clinical trials and the authors envision that phage-displayed peptide library technology will assist in the discovery and development of many more. This review attempts to compile and summarize recent literature on targeting peptides developed through peptide library technology, with special emphasis on novel peptides with targeting capacity evaluated in vivo. PMID:20150977

  1. Radiopharmaceutical development of radiolabelled peptides

    Energy Technology Data Exchange (ETDEWEB)

    Fani, Melpomeni; Maecke, Helmut R. [University Hospital Freiburg, Department of Nuclear Medicine, Freiburg (Germany)

    2012-02-15

    Receptor targeting with radiolabelled peptides has become very important in nuclear medicine and oncology in the past few years. The overexpression of many peptide receptors in numerous cancers, compared to their relatively low density in physiological organs, represents the molecular basis for in vivo imaging and targeted radionuclide therapy with radiolabelled peptide-based probes. The prototypes are analogs of somatostatin which are routinely used in the clinic. More recent developments include somatostatin analogs with a broader receptor subtype profile or with antagonistic properties. Many other peptide families such as bombesin, cholecystokinin/gastrin, glucagon-like peptide-1 (GLP-1)/exendin, arginine-glycine-aspartic acid (RGD) etc. have been explored during the last few years and quite a number of potential radiolabelled probes have been derived from them. On the other hand, a variety of strategies and optimized protocols for efficient labelling of peptides with clinically relevant radionuclides such as {sup 99m}Tc, M{sup 3+} radiometals ({sup 111}In, {sup 86/90}Y, {sup 177}Lu, {sup 67/68}Ga), {sup 64/67}Cu, {sup 18}F or radioisotopes of iodine have been developed. The labelling approaches include direct labelling, the use of bifunctional chelators or prosthetic groups. The choice of the labelling approach is driven by the nature and the chemical properties of the radionuclide. Additionally, chemical strategies, including modification of the amino acid sequence and introduction of linkers/spacers with different characteristics, have been explored for the improvement of the overall performance of the radiopeptides, e.g. metabolic stability and pharmacokinetics. Herein, we discuss the development of peptides as radiopharmaceuticals starting from the choice of the labelling method and the conditions to the design and optimization of the peptide probe, as well as some recent developments, focusing on a selected list of peptide families, including somatostatin

  2. A heptameric peptide purified from Spirulina sp. gastrointestinal hydrolysate inhibits angiotensin I-converting enzyme- and angiotensin II-induced vascular dysfunction in human endothelial cells.

    Science.gov (United States)

    Heo, Seong-Yeong; Ko, Seok-Chun; Kim, Chang Su; Oh, Gun-Woo; Ryu, Bomi; Qian, Zhong-Ji; Kim, Geunhyung; Park, Won Sun; Choi, Il-Whan; Phan, Thi Tuong Vy; Heo, Soo-Jin; Kang, Do-Hyung; Yi, Myunggi; Jung, Won-Kyo

    2017-05-01

    In this study, a marine microalga Spirulina sp.-derived protein was hydrolyzed using gastrointestinal enzymes to produce an angiotensin I (Ang I)-converting enzyme (ACE) inhibitory peptide. Following consecutive purification, the potent ACE inhibitory peptide was composed of 7 amino acids, Thr-Met‑Glu‑Pro‑Gly‑Lys-Pro (molecular weight, 759 Da). Analysis using the Lineweaver-Burk plot and molecular modeling suggested that the purified peptide acted as a mixed non-competitive inhibitor of ACE. The inhibitory effects of the peptide against the cellular production of vascular dysfunction-related factors induced by Ang II were also investigated. In human endothelial cells, the Ang II-induced production of nitric oxide and reactive oxygen species was inhibited, and the expression of inducible nitric oxide synthase (iNOS) and endothelin-1 (ET-1) was downregulated when the cells were cultured with the purified peptide. Moreover, the peptide blocked the activation of p38 mitogen‑activated protein kinase. These results indicated that this Spirulina sp.-derived peptide warrants further investigation as a potential pharmacological inhibitor of ACE and vascular dysfunction.

  3. Nitric oxide as a carcinogen. Analysis by yeast functional assay of inactivating p53 mutations induced by nitric oxide

    Energy Technology Data Exchange (ETDEWEB)

    Murata, Jun-Ichi; Tada, Mitsuhiro; Sawamura, Yutaka; Shinohe, Yumiko; Abe, Hiroshi [Laboratory for Molecular Brain Research, Department of Neurosurgery, Hokkaido University School of Medicine, Sapporo (Japan); Iggo, Richard D. [Oncogene group, Swiss Institute for Experimental Cancer Research ISREC, Epalinges (Switzerland)

    1997-10-06

    We have used a yeast p53 functional assay to study induction of mutations in the p53 tumor suppressor gene by nitric oxide and cytosine methylation. The yeast assay identifies only biologically important p53 mutations. p53 cDNA was treated with the nitric oxide donor sydnonimine, PCR-amplified and transfected into yeast. Sydnonimine produced a significant, dose-dependent increase in C:G->A:T transversions. Many important p53 mutational hotspots are postulated to arise by deamination of methylCpG in tumors. We therefore examined nitric oxide induction of mutations in p53 cDNA methylated by PCR-mediated substitution of 5-methylcytosine for cytosine or by treatment with the SssI CpG methylase. Both methylation procedures increased the baseline mutation rate, and nitric oxide treatment produced a further increase in mutation yield. Sequence analysis showed that methylation alone led to C:G->T:A transitions, whereas nitric oxide treatment simply produced more C:G->A:T transversions. Thus the most important factor in C:G->T:A transition at CpG sites identified in this experimental system is cytosine methylation, consistent with spontaneous conversion of 5-methylcytosine to thymine by deamination

  4. Pain modulation by nitric oxide in the spinal cord.

    Directory of Open Access Journals (Sweden)

    Marco Aurelio M Freire

    2009-09-01

    Full Text Available Nitric oxide (NO is a versatile messenger molecule first associated with endothelial relaxing effects. In the central nervous system (CNS, NO synthesis is primarily triggered by activation of N-methyl-D-aspartate (NMDA receptors and has a Janus face, with both beneficial and harmful properties, depending on concentration and the identity of its synthetic enzyme isoform. There are three isoforms of the NO synthesizing enzyme nitric oxide synthase (NOS: neuronal (nNOS, endothelial (eNOS, and inducible nitric oxide synthase (iNOS, each one involved with specific events in the brain. In CNS, nNOS is involved with modulation of synaptic transmission through long-term potentiation in several regions, including nociceptive circuits in the spinal cord. Here, we review the role played by NO on central pain sensitization.

  5. A nitric oxide donor (nitroglycerin) triggers genuine migraine attacks

    DEFF Research Database (Denmark)

    Thomsen, L L; Kruuse, C; Iversen, Helle Klingenberg

    1994-01-01

    Supersensitivity to induction of headache and arterial dilatation by a donor of nitric oxide (nitroglycerin) has recently been demonstrated in migraine sufferers. The aims of the present study were to examine whether the nitric oxide donor nitroglycerin may induce a typical migraine attack.......03). The time pattern of headache and estimated middle cerebral artery dilatation corresponded well. The study therefore demonstrates that activation of the nitric oxide cGMP pathway may cause typical migraine attacks......., to exclude placebo-related effects and to describe the relation between middle cerebral artery dilatation and provoked migraine. Nitroglycerin (0.5 μg/kg/min for 20 min) or placebo was infused into 12 migraine patients in a double-blind cross-over trial. Blood velocity in the middle cerebral artery...

  6. Photochemical reactions of neptunium in nitric acid solution containing photocatalyst

    Energy Technology Data Exchange (ETDEWEB)

    Fukasawa, Tetsuo; Kawamura, Fumio (Hitachi Ltd., Ibaraki (Japan). Energy Research Lab.)

    1991-01-01

    Photochemical oxidation and reduction behaviors of neptunium were preliminarily investigated in 3 mol/l nitric acid solution. Nitric acid of 3 mol/l simulated the high level waste solution from a spent fuel reprocessing process. Concentrations of Np(V), Np(VI) and nitrous acid were determined with a photospectrometer, and solution potential with an electrode. Without additives, Np(VI) was reduced to Np(V) by nitrous acid which was photolytically generated from nitric acid. With a scavenger for nitrous acid, Np(V) was oxidized to extractable Np(VI) by a photolytically generated oxidizing reagent which were predicted by the solution potential measurement. The reduction rate was higher than the oxidation rate because of the larger quantity and higher reactivity of nitrous acid than an oxidizing reagent. Photocatalyst was proved to be effective for the oxidation of Np(V) to Np(VI). (author).

  7. Nitric oxide: an intermediate in nitrate reduction in Klebsiella pneumoniae

    Energy Technology Data Exchange (ETDEWEB)

    Al-Abdulla, J.M.; Aleem, M.I.H.

    1977-01-01

    When K. pneumoniae cells were grown anaerobically with nitrate as the final electron acceptor, there was a rapid reduction of nitrate to nitrite. The latter was further reduced to hydroxylamine and finally to ammonia. Nitrate, nitrite and nitric oxide, but not nitrous oxide, could accept electrons from the respiratory chain. During growth of the organism it was possible to trap nitric oxide with alkaline permanganate. The trapped gas represented only a small portion of the reduced electron acceptor. It would appear that a major portion of nitric oxide produced from nitrite reduction must be converted to an unknown nitrogenous intermediate with an oxidation state of +1 before its reduction to hydroxylamine. The possible nature of this elusive intermediate should be discussed.

  8. Nitric Oxide in Astrocyte-Neuron Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Li, Nianzhen [Iowa State Univ., Ames, IA (United States)

    2002-01-01

    Astrocytes, a subtype of glial cell, have recently been shown to exhibit Ca2+ elevations in response to neurotransmitters. A Ca2+ elevation can propagate to adjacent astrocytes as a Ca2+ wave, which allows an astrocyte to communicate with its neighbors. Additionally, glutamate can be released from astrocytes via a Ca2+-dependent mechanism, thus modulating neuronal activity and synaptic transmission. In this dissertation, the author investigated the roles of another endogenous signal, nitric oxide (NO), in astrocyte-neuron signaling. First the author tested if NO is generated during astrocytic Ca2+ signaling by imaging NO in purified murine cortical astrocyte cultures. Physiological concentrations of a natural messenger, ATP, caused a Ca2+-dependent NO production. To test the roles of NO in astrocytic Ca2+ signaling, the author applied NO to astrocyte cultures via addition of a NO donor, S-nitrosol-N-acetylpenicillamine (SNAP). NO induced an influx of external Ca2+, possibly through store-operated Ca2+ channels. The NO-induced Ca2+ signaling is cGMP-independent since 8-Br-cGMP, an agonistic analog of cGMP, did not induce a detectable Ca2+ change. The consequence of this NO-induced Ca2+ influx was assessed by simultaneously monitoring of cytosolic and internal store Ca2+ using fluorescent Ca2+ indicators x-rhod-1 and mag-fluo-4. Blockage of NO signaling with the NO scavenger PTIO significantly reduced the refilling percentage of internal stores following ATP-induced Ca2+ release, suggesting that NO modulates internal store refilling. Furthermore, locally photo-release of NO to a single astrocyte led to a Ca2+ elevation in the stimulated astrocyte and a subsequent Ca2+ wave to neighbors. Finally, the author tested the role of NO inglutamate-mediated astrocyte-neuron signaling by

  9. Nitric Oxide in Astrocyte-Neuron Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Nianzhen Li

    2002-06-27

    Astrocytes, a subtype of glial cell, have recently been shown to exhibit Ca{sup 2+} elevations in response to neurotransmitters. A Ca{sup 2+} elevation can propagate to adjacent astrocytes as a Ca{sup 2+} wave, which allows an astrocyte to communicate with its neighbors. Additionally, glutamate can be released from astrocytes via a Ca{sup 2+}-dependent mechanism, thus modulating neuronal activity and synaptic transmission. In this dissertation, the author investigated the roles of another endogenous signal, nitric oxide (NO), in astrocyte-neuron signaling. First the author tested if NO is generated during astrocytic Ca{sup 2+} signaling by imaging NO in purified murine cortical astrocyte cultures. Physiological concentrations of a natural messenger, ATP, caused a Ca{sup 2+}-dependent NO production. To test the roles of NO in astrocytic Ca{sup 2+} signaling, the author applied NO to astrocyte cultures via addition of a NO donor, S-nitrosol-N-acetylpenicillamine (SNAP). NO induced an influx of external Ca{sup 2+}, possibly through store-operated Ca{sup 2+} channels. The NO-induced Ca{sup 2+} signaling is cGMP-independent since 8-Br-cGMP, an agonistic analog of cGMP, did not induce a detectable Ca{sup 2+} change. The consequence of this NO-induced Ca{sup 2+} influx was assessed by simultaneously monitoring of cytosolic and internal store Ca{sup 2+} using fluorescent Ca{sup 2+} indicators x-rhod-1 and mag-fluo-4. Blockage of NO signaling with the NO scavenger PTIO significantly reduced the refilling percentage of internal stores following ATP-induced Ca{sup 2+} release, suggesting that NO modulates internal store refilling. Furthermore, locally photo-release of NO to a single astrocyte led to a Ca{sup 2+} elevation in the stimulated astrocyte and a subsequent Ca{sup 2+} wave to neighbors. Finally, the author tested the role of NO inglutamate-mediated astrocyte-neuron signaling by recording the astrocyte-evoked glutamate-dependent neuronal slow inward current (SIC

  10. Light activated nitric oxide releasing materials

    Science.gov (United States)

    Muizzi Casanas, Dayana Andreina

    The ability to control the location and dosage of biologically active molecules inside the human body can be critical to maximizing effective treatment of cardiovascular diseases like angina. The current standard of treatment relies on the metabolism of organonitrate drugs into nitric oxide (NO), which are not specific, and also show problems with densitization with long-term use. There is a need then to create a treatment method that gives targeted release of NO. Metal-nitrosyl (M-NO) complexes can be used for delivery of NO since the release of NO can be controlled with light. However, the NO-releasing drug must be activated with red light to ensure maximum penetration of light through tissue. However, the release of NO from M-NO complexes with red-light activation is a significant challenge since the energy required to break the metal-NO bond is usually larger than the energy provided by red light. The goal of this project was to create red- sensitive, NO-releasing materials based on Ru-salen-nitrosyl compounds. Our approach was to first modify Ru salen complexes to sensitize the photochemistry for release of NO after red light irradiation. Next, we pursued polymerization of the Ru-salen complexes. We report the synthesis and quantitative photochemical characterization of a series of ruthenium salen nitrosyl complexes. These complexes were modified by incorporating electron donating groups in the salen ligand structure at key locations to increase electron density on the Ru. Complexes with either an --OH or --OCH3 substituent showed an improvement in the quantum yield of release of NO upon blue light irradiation compared to the unmodified salen. These --OH and --OCH3 complexes were also sensitized for NO release after red light activation, however the red-sensitive complexes were unstable and showed ligand substitution on the order of minutes. The substituted complexes remained sensitive for NO release, but only after blue light irradiation. The Ru

  11. New vasoactive peptides in cirrhosis

    DEFF Research Database (Denmark)

    Kimer, Nina; Goetze, Jens Peter; Bendtsen, Flemming;

    2014-01-01

    BACKGROUND: Patients with cirrhosis have substantial circulatory imbalance between vasoconstrictive and vasodilating forces. The study of circulatory vasoactive peptides may provide important pathophysiological information. This study aimed to assess concentrations, organ extraction and relations...... to haemodynamic changes in the pro-peptides copeptin, proadrenomedullin and pro-atrial natriuretic peptide (proANP) in patients with cirrhosis. MATERIALS AND METHODS: Fifty-four cirrhotic patients and 15 controls were characterized haemodynamically during a liver vein catheterization. Copeptin, proadrenomedullin...... found no extraction of copeptin, proadrenomedullin or proANP over the liver. Copeptin correlated with portal pressure (R=0·50, P

  12. Next generation natriuretic peptide measurement

    DEFF Research Database (Denmark)

    Hunter, Ingrid; Goetze, Jens P

    2012-01-01

    Plasma measurement of natriuretic peptides is a "must" for clinical laboratories. For the next generation measurement, the unraveling of the molecular complexity of the peptides points toward a more qualitative assessment, as the posttranslational processing also changes with disease. Changes...... in the molecular heterogeneity could in itself contain valuable information of clinical status, and the time seems right for industry and dedicated researchers in the field to get together and discuss the next generation natriuretic peptide measurement. In such an environment, new strategies can be developed...

  13. Peptide primary messengers in plants

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The peptide primary messengers regulate embryonic development,cell growth and many other activities in animal cells. But recent evidence verified that peptide primary messengers are also involved in plant defense responses, the recognition between pollen and stigma and keep the balance between cell proliferation and differentiations in shoot apical meristems. Those results suggest that plants may actually make wide use of peptide primary messengers, both in embryonic development and late life when they rally their cells to defend against pathogens and insect pests. The recent advance in those aspects is reviewed.

  14. Targeting the Eph System with Peptides and Peptide Conjugates.

    Science.gov (United States)

    Riedl, Stefan J; Pasquale, Elena B

    2015-01-01

    Eph receptor tyrosine kinases and ephrin ligands constitute an important cell communication system that controls development, tissue homeostasis and many pathological processes. Various Eph receptors/ephrins are present in essentially all cell types and their expression is often dysregulated by injury and disease. Thus, the 14 Eph receptors are attracting increasing attention as a major class of potential drug targets. In particular, agents that bind to the extracellular ephrin-binding pocket of these receptors show promise for medical applications. This pocket comprises a broad and shallow groove surrounded by several flexible loops, which makes peptides particularly suitable to target it with high affinity and selectivity. Accordingly, a number of peptides that bind to Eph receptors with micromolar affinity have been identified using phage display and other approaches. These peptides are generally antagonists that inhibit ephrin binding and Eph receptor/ ephrin signaling, but some are agonists mimicking ephrin-induced Eph receptor activation. Importantly, some of the peptides are exquisitely selective for single Eph receptors. Most identified peptides are linear, but recently the considerable advantages of cyclic scaffolds have been recognized, particularly in light of potential optimization towards drug leads. To date, peptide improvements have yielded derivatives with low nanomolar Eph receptor binding affinity, high resistance to plasma proteases and/or long in vivo half-life, exemplifying the merits of peptides for Eph receptor targeting. Besides their modulation of Eph receptor/ephrin function, peptides can also serve to deliver conjugated imaging and therapeutic agents or various types of nanoparticles to tumors and other diseased tissues presenting target Eph receptors.

  15. Thyroid disorders and nitric oxide in cardiovascular adaptation to hypovolemia.

    Science.gov (United States)

    Ogonowski, Natalia; Piro, Giselle; Pessah, Déborah; Arreche, Noelia; Puchulu, Bernardita; Balaszczuk, Ana M; Fellet, Andrea L

    2016-08-01

    This study aimed to investigate whether nitric oxide participates in the cardiovascular function and haemodynamic adaptation to acute haemorrhage in animals with thyroid disorders. Sprague-Dawley rats aged 2months old treated with T3 (hyper, 20μg/100g body weight) or 0.02% methimazole (hypo, w/v) during 28days were pre-treated with N(G) nitro-l-arginine methyl ester (L-NAME) and submitted to 20% blood loss. Heart function was evaluated by echocardiography. Measurements of arterial blood pressure, heart rate, nitric oxide synthase activity and protein levels were performed. We found that hypo decreased fractional shortening and ejection fraction and increased left ventricle internal diameter. Hyper decreased ventricle diameter and no changes in cardiac contractility. Haemorrhage elicited a hypotension of similar magnitude within 10min. Then, this parameter was stabilized at about 30-40min and maintained until finalized, 120min. L-NAME rats showed that the immediate hypotension would be independent of nitric oxide. Nitric oxide synthase inhibition blunted the changes of heart rate induced by blood loss. Hyper and hypo had lower atrial enzyme activity associated with a decreased enzyme isoform in hypo. In ventricle, hyper and hypo had a higher enzyme activity, which was not correlated with changes in protein levels. Haemorrhage induced an increased heart nitric oxide production. We concluded that thyroid disorders were associated with hypertrophic remodelling which impacted differently on cardiac function and its adaptation to a hypovolemia. Hypovolemia triggered a nitric oxide synthase activation modulating the heart function to maintain haemodynamic homeostasis. This involvement depends on a specific enzyme isoform, cardiac chamber and thyroid state.

  16. Hippocampal neuronal nitric oxide synthase mediates the stress-related depressive behaviors of glucocorticoids by downregulating glucocorticoid receptor.

    Science.gov (United States)

    Zhou, Qi-Gang; Zhu, Li-Juan; Chen, Chen; Wu, Hai-Yin; Luo, Chun-Xia; Chang, Lei; Zhu, Dong-Ya

    2011-05-25

    The molecular mechanisms underlying the behavioral effects of glucocorticoids are poorly understood. We report here that hippocampal neuronal nitric oxide synthase (nNOS) is a crucial mediator. Chronic mild stress and glucocorticoids exposures caused hippocampal nNOS overexpression via activating mineralocorticoid receptor. In turn, hippocampal nNOS-derived nitric oxide (NO) significantly downregulated local glucocorticoid receptor expression through both soluble guanylate cyclase (sGC)/cGMP and peroxynitrite (ONOO(-))/extracellular signal-regulated kinase signal pathways, and therefore elevated hypothalamic corticotrophin-releasing factor, a peptide that governs the hypothalamic-pituitary-adrenal axis. More importantly, nNOS deletion or intrahippocampal nNOS inhibition and NO-cGMP signaling blockade (using NO scavenger or sGC inhibitor) prevented the corticosterone-induced behavioral modifications, suggesting that hippocampal nNOS is necessary for the role of glucocorticoids in mediating depressive behaviors. In addition, directly delivering ONOO(-) donor into hippocampus caused depressive-like behaviors. Our findings reveal a role of hippocampal nNOS in regulating the behavioral effects of glucocorticoids.

  17. Screening of TACE Peptide Inhibitors from Phage Display Peptide Library

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To obtain the recombinant tumor necrosis factor-α converting enzyme (TACE) ectodomain and use it as a selective molecule for the screening of TACE peptide inhibitors, the cDNA coding catalytic domain (T800) and full-length ectodomain (T1300) of TACE were amplified by RTPCR, and the expression plasmids were constructed by inserting T800 and T1300 into plasmid pET28a and pET-28c respectively. The recombinant T800 and T1300 were induced by IPTG, and SDSPAGE and Western blotting analysis results revealed that T800 and T1300 were highly expressed in the form of inclusion body. After Ni2+-NTA resin affinity chromatography, the recombinant proteins were used in the screening of TACE-binding peptides from phage display peptide library respectively. After 4 rounds of biopanning, the positive phage clones were analyzed by ELISA, competitive inhibition assay and DNA sequencing. A common amino acid sequence (TRWLVYFSRPYLVAT) was found and synthesized. The synthetic peptide could inhibit the TNF-α release from LPS-stimulated human peripheral blood mononuclear cells (PBMC) up to 60.3 %. FACS analysis revealed that the peptide mediated the accumulation of TNF-α on the cell surface. These results demonstrate that the TACE-binding peptide is an effective antagonist of TACE.

  18. EFFECTS OF CERTAIN VASOACTIVE PEPTIDES ON PATHOGENESIS OF VASCULAR RESTENOSIS

    Institute of Scientific and Technical Information of China (English)

    刘乃奎; 陈光慧; 王晓红; 姚兴海; 苏加林; 李田昌; 武旭东; 张勇刚; 汤健; 唐朝枢

    2003-01-01

    Objective.To investigate the effects of several vasoactive peptides on the development of arterial restenosis after balloon angioplasty. Methods. In rat aortic artery restenosis model produced by denudation of aortic endothelia,we observed changes of endothelin(ET),angiotensin II(AII),calcitonin gene-related peptide(CGRP)and adrenomedullin(Adm)in plasma and aorta with radioimmunoassay and expression of hypertension-related gene(HRG-1)with semi-quantitative RT-PCR,and studied the effects of these peptides on intimal hyperplasia,intima/media ratio and MAPK activities of aortic artery after angioplasty respectively. Furthermore,in cultured cells,we studied the effects of these peptides on vascular smooth muscle cell(VSMC) proliferation and expression of HRG-1 of VSMC from spontaneously hypertensive rats(SHR)and Wistar-Kyoto(WKY)rats with 3H-TdR incorporation and RT-PCR respectively. Results. After angioplasty,the levels of ET and AII in plasma and aorta significantly increased,accompanied with VSMC proliferation and neointima hyperplasia. On day 10 after angioplasty,the levels of ET in plasma and aorta increased by 69% and 124% respectively,compared with sham group(P<0.01);and the level of aortic AII increased by 80%(P< 0.01). Antiserum against ET or inhibitors of angiotensin converting enzyme(ACE)could significantly inhibit the proliferation of VSMC and neointima formation. Compared with the sham group,on day 3 after angioplasty,the CGRP levels in plasma and aorta increased by 64% and 89% respectively(P< 0.01)and the Adm levels in plasma and tissue increased by 129% and 102% respectively(P< 0.01). On day 10,intravenous administration of CGRP significantly inhibited the proliferation of VSMC and neointima forma-tion induced by balloon aortic injury(by 66% and 79% respectively,P< 0.01). In addition,ET and AII attenuated the expression of HRG-1 in aorta and stimulated mitogen-activated protein kinase(MAPK)activity,while CGRP and Adm potentiated the expression of HRG-1

  19. Exhaled nitric oxide in 4-year-old children : relationship with asthma and atopy

    NARCIS (Netherlands)

    Brussee, JE; Smit, HA; Kerkhof, M; Koopman, LP; Wijga, AH; Postma, DS; Gerritsen, J; Grobee, DE; Brunekreef, B; De Jongste, JC

    Airway inflammation is an early feature of asthma. Early detection and antiinflammatory treatment may have important therapeutic impact. Exhaled nitric oxide is a noninvasive marker of airway inflammation. The current study investigated the association between exhaled nitric oxide and asthma,

  20. Exhaled nitric oxide in 4-year-old children: relationship with asthma and atopy

    NARCIS (Netherlands)

    Brussee, J.E.; Smit, H.A.; Kerkhof, M.; Koopman, L.P.; Wijga, A.H.; Postma, D.S.; Gerritsen, J.; Grobbee, D.E.; Brunekreef, B.; Jongste, J.C. de

    2005-01-01

    Airway inflammation is an early feature of asthma. Early detection and antiinflammatory treatment may have important therapeutic impact. Exhaled nitric oxide is a noninvasive marker of airway inflammation. The current study investigated the association between exhaled nitric oxide and asthma,

  1. Elevated exhaled nitric oxide in high-risk neonates precedes transient early but not persistent wheeze

    DEFF Research Database (Denmark)

    Chawes, Bo L K; Buchvald, Frederik; Bischoff, Anne Louise;

    2010-01-01

    Elevated fractional exhaled nitric oxide (Fe(NO)) concentration has been suggested to predict early childhood wheeze and sensitization.......Elevated fractional exhaled nitric oxide (Fe(NO)) concentration has been suggested to predict early childhood wheeze and sensitization....

  2. Mitochondrial N-formyl peptides induce cardiovascular collapse and sepsis-like syndrome.

    Science.gov (United States)

    Wenceslau, Camilla Ferreira; McCarthy, Cameron G; Szasz, Theodora; Goulopoulou, Styliani; Webb, R Clinton

    2015-04-01

    Fifty percent of trauma patients who present sepsis-like syndrome do not have bacterial infections. This condition is known as systemic inflammatory response syndrome (SIRS). A unifying factor of SIRS and sepsis is cardiovascular collapse. Trauma and severe blood loss cause the release of endogenous molecules known as damage-associated molecular patterns. Mitochondrial N-formyl peptides (F-MIT) are damage-associated molecular patterns that share similarities with bacterial N-formylated peptides and are potent immune system activators. The goal of this study was to investigate whether F-MIT trigger SIRS, including hypotension and vascular collapse via formyl peptide receptor (FPR) activation. We evaluated cardiovascular parameters in Wistar rats treated with FPR or histamine receptor antagonists and inhibitors of the nitric oxide pathway before and after F-MIT infusion. F-MIT, but not nonformylated peptides or mitochondrial DNA, induced severe hypotension via FPR activation and nitric oxide and histamine release. Moreover, F-MIT infusion induced hyperthermia, blood clotting, and increased vascular permeability. To evaluate the role of leukocytes in F-MIT-induced hypotension, neutrophil, basophil, or mast cells were depleted. Depletion of basophils, but not neutrophils or mast cells, abolished F-MIT-induced hypotension. Rats that underwent hemorrhagic shock increased plasma levels of mitochondrial formylated proteins associated with lung damage and antagonism of FPR ameliorated hemorrhagic shock-induced lung injury. Finally, F-MIT induced vasodilatation in isolated resistance arteries via FPR activation; however, F-MIT impaired endothelium-dependent relaxation in the presence of blood. These data suggest that F-MIT may be the link among trauma, SIRS, and cardiovascular collapse. Copyright © 2015 the American Physiological Society.

  3. Viral O-GalNAc peptide epitopes

    DEFF Research Database (Denmark)

    Olofsson, Sigvard; Blixt, Klas Ola; Bergström, Tomas

    2016-01-01

    on a novel three-step procedure that identifies any reactive viral O-glycosyl peptide epitope with respect to (i) relevant peptide sequence, (ii) the reactive glycoform out of several possible glycopeptide isomers of that peptide sequence, and (iii) possibly tolerated carbohydrate or peptide structural...

  4. Neoglycolipidation for modulating peptide properties

    DEFF Research Database (Denmark)

    van Witteloostuijn, Søren Blok

    The alarming increase in the prevalence of obesity and associated comorbidities such as type 2 diabetes emphasizes the urgent need for new drugs with both anorectic and antidiabetic eects. Several peptide hormones secreted from the gastrointestinal tract play an important role in the physiological...... regulation of appetite, food intake, and glucose homeostasis, and many of these peptides display a signicant potential for treatment of obesity and/or type 2 diabetes. This Ph.D. thesis describes three novel approaches for utilizing gut peptides as the starting point for developing obesity and diabetes drugs...... of food intake, which was enhanced compared to native NMU. Project II explored the design, synthesis, and characterization of neoglycolipidated analogs of glucagon-like peptide 1 (GLP-1). Neoglycolipidation reduced lipophilicity and maintained or even improved in vitro potency towards the GLP-1 receptor...

  5. Neoglycolipidation for modulating peptide properties

    DEFF Research Database (Denmark)

    van Witteloostuijn, Søren Blok

    regulation of appetite, food intake, and glucose homeostasis, and many of these peptides display a signicant potential for treatment of obesity and/or type 2 diabetes. This Ph.D. thesis describes three novel approaches for utilizing gut peptides as the starting point for developing obesity and diabetes drugs...... of this thesis contribute to emphasize the tremendous therapeutic potential of gut peptides for treatment of obesity and diabetes.......The alarming increase in the prevalence of obesity and associated comorbidities such as type 2 diabetes emphasizes the urgent need for new drugs with both anorectic and antidiabetic eects. Several peptide hormones secreted from the gastrointestinal tract play an important role in the physiological...

  6. Therapeutical Potential of Venom Peptides

    Directory of Open Access Journals (Sweden)

    İlker Kelle

    2006-01-01

    Full Text Available The term of pharmazooticals is known as a few amount of drugs derived from natural sources such as plants, venomous species of snakes, spiders, scorpions, frogs, lizards and cone snails. Peptide components of venoms are directed against wide variety of pharmacological targets such as ion channels and receptors. At the beginning, a number of these peptides have been used in experimental studies for defining the physiological, biochemical and immunological activities of organisms like mammalians. In recent studies, it has been shown that venom peptides can be valuable in treatment of acute and chronic pain, autoimmune and cardiovascular diseases, neurological disorders and chronic inflammatory and tumoral processes. Therefore particularly in clinical approaches, these peptide molecules or their synthetic analogues are considered as alternative agents that can be used instead of classical drugs for many clinical disorders due to their potent activity besides very few side effects.

  7. Antimicrobial peptides from Capsicum sp.

    African Journals Online (AJOL)

    ajl yemi

    2011-12-30

    Dec 30, 2011 ... pathogens, it is a challenge to sustain food production. *Corresponding ... Genetically modified plants (GMPs) resistance to plant pathogens are an .... tically developed peptides have been tested in topic treatments during ...

  8. Nicotine mediates expression of genes related to antioxidant capacity and oxidative stress response in HIV-1 transgenic rat brain.

    Science.gov (United States)

    Song, Guohua; Nesil, Tanseli; Cao, Junran; Yang, Zhongli; Chang, Sulie L; Li, Ming D

    2016-02-01

    Oxidative stress plays an important role in the progression of HIV-1 infection. Nicotine can either protect neurons from neurodegeneration or induce oxidative stress, depending on its dose and degree of oxidative stress impairment. However, the relationship between nicotine and oxidative stress in the HIV-1-infected individuals remains largely unknown. The purpose of this study was to determine the effect of nicotine on expression of genes related to the glutathione (GSH)-centered antioxidant system and oxidative stress in the nucleus accumbens (NAc) and ventral tegmental area (VTA) of HIV-1 transgenic (HIV-1Tg) and F344 control rats. Adult HIV-1Tg and F344 rats received nicotine (0.4 mg/kg, base, s.c.) or saline injections once per day for 27 days. At the end of treatment, various brain regions including the NAc and VTA were collected from each rat. Following total RNA extraction and complementary DNA (cDNA) synthesis of each sample, quantitative reverse transcription PCR (RT-PCR) analysis was performed for 43 oxidative-stress-related genes. Compared with F344 control rats, HIV-1Tg rats showed a significant downregulation of genes involved in ATPase and cyctochrome oxidase at the messenger RNA (mRNA) level in both regions. Further, we found a significant downregulation of Gstm5 in the NAc and upregulation of Cox1, Cox3, and Gsta6 in the VTA of HIV-1Tg rats. HIV-1Tg rats showed brain-region-specific responses to chronic nicotine treatment. This response resulted in a change in the expression of genes involved in antioxidant mechanisms including the downregulation of genes such as Atp5h, Calml1, Gpx7, Gstm5, Gsr, and Gsta6 and upregulation of Sod1 in the NAc, as well as downregulation of genes like Cox5a, Gpx4, Gpx6, Gpx7, Gstm5, and Sod1 in the VTA of HIV-1Tg rats. Together, we conclude that chronic nicotine treatment has a dual effect on the antioxidant defense system and oxidative-stress-induced apoptosis signaling in HIV-1Tg rats. These findings suggest that

  9. Peptides and proteins

    Energy Technology Data Exchange (ETDEWEB)

    Bachovchin, W.W.; Unkefer, C.J.

    1994-12-01

    Advances in magnetic resonance and vibrational spectroscopy make it possible to derive detailed structural information about biomolecular structures in solution. These techniques are critically dependent on the availability of labeled compounds. For example, NMR techniques used today to derive peptide and protein structures require uniformity {sup 13}C-and {sup 15}N-labeled samples that are derived biosynthetically from (U-6-{sup 13}C) glucose. These experiments are possible now because, during the 1970s, the National Stable Isotope Resource developed algal methods for producing (U-6-{sup 13}C) glucose. If NMR techniques are to be used to study larger proteins, we will need sophisticated labelling patterns in amino acids that employ a combination of {sup 2}H, {sup 13}C, and {sup 15}N labeling. The availability of these specifically labeled amino acids requires a renewed investment in new methods for chemical synthesis of labeled amino acids. The development of new magnetic resonance or vibrational techniques to elucidate biomolecular structure will be seriously impeded if we do not see rapid progress in labeling technology. Investment in labeling chemistry is as important as investment in the development of advanced spectroscopic tools.

  10. Antimicrobial peptides in crustaceans

    Directory of Open Access Journals (Sweden)

    RD Rosa

    2010-11-01

    Full Text Available Crustaceans are a large and diverse invertebrate animal group that mounts a complex and efficient innate immune response against a variety of microorganisms. The crustacean immune system is primarily related to cellular responses and the production and release of important immune effectors into the hemolymph. Antimicrobial proteins and/or peptides (AMPs are key components of innate immunity and are widespread in nature, from bacteria to vertebrate animals. In crustaceans, 15 distinct AMP families are currently recognized, although the great majority (14 families comes from members of the order Decapoda. Crustacean AMPs are generally cationic, gene-encoded molecules that are mainly produced by circulating immune-competent cells (hemocytes or are derived from unrelated proteins primarily involved in other biological functions. In this review, we tentatively classified the crustacean AMPs into four main groups based on their amino acid composition, structural features and multi-functionality. We also attempted to summarize the current knowledge on their implication both in an efficient response to microbial infections and in crustacean survival.

  11. Antimicrobial peptides in annelids

    Directory of Open Access Journals (Sweden)

    A Tasiemski

    2008-06-01

    Full Text Available Gene encoded antimicrobial peptides (AMPs are widely distributed among living organisms including plants, invertebrates and vertebrates. They constitute important effectors of the innate immune response by exerting multiple roles as mediators of inflammation with impact on epithelial and inflammatory cells influencing diverse processes such as cytokine release, cell proliferation, angiogenesis, wound healing, chemotaxis and immune induction. In invertebrates, most of the data describe the characterization and/or the function of AMPs in the numerically and economically most representative group which are arthropods. Annelids are among the first coelomates and are therefore of special phylogenetic interest. Compared to other invertebrate groups, data on annelid’s immunity reveal heavier emphasis on the cellular than on the humoral response suggesting that immune defense of annelids seems to be principally developed as cellular immunity.This paper gives an overview of the variety of AMPs identified in the three classes of annelids, i.e. polychaetes, oligochaetes and achaetes. Their functions, when they have been studied, in the humoral or cellular response of annelids are also mentioned.

  12. Production of nitric oxide using a microwave plasma torch and its application to fungal cell differentiation

    Science.gov (United States)

    Na, Young Ho; Kumar, Naresh; Kang, Min-Ho; Cho, Guang Sup; Choi, Eun Ha; Park, Gyungsoon; Uhm, Han Sup

    2015-03-01

    The generation of nitric oxide by a microwave plasma torch is proposed for its application to cell differentiation. A microwave plasma torch was developed based on basic kinetic theory. The analytical theory indicates that nitric oxide density is nearly proportional to oxygen molecular density and that the high-temperature flame is an effective means of generating nitric oxide. Experimental data pertaining to nitric oxide production are presented in terms of the oxygen input in units of cubic centimeters per minute. The apparent length of the torch flame increases as the oxygen input increases. The various levels of nitric oxide are observed depending on the flow rate of nitrogen gas, the mole fraction of oxygen gas, and the microwave power. In order to evaluate the potential of nitric oxide as an activator of cell differentiation, we applied nitric oxide generated from the microwave plasma torch to a model microbial cell (Neurospora crassa: non-pathogenic fungus). Germination and hyphal differentiation of fungal cells were not dramatically changed but there was a significant increase in spore formation after treatment with nitric oxide. In addition, the expression level of a sporulation related gene acon-3 was significantly elevated after 24 h upon nitric oxide treatment. Increase in the level of nitric oxide, nitrite and nitrate in water after nitric oxide treatment seems to be responsible for activation of fungal sporulation. Our results suggest that nitric oxide generated by plasma can be used as a possible activator of cell differentiation and development.

  13. Interleukin 1 beta induces diabetes and fever in normal rats by nitric oxide via induction of different nitric oxide synthases

    DEFF Research Database (Denmark)

    Reimers, J I; Bjerre, U; Mandrup-Poulsen, T

    1994-01-01

    Substantial in vitro evidence suggests that nitric oxide may be a major mediator of interleukin 1 (IL-1) induced pancreatic beta-cell inhibition and destruction in the initial events leading to insulin-dependent diabetes mellitus. Using NG-nitro-L-arginine methyl ester, an inhibitor of both......, glucagon, corticosterone and leukocyte- and differential-counts in normal rats injected once daily for 5 days with interleukin 1 beta (IL-1 beta) (0.8 microgram/rat = 4.0 micrograms/kg). Inhibition of both the constitutive and the inducible forms of nitric oxide synthase prevented IL-1 beta-induced fever...

  14. Adrenomedullin A Novel Peptide Requires Coordination Of Genetic Physiologic And Environmental Factors

    Directory of Open Access Journals (Sweden)

    K. R. Padma

    2015-08-01

    Full Text Available A healthy pregnancy requires strict coordination of genetic physiologic and environmental factors. The relatively common incidence of infertility and pregnancy complications has resulted in increased interest in understanding the mechanisms that underlie normal versus abnormal pregnancy. The peptide hormone adrenomedullin has recently been the focus of some exciting breakthroughs in the pregnancy field. Adrenomedullin ADM is a 52-amino acid peptide with structural homology to calcitonin gene-related peptide CGRP initially isolated from human pheochromocytoma. ADM is synthesized by many mammalian tissues including the adrenal medulla endothelial and vascular smooth muscle cells myocardium and central nervous system. ADM binds to plasma membrane receptors composed of calcitonin receptor-like receptor CRLR a member of serpentine receptor superfamily and receptor activity modifying protein RAMP type 2 or 3. ADM has also some affinity for CGRP receptor composed of CRLR and RAMP1. Supported by mechanistic studies in genetic animal models there continues to be a growing body of evidence demonstrating the importance of adrenomedullin protein levels in a variety of human pregnancy complications. With measurement of foetal resorption sites we can examine the importance of adrenomedullin a peptide hormone in pregnancy which alters due to genetic physiologic and environmental factors. A growing body of evidence illustrates AM as a pivotal component in normal physiology and disease with marked beneficial effects in the host defense mechanism.

  15. 侧脑室注射肾上腺髓质素增加大鼠心血管相关核团中c-fos的表达并激活脑内一氧化氮神经元%Intracerebroventricular administration of adrenomedullin increases the expression of c-fos and activates nitric oxide-producing neurons in rat cardiovascular related brain nuclei

    Institute of Scientific and Technical Information of China (English)

    季淑梅; 王泽民; 李学平; 何瑞荣

    2004-01-01

    本研究利用Fos蛋白和一氧化氮合酶(nNOS)双重免疫组化方法,观察侧脑室注射肾上腺髓质素(adrenomedullin,ADM)对大鼠心血管相关核团中c-fos表达及一氧化氮神经元的影响,以探讨ADM在中枢的作用部位并研究其在中枢的作用是否有NO神经元参与.侧脑室注射ADM(1 nmol/kg,3 nmol/kg)诱发脑干的孤束核、最后区、蓝斑核、臂旁核和外侧巨细胞旁核,下丘脑的室旁核、视上核和腹内侧核以及前脑的中央杏仁核和外侧缰核等多个部位的心血管中枢出现大量Fos样免疫反应神经元.侧脑室注射ADM(3 nmol/kg)引起脑干的孤束核、外侧巨细胞旁核,下丘脑的室旁核、视上核内的Fos-nNOS双标神经元增加;ADM(1 nmol/kg)亦可引起室旁核、视上核内的Fos-nNOS双标神经元增加,而对孤束核、外侧巨细胞旁核内的Fos-nNOS双标神经元无影响.降钙素基因相关肽(calcitonin gene-related peptide,CGRP)受体拮抗剂CGRP8-37(30 nmol/kg)可明显减弱此效应.以上结果表明,ADM可兴奋脑内多个心血管相关核团的神经元并激活室旁核、视上核、孤束核及外侧巨细胞旁核内的一氧化氮神经元,此效应可能部分由CGRP受体介导.%To define the action sites of adrenomedullin (ADM) in the rat brain, and to examine whether neuronal NO may participate in the actions of ADM, the present study was undertaken to examine the effects of i.c.v. administration of ADM on the induction of Fos protein and on nitric oxide-producing neurons in rat brain nuclei involved in cardiovascular regulation, using double immunohistochemical method for Fos and neuronal nitric oxide synthase (nNOS). Following i.c.v. administration of ADM (1 mol/kg, 3 mol/kg), Fos-like immunoreactivity neurons were markedly increased in several brain areas of the rat, including the nucleus of the solitary tract (NTS), the area postrema, the locus coeruleus, the parabrachial nucleus and the nucleus paragigantocelluaris

  16. Molecular Cloning, Bioinformatic Analysis, and Expression of Bombyx mori Lebocin 5 Gene Related to Beauveria bassiana Infection.

    Science.gov (United States)

    Lü, Dingding; Hou, Chengxiang; Qin, Guangxing; Gao, Kun; Chen, Tian; Guo, Xijie

    2017-01-01

    A full-length cDNA of lebocin 5 (BmLeb5) was first cloned from silkworm, Bombyx mori, by rapid amplification of cDNA ends. The BmLeb5 gene is 808 bp in length and the open reading frame encodes a 179-amino acid hydroxyproline-rich peptide. Bioinformatic analysis results showed that BmLeb5 owns an O-glycosylation site and four RXXR motifs as other lebocins. Sequence similarity and phylogenic analysis results indicated that lebocins form a multiple gene family in silkworm as cecropins. Quantitative real-time PCR analysis revealed that BmLeb5 was highest expressed in the fat body. In the silkworm larvae infected by Beauveria bassiana, the expression level of BmLeb5 was upregulated in the fat body and hemolymph which are the most important immune tissues in silkworm. The recombinant protein of BmLeb5 was for the first time successfully expressed with prokaryotic expression system and purified. There are no reports so far that the expression of lebocins could be induced by entomopathogenic fungus. Our study suggested that BmLeb5 might play an important role in the immune response of silkworm to defend B. bassiana infection. The results also provided helpful information for further studying the lebocin family functioned in antifungal immune response in the silkworm.

  17. Molecular Cloning, Bioinformatic Analysis, and Expression of Bombyx mori Lebocin 5 Gene Related to Beauveria bassiana Infection

    Science.gov (United States)

    Lü, Dingding; Hou, Chengxiang; Qin, Guangxing; Gao, Kun; Chen, Tian

    2017-01-01

    A full-length cDNA of lebocin 5 (BmLeb5) was first cloned from silkworm, Bombyx mori, by rapid amplification of cDNA ends. The BmLeb5 gene is 808 bp in length and the open reading frame encodes a 179-amino acid hydroxyproline-rich peptide. Bioinformatic analysis results showed that BmLeb5 owns an O-glycosylation site and four RXXR motifs as other lebocins. Sequence similarity and phylogenic analysis results indicated that lebocins form a multiple gene family in silkworm as cecropins. Quantitative real-time PCR analysis revealed that BmLeb5 was highest expressed in the fat body. In the silkworm larvae infected by Beauveria bassiana, the expression level of BmLeb5 was upregulated in the fat body and hemolymph which are the most important immune tissues in silkworm. The recombinant protein of BmLeb5 was for the first time successfully expressed with prokaryotic expression system and purified. There are no reports so far that the expression of lebocins could be induced by entomopathogenic fungus. Our study suggested that BmLeb5 might play an important role in the immune response of silkworm to defend B. bassiana infection. The results also provided helpful information for further studying the lebocin family functioned in antifungal immune response in the silkworm. PMID:28194425

  18. The role of non-synonymous NPY gene polymorphism in the nitric oxide production in HUVECs.

    Science.gov (United States)

    Kaipio, Katja; Vahlberg, Tero; Suominen, Marianne; Pesonen, Ullamari

    2009-04-17

    A Leu7Pro change in the signal peptide of preproNPY is a functional substitution, which changes the processing of NPY in cells and associates with several cardiovascular and metabolic conditions in humans. The current study investigates the effect of the P7 allele in endothelial cells, where decreased nitric oxide (NO) production is a promoting factor to endothelial dysfunction. The function of NO system was assessed in the human umbilical vein endothelial cells (HUVECs) with [p.L7]+[p.L7] or [p.L7]+[p.P7] genotype. NPY seems to have a significant influence on NO system in HUVECs, and the responses are time and genotype dependent. HUVECs with [p.L7]+[p.P7] genotype seem to have higher basal production of NO, but after a long term treatment with NPY these cells express less eNOS mRNA and overall eNOS protein levels are lower. These significant differences in the NO bioavailability may explain the association of the L7P polymorphism with several cardiovascular complications.

  19. Sucrose-induced analgesia in mice: Role of nitric oxide and opioid receptor-mediated system

    Directory of Open Access Journals (Sweden)

    Abtin Shahlaee

    2013-01-01

    Full Text Available Background: The mechanism of action of sweet substance-induced analgesia is thought to involve activation of the endogenous opioid system. The nitric oxide (NO pathway has a pivotal role in pain modulation of analgesic compounds such as opioids. Objectives: We investigated the role of NO and the opioid receptor-mediated system in the analgesic effect of sucrose ingestion in mice. Materials and Methods: We evaluated the effect of intraperitoneal administration of 10 mg/kg of NO synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME and 20 mg/kg of opioid receptor antagonist, naltrexone on the tail flick response in sucrose ingesting mice. Results: Sucrose ingestion for 12 days induced a statistically significant increase in the latency of tail flick response which was unmodified by L-NAME, but partially inhibited by naltrexone administration. Conclusions: Sucrose-induced nociception may be explained by facilitating the release of endogenous opioid peptides. Contrary to some previously studied pain models, the NO/cyclic guanosine monophosphate (cGMP pathway had no role in thermal hyperalgesia in our study. We recommend further studies on the involvement of NO in other animals and pain models.

  20. Effects of Nephritis No. 3 Recipe on Nitric Oxide, Nitric Oxide Synthase Secreted by Cultured Mesangial Cells in Rats and the Gene Expression of Inducible Nitric Oxide Synthase

    Institute of Scientific and Technical Information of China (English)

    陈志强; 黄怀鹏; 黄文政; 朱小棣; 林清棋

    2003-01-01

    Objective: To explore the effect of the Nephritis No. 3 (N-3) recipe on nitric oxide (NO),nitric oxide synthase (NOS) secreted by cultured mesangial cells (MC) and its gene expression of the inducible nitric oxide synthase (iNOS). Methods: The drug (nephritis No. 3)-containing serum was prepared with serum pharmacological technique, and then was applied to react on mesangial cells cultured in fetal calf serum (FCS) and cells cultured in FCS plus lipopolysaccharide. To observe the secretion of NO and NOS and the gene expression of iNOS by means of RT-PCR. Results: Under the two kinds of culture conditions, the content of NO and NOS in the groups with drug-containing serum were higher than those without drug-containing serum (P<0.05, P<0.01), and the expression of iNOS mRNA was up-regulated too. Conclusion: The N-3 could significantly promote the secretion of NO and NOS and the mRNA expression of iNOS in rats.

  1. Nitric oxide-induced signalling in rat lacrimal acinar cells

    DEFF Research Database (Denmark)

    Looms, Dagnia Karen; Tritsaris, K.; Dissing, S.

    2002-01-01

    The aim of the present study was to investigate the physiological role of nitric oxide (NO) in mediating secretory processes in rat lacrimal acinar cells. In addition, we wanted to determine whether the acinar cells possess endogenous nitric oxide synthase (NOS) activity by measuring NO productio...... not by itself causing fast transient increases in [Ca2+]i. In addition, we suggest that endogenously produced NO activated by ß-adrenergic receptor stimulation, plays an important role in signalling to the surrounding tissue.......The aim of the present study was to investigate the physiological role of nitric oxide (NO) in mediating secretory processes in rat lacrimal acinar cells. In addition, we wanted to determine whether the acinar cells possess endogenous nitric oxide synthase (NOS) activity by measuring NO production......-adrenergic stimulation and not by a rise in [Ca2+]i alone.   We show that in rat lacrimal acinar cells, NO and cGMP induce Ca2+ release from intracellular stores via G kinase activation. However, the changes in [Ca2+]i are relatively small, suggesting that this pathway plays a modulatory role in Ca2+ signalling, thus...

  2. Nitric oxide affects sarcoplasmic calcium release in skeletal myotubes.

    NARCIS (Netherlands)

    Heunks, L.M.A.; Machiels, H.A.; Dekhuijzen, P.N.R.; Prakash, Y.S.; Sieck, G.C.

    2001-01-01

    In the present study, we used real-time confocal microscopy to examine the effects of two nitric oxide (NO) donors on acetylcholine (ACh; 10 microM)- and caffeine (10 mM)-induced intracellular calcium concentration ([Ca2+]i) responses in C2C12 mouse skeletal myotubes. We hypothesized that NO reduces

  3. NITRIC OXIDE INTERFERES WITH HYPOXIA SIGNALING DURING COLONIC INFLAMMATION

    Directory of Open Access Journals (Sweden)

    Cintia Rabelo e Paiva CARIA

    2014-12-01

    Full Text Available Context Intestinal inflammation can induce a local reduction in oxygen levels that triggers an adaptive response centered on the expression of hypoxia-inducible factors (HIFs. Nitric oxide, a well-described inflammatory mediator, may interfere with hypoxia signaling. Objectives We aimed to evaluate the role of nitric oxide in hypoxia signaling during colonic inflammation. Methods Colitis was induced by single (acute or repeated (reactivated colitis trinitrobenzenosulfonic acid administration in rats. In addition, one group of rats with reactivated colitis was also treated with Nw-Nitro-L-arginine methyl ester hydrochloride to block nitric oxide synthase. Colitis was assessed by macroscopic score and myeloperoxidase activity in the colon samples. Hypoxia was determined using the oxygen-dependent probe, pimonidazole. The expression of HIF-1α and HIF-induced factors (vascular endothelial growth factor - VEGF and apelin was assessed using Western blotting. Results The single or repeated administration of trinitrobenzenosulfonic acid to rats induced colitis which was characterized by a high macroscopic score and myeloperoxidase activity. Hypoxia was observed with both protocols. During acute colitis, HIF-1α expression was not increased, but VEGF and apelin were increased. HIF-1α expression was inhibited during reactivated colitis, and VEGF and apelin were not increased. Nw-Nitro-L-arginine methyl ester hydrochloride blockade during reactivated colitis restored HIF-1α, VEGF and apelin expression. Conclusions Nitric oxide could interfere with hypoxia signaling during reactivated colitis inflammation modifying the expression of proteins regulated by HIF-1α.

  4. Nitric oxide and carbon monoxide diffusing capacity of the lung

    NARCIS (Netherlands)

    Lee, I. van der

    2006-01-01

    The single breath diffusion capacity of the lung for carbon monoxide (DLCO) is measure for gas uptake by the lung, and consists of a membrane and a vascular component. Nitric oxide (NO) binds 400 times faster to hemoglobin than carbon monoxide, thus the uptake of NO by the blood is very large.

  5. The levels of nitric oxide in megaloblastic anemia

    Directory of Open Access Journals (Sweden)

    Emin Kaya

    2009-12-01

    Full Text Available Objective: The purpose of this study was to investigate the relationship between nitric oxide degradation products (nitrate and nitrite levels and megaloblastic anemia which is treated with cyalocobalamin. Materials and Methods: A total of 30 patients with megaloblastic anemia (16 Male, 14 Female were included in the study. Cyanocobalamin was administered (1.000 µg/day intramuscularly until the reticulocyte crisis occurred to the normal range. The control group consisted of 30 healthy subjects (15 Male, 15 Female. Nitric oxide levels were measured before treatment and compared with the values obtained during peak reticulocyte count. Results: Plasma direct nitrite, total nitrite and nitrate levels were 24,86±3,87, 60.56±7,01 and 36,02±5,24 in before treatment versus 15,48±3,05, 38,92±6,44 and 22,77±6,04 μmol/dl in after treatment, respectively. Plasma direct nitrite, total nitrite and nitrate levels were significantly lower in after treatment compared with the before treatment (p<0.001. Conclusion: Nitric oxide levels are seen to increase in megaloblastic anemia. This study suggested that abnormalities in the nitric oxide levels in megaloblastic anemia are restored by vitamin B12 replacement therapy.

  6. Simulated dry deposition of nitric acid near forest edges

    NARCIS (Netherlands)

    DeJong, JJM; Klaassen, W; Jong, J.J.M. de

    1997-01-01

    Dry deposition is simulated to understand and generalize observations of enhanced deposition of air pollution near forest edges. Nitric acid is taken as an example as its deposition velocity is often assumed to be determined by turbulent transport only. The simulations are based on the micro-meteoro

  7. Arginine, citrulline and nitric oxide metabolism in sepsis

    Science.gov (United States)

    Arginine has vasodilatory effects, via its conversion by nitric oxide (NO) synthase into NO, and immunomodulatory actions that play important roles in sepsis. Protein breakdown affects arginine availability, and the release of asymmetric dimethylarginine, an inhibitor of NO synthase, may therefore a...

  8. Water vapour and carbon dioxide decrease nitric oxide readings

    NARCIS (Netherlands)

    vanderMark, TW; Kort, E; Meijer, RJ; Postma, DS; Koeter, GH

    Measurement of nitric oxide levels in exhaled ah-is commonly performed using a chemiluminescence detector. However, water vapour and carbon dioxide affect the chemiluminescence process, The influence of these gases at the concentrations present in exhaled air has not vet been studied. For this in

  9. Deficiency of nitric oxide in polycation-induced airway hyperreactivity

    NARCIS (Netherlands)

    Meurs, Herman; Schuurman, F.E; Duyvendak, M; Zaagsma, Hans

    1999-01-01

    Using a perfused guinea-pig tracheal tube preparation, we investigated the role of endogenous nitric oxide (NO) in polycation-induced airway hyperreactivity (AHR) to methacholine. Intraluminal (IL) administration of the NO synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME; 100 mu M) c

  10. Evaluation of serum nitric oxide before and after local ...

    African Journals Online (AJOL)

    Hoda Aly Abd-El Moety

    2012-10-06

    Oct 6, 2012 ... Chronic hepatitis C virus is one of the main risk factors for the development of. Hepatocellular carcinoma ... either sub-Saharan Africa or in eastern Asia.1,2 Risk factors that lead to the ..... Yuen Man-Fung, Lai Ching-Lung. Serological .... Nitric oxide of human colorectal adenocarcinoma cell lines promotes ...

  11. Apple fruit responses following exposure to nitric oxide

    Science.gov (United States)

    Exogenous nitric oxide (.NO) applied as gas or generated from .NO releasing compounds has physiological activity in cut apple fruit tissues. Studies were conducted to characterize .NO production by whole fruit as well as to assess responses of whole fruit to exogenous .NO. .NO and ethylene product...

  12. Cross sections for electron collisions with nitric oxide

    Science.gov (United States)

    Itikawa, Yukikazu

    2016-09-01

    Cross section data are reviewed for electron collisions with nitric oxide. Collision processes considered are total scattering, elastic scattering, momentum transfer, excitations of rotational, vibrational, and electronic states, ionization, and dissociative electron attachment. After a survey of the literature (up to the end of 2015), recommended values of the cross section are determined, as far as possible.

  13. Generation of nitric oxide from nitrite by carbonic anhydrase:

    DEFF Research Database (Denmark)

    Aamand, Rasmus; Dalsgaard, Thomas; Jensen, Frank Bo;

    2009-01-01

    bicarbonate and nitrite, we hypothesized that CA uses nitrite as a substrate to produce the potent vasodilator nitric oxide (NO) to increase local blood flow to metabolically active tissues. Here we show that CA readily reacts with nitrite to generate NO, particularly at low pH, and that the NO produced...

  14. On EPR detection of nitric oxide in vivo

    NARCIS (Netherlands)

    van Faassen, E.E.H.

    2008-01-01

    Nitric oxide (NO ) is a peculiar radical: Ground state is not paramagnetic (g = 0 since orbital and spin magnetic moments cancel); low reactivity with other molecules except superoxide (O2 ); thermodynamically unstable; dimerizes to N2O2; difficult to detect in-vivo.

  15. Nitric oxide as a potent fumigant for postharvest pest control

    Science.gov (United States)

    There is a great demand for safe and effective alternative fumigants to replace methyl bromide and other toxic fumigants for pest control. Nitric oxide, a common signal molecule in biological systems, was found to be effective and safe to control insects under ultralow oxygen conditions. Fumigatio...

  16. Nitric oxide and carbon monoxide diffusing capacity of the lung

    NARCIS (Netherlands)

    Lee, I. van der

    2006-01-01

    The single breath diffusion capacity of the lung for carbon monoxide (DLCO) is measure for gas uptake by the lung, and consists of a membrane and a vascular component. Nitric oxide (NO) binds 400 times faster to hemoglobin than carbon monoxide, thus the uptake of NO by the blood is very large. There

  17. Inhibition of influenza virus replication by nitric oxide

    NARCIS (Netherlands)

    G.F. Rimmelzwaan (Guus); M.M.J.W. Baars (Marianne); P. de Lijster; R.A.M. Fouchier (Ron); A.D.M.E. Osterhaus (Albert)

    1999-01-01

    textabstractNitric oxide (NO) has been shown to contribute to the pathogenesis of influenza virus-induced pneumonia in mouse models. Here we show that replication of influenza A and B viruses in Mabin Darby canine kidney cells is severely impaired by the NO donor,

  18. Egg-derived tri-peptide IRW exerts antihypertensive effects in spontaneously hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Kaustav Majumder

    Full Text Available BACKGROUND: There is a growing interest in using functional food components as therapy for cardiovascular diseases such as hypertension. We have previously characterized a tri-peptide IRW (Ile-Arg-Trp from egg white protein ovotransferrin; this peptide showed anti-inflammatory, anti-oxidant and angiotensin converting enzyme (ACE inhibitor properties in vitro. Given the pathogenic roles played by angiotensin, oxidative stress and inflammation in the spontaneously hypertensive rat (SHR, we tested the therapeutic potential of IRW in this well-established model of hypertension. METHODS AND RESULTS: 16-17 week old male SHRs were orally administered IRW at either a low dose (3 mg/Kg BW or a high dose (15 mg/Kg BW daily for 18 days. Blood pressure (BP and heart rate were measured by telemetry. Animals were sacrificed at the end of the treatment for vascular function studies and measuring markers of inflammation. IRW treatment attenuated mean BP by ~10 mmHg and ~40 mmHg at the low- and high-dose groups respectively compared to untreated SHRs. Heart rate was not affected. Reduction in BP was accompanied by the restoration of diurnal variations in BP, preservation of nitric oxide dependent vasorelaxation, as well as reduction of plasma angiotensin II, other inflammatory markers and tissue fibrosis. CONCLUSION: Our results demonstrate anti-hypertensive effects of IRW in vivo likely mediated through ACE inhibition, endothelial nitric oxide synthase and anti-inflammatory properties.

  19. Effects of glucocorticoid dexamethasone on serum nitric oxide synthase activity and nitric oxide levels in a rat model of lung disease-induced brain injury

    Institute of Scientific and Technical Information of China (English)

    Huajun Li; Ligang Jiang; Meng Xia; Haiping Li; Fanhua Meng; Wei Li; Lifeng Liu; Zhaohui Wang

    2011-01-01

    In this study, we investigated the effects of dexamethasone, pertussis toxin (a Gi protein inhibitor), and actinomycin (a transcription inhibitor) on serum nitric oxide synthase activity and nitric oxide content in a rat model of lung disease-induced brain injury. High-dose dexamethasone (13 mg/kg) and dexamethasone + actinomycin reduced lung water content, increased serum nitric oxide synthase activity and nitric oxide content, diminished inflammatory cell infiltration in pulmonary alveolar interstitium, attenuated meningeal vascular hyperemia, reduced glial cell infiltration, and decreased cerebral edema. These results demonstrate that high-dose glucocorticoid treatment can reduce the severity of lung disease-induced brain injury by increasing nitric oxide synthase activity and nitric oxide levels.

  20. Peptides and Anti-peptide Antibodies for Small and Medium Scale Peptide and Anti-peptide Affinity Microarrays: Antigenic Peptide Selection, Immobilization, and Processing.

    Science.gov (United States)

    Zhang, Fan; Briones, Andrea; Soloviev, Mikhail

    2016-01-01

    This chapter describes the principles of selection of antigenic peptides for the development of anti-peptide antibodies for use in microarray-based multiplex affinity assays and also with mass-spectrometry detection. The methods described here are mostly applicable to small to medium scale arrays. Although the same principles of peptide selection would be suitable for larger scale arrays (with 100+ features) the actual informatics software and printing methods may well be different. Because of the sheer number of proteins/peptides to be processed and analyzed dedicated software capable of processing all the proteins and an enterprise level array robotics may be necessary for larger scale efforts. This report aims to provide practical advice to those who develop or use arrays with up to ~100 different peptide or protein features.