International Nuclear Information System (INIS)

In vivo effects of toxaphene on calcium pump activity in rat brain synaptosomes was studied. Male Sprague-Dawley rats were dosed with toxaphene at 0,25,50, and 100 mg/kg/day for 3 days and sacrificed 24 h after last dose. Ca"2"+-ATPase activity and "4"5Ca uptake were determined in brain P_2 fraction. Toxaphene inhibited both Ca"2"+-ATPase activity and "4"5Ca"2"+ uptake and the inhibition was dose dependent. Both substrate and Ca"2"+ activation kinetics of Ca"2"+-ATPase indicated non-competitive type of inhibition as evidenced by decreased catalytic velocity but not enzyme-substrate affinity. The inhibited Ca"2"+-ATPase activity and Ca"2"+ uptake were restored to normal level by exogenously added ...

DEFF Research Database (Denmark)

Efflux of dopamine through the dopamine transporter (DAT) is critical for the psychostimulatory properties of amphetamines, but the underlying mechanism is unclear. Here we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a key role in this efflux. CaMKIIalpha bound to the distal C terminus of DAT and colocalized with DAT in dopaminergic neurons. CaMKIIalpha stimulated dopamine efflux via DAT in response to amphetamine in heterologous cells and in dopaminergic neurons. CaMKIIalpha phosphorylated serines in the distal N terminus of DAT in vitro, and mutation of these serines eliminated the stimulatory effects of CaMKIIalpha. A mutation of the DAT C terminus impairing CaMKIIalpha binding also impaired amphetamine-induced dopamine efflux. An in vivo role for CaMKII was supported by chronoamperometry measurements showing reduced amphetamine-induced dopamine efflux in response to the CaMKII inhibitor KN93. ...

Science.gov (United States)

beta-Bungarotoxin (beta-Bgt), a presynaptic phospholipase A(2) (PLA(2)) neurotoxin isolated from the venom of Bungarus multicinctus, consists of A chain and B chain. The goal of the present study is to explore the functional contribution of the two subunits to the toxicity of beta-Bgt. beta-Bgt was found to induce apoptotic death of SK-N-SH cells via elevating intracellular Ca(2+) and intracellular ROS production. Moreover, an activation of p38 MAPK was associated with the cytotoxicity of beta-Bgt. SB202190 (p38 MAPK inhibitor), N-acetylcysteine (antioxidant reagent), 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid (BAPTA) (Ca(2+) chelator) and the inhibitors of Ca(2+) release from intracellular depots (ruthenium red and 2-aminoethoxydiphenyl borate) effectively attenuated the cytotoxicity of beta-Bgt. In sharp contrast to the inability of A chain, B ...

KoreaScience (Korea)

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/sup 125/I-Calmodulin is internalized by isolated rat renal brush border membrane vesicles (BBV) in a time, temperature and calcium dependent manner. Internalization of /sup 125/I-calmodulin into the osmotically sensitive space of BBV was distinguished from binding of the ligand to the outer BBV surface by examining the interaction of ligand and BBV at different medium osmolarities (300-1100 mosm), uptake was inversely proportional to medium osmolarity. Internalized /sup 125/I-calmodulin was intact and Western blots of solubilized BBV with /sup 125/I-calmodulin demonstrated the presence of several calmodulin-binding proteins of 143, 118, 50, 47.5, 46.5 and 35 kilodaltons which could represent potential intravesicular binding sites for the ligand. Heparin and the related glycosaminoglycan heparin sulfate both showed a dose-dependent inhibition (0.5-50 ..mu..g/ml) of /sup ...

International Nuclear Information System (INIS)

We studied the effect of extracellular Ca"2"+ concentration ([Ca"2"+]_e) on adipocyte differentiation. Preadipocytes exposed to continuous [Ca"2"+]_e higher than 2.5 mmol/l accumulated little or no cytoplasmic lipid compared to controls in 1.8 mmol/l [Ca"2"+]_e. Differentiation was monitored by Oil Red O staining of cytoplasmic lipid and triglyceride assay of accumulated lipid, by RT-PCR analysis of adipogenic markers, and by the activity of glycerol-3-phosphate dehydrogenase (GPDH). Elevated [Ca"2"+]_e inhibited expression of peroxisome proliferator-activated receptor #gamma#, CCAAT/enhancer binding protein #alpha#, and steroid regulatory binding element protein. High [Ca"2"+]_e significantly inhibited differentiation marker expression ...

UK PubMed Central (United Kingdom)

1. Digital imaging and photometry were used in conjunction with the fluorescent Ca2+ indicator, Fura-2, to examine intracellular Ca2+ signals produced by depolarization of single adrenal chromaffin...Full Text Available

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In vivo effects of toxaphene on calcium pump activity in rat brain synaptosomes was studied. Male Sprague-Dawley rats were dosed with toxaphene at 0,25,50, and 100 mg/kg/day for 3 days and sacrificed 24 h after last dose. Ca/sup 2 +/-ATPase activity and /sup 45/Ca uptake were determined in brain P/sub 2/ fraction. Toxaphene inhibited both Ca/sup 2 +/-ATPase activity and /sup 45/Ca/sup 2 +/ uptake and the inhibition was dose dependent. Both substrate and Ca/sup 2 +/ activation kinetics of Ca/sup 2 +/-ATPase indicated non-competitive type of inhibition as evidenced by decreased catalytic velocity but not enzyme-substrate affinity. The inhibited Ca/sup 2 +/-ATPase activity and Ca/sup 2 +/ uptake were restored to normal level by exogenously added calmodulin which increased both velocity and affinity. The inhibition of Ca/sup 2 +/-ATPase activity and Ca/sup 2 +/ uptake and restoration by calmodulin suggests that toxaphene may impair active calcium ...

KoreaScience (Korea)

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Science.gov (United States)

Snake envenomation employs three well integrated strategies: prey immobilization via hypotension, prey immobilization via paralysis, and prey digestion. Purines (adenosine, guanosine and inosine) evidently play a central role in the envenomation strategies of most advanced snakes. Purines constitute the perfect multifunctional toxins, participating simultaneously in all three envenomation strategies. Because they are endogenous regulatory compounds in all vertebrates, it is impossible for any prey organism to develop resistance to them. Purine generation from endogenous precursors in the prey explains the presence of many hitherto unexplained enzyme activities in snake venoms: 5'-nucleotidase, endonucleases (including ribonuclease), phosphodiesterase, ATPase, ADPase, phosphomonoesterase, and NADase. Phospholipases A(2), cytotoxins, myotoxins, and heparinase also participate in purine liberation, in addition to their better known functions. Adenosine contributes to prey immobilization ...

Science.gov (United States)

Electrically triggered action potentials in the giant alga Chara corallina are associated with a transient rise in the concentration of free Ca(2)+ in the cytoplasm (Ca(2)+(cyt)). The present measurements of Ca(2)+(cyt) during membrane excitation show that stimulating pulses of low magnitude (subthreshold pulse) had no perceivable effect on Ca(2)+(cyt). When the strength of a pulse exceeded a narrow threshold (suprathreshold pulse) it evoked the full extent of the Ca(2)+(cyt) elevation. This suggests an all-or-none mechanism for Ca(2)+ mobilization. A transient calcium rise could also be induced by one subthreshold pulse if it was after another subthreshold pulse of the same kind after a suitable interval, i.e., not closer than a few 100 ...

KoreaScience (Korea)

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KoreaScience (Korea)

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International Nuclear Information System (INIS)

We have previously reported that FSH stimulates flux of 45Ca2+ into cultured Sertoli cells from immature rats via voltage-sensitive and voltage-independent calcium channels. In the present study, we show that this effect of FSH does not require cholera toxin (CT)- or pertussis toxin (PT)-sensitive guanine nucleotide binding (G) protein or activation of adenylate cyclase (AC). Significant stimulation of 45Ca2+ influx was observed within 1 min, and maximal response (3.2-fold over basal levels) was achieved within 2 min after exposure to FSH. FSH-stimulated elevations in cellular cAMP paralleled increases in 45Ca2+ uptake, suggesting a possible coupling of AC activation to 45Ca2+ influx. (Bu)2cAMP, however, was not able to enhance 45Ca2+ uptake over basal levels at a final ...

UK PubMed Central (United Kingdom)

A filamentous fungus, Cunninghamella blakesleeana AS 3.153, was used as a microbial model of mammalian metabolism to transform verapamil, a calcium channel antagonist. The metabolites...Full Text Available

British Library Electronic Table of Contents (United Kingdom)

Tumour necrosis factor-alpha (TNF-?) antagonist drugs have been associated with increased risk of tuberculosis (TB). Tuberculin skin test (TST) is the most frequently used tool for identification of latent TB infection. We herein aimed to analyse the effect of TNF-? antagonists on the TST responses in a prospective study. The study group consisted of 182 patients (99 female, 83 male) who received TNF-? antagonists for various rheumatic disorders. All patients were evaluated with TST along with other parameters on the day of referral and on the 12th month visit. For those patients with a response of <5?mm induration at the initial evaluation, the TST was repeated to observe the booster effect. Out of 182 patients, 87 patients (48%) had a negative (0?4?mm) and 95 (52%) had a positive (?5?mm)...

Energy Technology Data Exchange (ETDEWEB)

Electromagnetic fields have been reported to cause a variety of biological effects. It has been hypothesized that many of these phenomena are mediated by a primary effect on the concentration of cytosolic free calcium ((Ca2+)i). We investigated the effects of exposure to electromagnetic fields on (Ca2+)i in HL-60 cells using the Ca2(+)-sensitive fluorescent indicator indo-1. Indo-1-loaded cell samples were exposed to a radiofrequency electromagnetic field, a static magnetic field, and a time-varying magnetic field, which were generated by a magnetic resonance imaging (MRI) unit. We found that a 23-min exposure to all three fields, in combination, induced a significant increase in (Ca2+)i of 31 +/- 8 (SE) nM (P less than 0.01, n = 13) from a basal level of 121 +/- 8 nM. Also, cells exposed to only the time-varying ...

UK PubMed Central (United Kingdom)

1. The effects on micturition of RP 67,580, a selective NK1 receptor antagonist, and SR 48,968, a highly, potent antagonist at NK2 receptor sites, given intrathecally (i.t.) or intra-arterially (i.a.)...Full Text Available

British Library Electronic Table of Contents (United Kingdom)

We performed a randomized trial to compare IVF outcomes in 54 poor responder patients undergoing a microdose leuprolide acetate (LA) protocol or a GnRH antagonist protocol incorporating a luteal phase E2 patch and GnRH antagonist in the preceding menstrual cycle. Cancellation rates, number of oocytes retrieved, clinical pregnancy rates (PR), and ongoing PRs were similar between the two groups.

UK PubMed Central (United Kingdom)

Epifluorescence images of Ca2+ transients elicited by electrical stimulation of single skeletal muscle fibers were studied with fast imaging techniques that take advantage of the large fluorescence...Full Text Available

International Nuclear Information System (INIS)

Crystallization points of aqueous solution of the systems M(ClO_4)_2-H_2O (M"2 = Mg"2"+, Ca"2"+, Sr"2"+, Ba"2"+), depending on the salt concentration, were identified by visual-polythermal method. Relying on model notions on the structure of the electrolyte solutions, specific features of strontium perchlorate solubility polytherm and concentration dependence of the relative dynamic viscosity of the salt aqueous solutions are discussed

British Library Electronic Table of Contents (United Kingdom)

The present study describes the screening of five lactic acid bacteria (LAB) for use as probiotics based on their competitive adhesion and production of antagonistic substances against some fish pathogens. A reduction of adhesion of all pathogenic strains tested was obtained with three of the LAB strains (Lactococcus lactis subsp. lactis CLFP100, Lactococcus lactis subsp. cremoris CLFP102 and Lactobacillus curvatus CLFP150). With the exception of fish pathogens Flavobacterium psychrophilum and Renibacterium salmoninarum that were not inhibited by LAB strains, production of antagonistic compounds by all tested LAB was observed against at least one of the indicator strains. Based on mucus adhesion, competitive exclusion, and suppression of fish pathogen growth, the selected LAB strains can b...

UK PubMed Central (United Kingdom)

Selective estrogen receptor modulators (SERMs) represent a class with a growing number of compounds that act as either estrogen receptor agonists or antagonists in a tissue-specific manner. This article...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundGlucocorticoids down-regulate cytokine synthesis and suppress inflammatory responses. The glucocorticoid receptor (GR) antagonist RU486 may exacerbate the inflammatory...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundZibotentan (ZD4054) is a specific endothelin A (ET_A) receptor antagonist being investigated for the treatment of prostate cancer. As zibotentan is eliminated...Full Text Available

Science.gov (United States)

PMID:11835026

UK PubMed Central (United Kingdom)

This study addresses the mechanism of transport of the H2-receptor antagonist, cimetidine, by the human placenta. A 4-h recycling perfusion of a single placental cotyledon of normal, term, human placenta...Full Text Available

UK PubMed Central (United Kingdom)

PurposeWe assessed the cardiovascular safety profile of degarelix, a new gonadotropin-releasing hormone antagonist.Materials...Full Text Available

UK PubMed Central (United Kingdom)

The Wistar Kyoto (WKY) rat strain is a putative genetic model of comorbid depression and anxiety. Previous research showing increased κ-opioid receptor (KOR)...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundHistone post-translational modifications are critical for gene expression and cell viability. A broad spectrum of histone lysine residues have been identified in yeast...Full Text Available

UK PubMed Central (United Kingdom)

The tumor suppressor adenomatous polyposis coli (APC) is mutated in the majority of colorectal cancers and is best known for its role as a scaffold in a Wnt-regulated protein complex that determines...Full Text Available

International Nuclear Information System (INIS)

The hypothesis that intracellular Ca"2"+ is an essential component of the intracellular mechanism of insulin action in the adipocyte was evaluated. Cells were loaded with the Ca"2"+ chelator quin-2, by preincubating them with quin-2 AM, the tetrakis(acetoxymethyl) ester of quin-2. Quin-2 loading inhibited insulin-stimulated glucose transport without affecting basal activity. The ability of insulin to stimulate glucose uptake in quin-2-loaded cells could be partially restored by preincubating cells with buffer supplemented with 1.2 mM CaCl_2 and the Ca"2"+ ionophore A23187. These conditions had no effect on basal activity and omission of CaCl_2 from the buffer prevented the restoration of insulin-stimulated glucose uptake by A23187. Quin-2 loading also inhibited insulin-stimulated glucose oxidation and the ability of insulin to inhibit cAMP-stimulated lipolysis ...

British Library Electronic Table of Contents (United Kingdom)

The crystal structure of Ca2RuD6 has been determined by neutron powder diffraction: space group Fm3m, K2PtCl6 structure, as found for other hexahydride salts of group 8 metals with alkaline earth or lanthanide counter ions. No structural phase transition was observed between 340K and 50K. The deuterium nuclear quadrupole coupling constant, 54.7kHz, leads to an ionic character of the Ru-D bond of 76%. The known trends in the behaviour of A2MH6 salts are interpreted in terms of the ionization energies of the cation and the central metal atom.

UK PubMed Central (United Kingdom)

1. The induction of long-term potentiation (LTP) was investigated in the rat dentate gyrus in the presence of ryanodine, an agent which is known to selectively bind to the ryanodine receptor (RyR) Ca2+...Full Text Available

International Nuclear Information System (INIS)

FT-IR spectrum of fulvic acid from wheathered coal of Gongxian is determined using second derivative spectroscopy and the spectroscopic resolution is enhanced. Moreover, FT-IR spectra of the complexes of fulvic acid with Ca"2"+, Ba"2"+, Cu"2"+, Pb"2"+ and UO_2"2"+ under different pH are determined and the nature of the coordination of these complexes is discussed.

UK PubMed Central (United Kingdom)

The design of the time-resolved x-ray diffraction experiments reported in this and an accompanying paper was based on direct measurements of enzyme phosphorylation using [gamma-32P]ATP that were employed...Full Text Available

Science.gov (United States)

Calcium-activated chloride channels (CaCCs) are widely expressed in mammalian tissues, including intestinal epithelia, where they facilitate fluid secretion. Potent, selective CaCC inhibitors have not been available. We established a high-throughput screen for identification of inhibitors of a human intestinal CaCC based on inhibition of ATP/carbachol-stimulated iodide influx in HT-29 cells after lentiviral infection with the yellow fluorescent halide-sensing protein YFP-H148Q/I152L. Screening of 50,000 diverse, drug-like compounds yielded six classes of putative CaCC inhibitors, two of which, 3-acyl-2-aminothiophenes and 5-aryl-2-aminothiazoles, inhibited by >95% iodide influx in HT-29 cells in response to multiple calcium-elevating agonists, including thapsigargin, without inhibition of calcium elevation, calcium-calmodulin kinase II activation, or cystic fibrosis transmembrane conductance regulator chloride channels. These compounds also inhibited ...

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Blood flow changes in the periodontal ligament (PDL) were measured indirectly by monitoring the local clearance of /sup 125/I/sup -/ during electric sympathetic nerve stimulation or close intra-arterial infusions of either noradrenaline (NA) or adrenaline (ADR) before and after administration of phentolamine (PA), phenoxybenzamine (PBZ) or Idazoxan (RX). At the doses used in the present study, PA was the only antagonist that significantly reduced the blood flow decrease seen on activation of sympathetic fibers, although PBZ also reduced this response. Idazoxan, however, did not induce the consistent effect on blood flow decreases seen on sympathetic activation. All three ..cap alpha..-adrenoceptor antagonists almost abolished the effects of exogenously administered NA and ADR. The results suggest the presence of functional post-junctional adrenoceptors of both the ..cap alpha.. 1 and ..cap alpha.. 2 subtypes in the sympathetic regulation of the ...

British Library Electronic Table of Contents (United Kingdom)

Abstract Strains of Pseudomonas syringae are effective in controlling postharvest diseases of citrus fruits, and antagonistic activity has been correlated with in vitro production of lipodepsipeptides. Additionally, biocontrol agents can induce a range of defence mechanisms of resistance in citrus tissue that result in a broad spectrum of metabolic modifications, such as systemic acquired resistance, induced systemic resistance and production of reactive oxygen species. The aim of this study was to evaluate the expression of syringomycin (syrB1) and syringopeptin (sypA) synthetase genes from P.syringae pv. syringae biocontrol strains in vitro on different culture media and in vivo on citrus fruits (Citrus sinensis cv. Tarocco) during the interaction with Penicillium digitatum by quantitati...

International Nuclear Information System (INIS)

The aim of this review is to evaluate the role of inflammatory spine disease in patients with chronic back pain. The contribution of imaging modalities for the diagnostic evaluation of back pain is discussed. A systematic literature search based on the classification of seronegative spondyloarthropathies and rheumatoid arthritis was performed. The results of this search and the experiences in a large collective of rheumatological patients are analyzed. The prevalence of rheumatoid arthritis (1-2%) is comparable to that of spondyloarthropathies (1.9%). The etiology of these entities is not fully elucidated. Magnetic resonance imaging is increasingly used for early detection and surveillance of therapy with TNF-#alpha# antagonists. Bone marrow edema, which is only detectable with MRI, represents an early sign of inflammation. Therapy with TNF-#alpha# antagonists is based on clinical and laboratory criteria, and signs of inflammation in MRI. MRI ...

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In rat adipocyte membranes, both beta-adrenergic agonists and beta-adrenergic antagonists competed with (--)(/sup 3/H)dihydroalprenolol for high affinity (KD 2-4 nM) and low capacity binding sites. The antagonists but not the agonists competed with (--)(/sup 3/H)dihydroalprenolol for lower affinity and higher capacity sites. The present studies were performed in order to characterize the adipocyte beta-adrenergic receptor and distinguish it from low affinity, higher capacity sites which were heat-labile and not stereoselective. When isoproterenol was used to define the nonspecific binding, saturation studies showed a single binding site with a capacity of approximately 100 fmol/mg membrane protein (corresponding to approximately 50,000 sites/adipocyte). Binding was saturated by 10 nM (--)(/sup 3/H)dihydroalprenolol. Approximate KD's of 204 nM were observed. Kinetic analysis of (--)(/sup 3/H)dihydroalprenolol binding provided an ...

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The pharmacology of the alpha-2 adrenoceptor of the human adipocyte was improved by using some new alpha-2 antagonists from different chemical families (imidazolines, benzazepines and benzofuroquinolizines) in biological and binding assays. Moreover, investigations were also carried out to define the binding properties of a new imidazolinic antagonist, RX821002 (2-(2-methoxy-1,4-benzodioxan-2yl)-2-imidazoline), which could be a potential radioligand. (3H)RX821002 binding was very rapid and reversible. Saturation isotherms indicated that (3H)RX821002 labeled, with high affinity, a homogeneous population of noninteracting binding sites with a mean Kd of 0.98 +/- 0.05 nM (n = 6). The binding of (3H)RX821002 on the human fat cell alpha-2 adrenoceptor displayed a specificity which is strictly similar to that obtained with (3H)rauwolscine and which is classical for an alpha-2 A adrenoceptor. The binding parameters of (3H)RX821002 were compared with ...

UK PubMed Central (United Kingdom)

Dopamine (DA) D3 and D2 receptor mechanisms are implicated in cocaine's abuse-related behavioral effects, but the relative contribution of the two receptor subtypes is only partially characterized....Full Text Available

International Nuclear Information System (INIS)

Aminophenpyramine, a derivative of mepyramine (pyrilamine), a typical antagonists of histamine at its H_1 receptor was synthesized and converted into ["1"2"5I]iodoazidophenpyramine, a potential photoaffinity probe for the H_1 receptor. In the dark, reversible binding of this probe to cerebellar membranes occurred with a K/sub d/ of 1.2 x 10"-"1"1 M and a B/sub max/ of 240 fmol/mg of protein and was inhibited by various H_1-receptor antagonists with the expected potencies. These features establish the compound as one of the most potent H_1-receptor antagonists known so far. Upon IV irradiation, 5% of the bound radioactivity was covalently incorporated into cerebellar membrane polypeptides as shown by standard NaDodSO_4/PAGE. Two bands of 47 and 56 kDa were consistently labeled, labeling being prevented by various H_1-receptor antagonists with the expected potencies and stereoselectivity. In the presence ...

UK PubMed Central (United Kingdom)

BackgroundThe ability of catecholamines to stimulate bacterial growth was first demonstrated just over a decade ago. Little is still known however, concerning the nature of the putative...Full Text Available

Scientific Electronic Library Online (English)

Abstract in english Cell death is preceded by severe disruption of inorganic ion homeostasis. Seconds to minutes after an injury, calcium, protons, sodium, potassium and chloride are exchanged between the cell and its environment. Simultaneously, ions are shifted between membrane compartments inside the cell, whereby mitochondria and endoplasmic reticulum play a crucial role. Depending of the type and severity of injury, two mutually exclusive metastable states can be reached, which predict (more) the final outcome. Cells characterized by large increases in cytosolic [Ca2+], [Na+]; and [Mg2+] swell and die by necrosis; alternatively, cells characterized by high [H+]and low [K+], with normal [Na+] and normal to moderate [Ca2+] increases die by apoptosis. The levels of these ions represent central determinants in signaling events leading to cell death. Their movements are explained mechanistically by ...

International Nuclear Information System (INIS)

The purpose of the present study was to examine the in vitro effects of low-dose cadmium (Cd) on developing cortical cells. The cortical cells removed from fetuses (embryonic day 15) were treated with 10 nM of Cd for 24 h. The effects of Cd on dendritic and synaptic development were immunocytochemically observed with anti-microtubule associated protein-2 (MAP2) and anti-synapsin I antibodies, respectively. Administration of Cd suppressed dendritic as well as synaptic development at 10 nM. By two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometric (LC/MS/MS) analysis, we identified three proteins with different expression after Cd-treatment; dihydropyrimidinase-related protein 2 (DRP-2/CRMP-2), 14-3-3-epsillon and calmodulin (CaM). Though the number of identified proteins was small, these proteins are known to be involved in neuronal development. The present study demonstrated the morphological effects as well as affected proteins in ...

British Library Electronic Table of Contents (United Kingdom)

A new coumarin-based sensor molecule (L1) has been synthesized and this was found to bind calcium and magnesium ions more effectively as compared to other alkali/alkaline earth/lanthanide and certain transition metal ions. A significant enhancement in fluorescence intensity was observed on binding to Ca2+ and Mg2+ ions; while a minor quenching was observed for weakly bound Hg2+, Ni2+, Fe3+, and Co2+ ions. PET process, coupled with the ICT process, is proposed to explain the observed spectral response.

Science.gov (United States)

Myostatin is a member of the transforming growth factor-{beta} (TGF-{beta}) family and a strong negative regulator of muscle growth. Here, we present the crystal structure of myostatin in complex with the antagonist follistatin 288 (Fst288). We find that the prehelix region of myostatin very closely resembles that of TGF-{beta} class members and that this region alone can be swapped into activin A to confer signalling through the non-canonical type I receptor Alk5. Furthermore, the N-terminal domain of Fst288 undergoes conformational rearrangements to bind myostatin and likely acts as a site of specificity for the antagonist. In addition, a unique continuous electropositive surface is created when myostatin binds Fst288, which significantly increases the affinity for heparin. This translates into stronger interactions with the cell surface and enhanced myostatin degradation in the presence of either Fst288 or Fst315. Overall, we have identified ...

Science.gov (United States)

Endoreduplication represents a cell cycle variant during which multiple rounds of DNA replication occur without subsequent chromosome separation and cytokinesis, resulting into a cellular increase of the DNA content. Although the DNA ploidy level of cells is controlled by external stimuli such as light, currently limited knowledge is available on how environmental signals regulate the endoreduplication cycle at the molecular level. Previously, we have demonstrated that the conversion from the mitotic cell cycle into an endoreduplication cycle is mediated by the atypical E2F transcription factor DEL1 that operates as a repressor of endocycle onset. Here, we identified DEL1 as a transcriptional target of the classical E2Fb and E2Fc transcription factors that antagonistically control DEL1 transcript levels through competition for a single E2F cis-acting binding site. Correspondingly with the reported opposite effect of light on the E2Fb and E2Fc protein levels, the ...

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Evolutionary theory holds that aging is a consequence of the declining force of natural selection with age. We discuss here the evidence that among the causes of aging in complex multicellular organisms, such as mammals, is the antagonistically pleiotropic effects of the cellular responses that protect the organism from cancer. Cancer is relatively rare in young mammals, owing in large measure to the activity of tumor suppressor mechanisms. These mechanisms either protect the genome from damage and/or mutations, or they elicit cellular responses--apoptosis or senescence--that eliminate or prevent the proliferation of somatic cells at risk for neoplastic transformation.We focus here on the senescence response, reviewing its causes, regulation and effects. In addition, we describe recent data that support the idea that both senescence and apoptosis may indeed be the double-edged swords predicted by the evolutionary hypothesis of antagonistic ...

Science.gov (United States)

The widespread use of tobacco and alcohol among adolescents might be related to the ability of nicotine and ethanol to facilitate social interactions. To investigate the neurobehavioral mechanisms underlying the prosocial effects of nicotine and ethanol, we focused on social play behavior, the most characteristic social activity in adolescent rats. Social play behavior is rewarding, and it is modulated through opioid, cannabinoid and dopaminergic neurotransmission, which are also involved in the reinforcing properties of nicotine and ethanol. We found that nicotine and ethanol increased social play, without affecting locomotion or social exploration. Their effects depended on the level of social activity of the partner, and were comparable in familiar and unfamiliar environments. At doses that increased social play, nicotine and ethanol had no anxiolytic effects in the elevated plus-maze. By contrast, the prototypical anxiolytic drug diazepam reduced social play at doses that reduced ...

International Nuclear Information System (INIS)

Introduction: Development of agonist positron emission tomography (PET) radioligands for the 5-HT neurotransmitter system is an important target to enable the understanding of human 5-HT function in vivo. ["1"1C]CUMI-101, proposed as the first 5-HT_1_A receptor agonist PET ligand, has been reported to behave as a potent 5-HT_1_A agonist in a cellular system stably expressing human recombinant 5-HT_1_A receptors. In this study, we investigate the agonist properties of CUMI-101 in rat brain tissue. Methods: ["3"5S]-GTP#gamma#S binding studies were used to determine receptor function in HEK (human embryonic kidney) 293 cells transfected with human recombinant 5-HT_1_A receptors and in rat cortex and rat hippocampal tissue, following administration of CUMI-101 and standard 5-HT1A antagonists (5-HT, 5-CT and 8-OH-DPAT). Results: CUMI-101 behaved as an agonist at human recombinant 5-HT_1_A receptors (pEC_5_0 9.2). However, CUMI-101 did not show agonist activity in either ...

British Library Electronic Table of Contents (United Kingdom)

Mineral carbonation is based on the reaction of carbon dioxide with metal-oxide bearing minerals, usually containing magnesium or calcium silicate, to form hardly soluble carbonates and other solid byproducts. The concept is based on acceleration of the naturally occurring rock weathering process. In the present work the calcium silicate is present in the mineral, wollastonite. To accelerate the process and make it potentially useful for practical applications, mineral carbonation is conducted here using an indirect two-step route in which the reactive component (Ca^2^+ ions in considered case) is first extracted from the mineral matrix and afterwards carbonated. Two solid byproducts are formed in this process: silica in the extraction step and calcium carbonate in the carbonation step. In...

Science.gov (United States)

A factor which agglutinated the spores of Ceratocystis fimbriata in the presence of Ca2+ was purified from sweet potato (Ipomea batatas Lam cv. Norin[1]) root. Element composition of the purified factor was as follows; analysis found: C (29.8%), H (3.97%), O (65.34%), N (0.81%): calculated for C43H69O70N1: C (30.02%), H (4.01%), O (65.15%), N (0.81%). The factor was mainly composed of galacturonic acid (53% of dry weight) and contained arabinose, fucose, and unidentified component as minor components. The factor also agglutinated A-, B-, AB-, and O types of human erythrocytes to almost the same degree in the presence of Ca2+. The differential spore-agglutinating activity of the factor depended on the pH of the assay medium; it agglutinated similarly the germinated spores of sweet potato and coffee strains at pH 7.5 and 5.5, whereas it displayed a distinct differential agglutinating activity at pH 6.5. ...

Energy Technology Data Exchange (ETDEWEB)

Investigations of cadmium toxicity to microorganisms are now more concerned with the interactions of cadmium with different environmental factors and other metals. The interactions are complex and have not been thoroughly studied yet. Metal interactions may assume the form of synergism characterized by increase in toxicity, but also of antagonism in which one metal reduces the toxicity of another. Apart from cadmium interactions with such toxic metals as mercury and lead, interactions of cadmium with the essential trace elements seem to be very interesting because it has been assumed that algal cells take up cadmium by the system transporting these elements. A previous study showed that cadmium transport into Stichococcus bacillaris cells was inhibited by Mn/sup 2 +/ ions. Thus, it can be supported that there exist some possibilities of using those ions antagonistic to cadmium as counterposition. Showing those possibilities was the aim of the present paper.

Energy Technology Data Exchange (ETDEWEB)

'The overall objective of the basic research grant is to characterize the potential of common hydrocarbon contaminants in ecosystems to act as endocrine disruptors. The three major lines of research include (1) a biotechnology based screening system to identify potential hormone mimics and antagonists; (2) an animal screening system to identify biomarkers of endocrine effects. and (3) a literature review to identify compounds at a variety of DOE sites that need to be examined for endocrine disrupting effects. By relating results obtained from this research project to contamination problems at various DOE sites. CBR will provide data and information on endocrine disrupting contaminants to DOE for consideration in risk analyses for determining clean-up levels and priorities needed at the sites.'

Energy Technology Data Exchange (ETDEWEB)

A detailed chemical kinetic model to describe the autoignition of gasoline surrogate fuels is presented consisting of the fuels iso-octane, n-heptane, toluene, diisobutylene and ethanol. Model predictions have been compared with shock tube ignition delay time data for surrogates of gasoline over practical ranges of temperature and pressure, and the model has been found to be sensitive to both changes in temperature and pressure. Moreover, the model can qualitatively predict the observed synergistic and antagonistic non-linear blending behaviour in motor octane number (MON) for different combinations of primary reference fuels (PRFs) and non-PRFs by correlating calculated autoignition delay times from peak pressures and temperatures in the MON test to experimental MON values. The reasons for the blending behaviour are interpreted in terms autoignition chemistry. 37 refs., 11 figs., 4 tabs.

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Effects of 2450-MHz circularly polarized microwave irradiation on central nervous system functions were studied. Pulsed (microsecond, 500 pps) microwaves decreased high-affinity sodium-dependent choline uptake in the hippocampus and frontal cortex of the rat. The effect on hippocampal choline uptake was blocked by pretreatment with narcotic antagonists. Continuous-wave microwaves of the same power density decreased choline uptake in the frontal cortex only. Furthermore, it was found that the effects of pulsed microwaves on central cholinergic activity are classically conditionable to cues in the exposure environment. The hypothesis that some of the neurological effects of pulsed microwave irradiation are caused by its effect on the auditory system was investigated. Effects of pink noise and pulsed microwaves were compared.

DEFF Research Database (Denmark)

Aldosterone has been suggested to elicit vessel contraction via a nongenomic mechanism. We tested this proposal in microdissected, perfused rabbit renal afferent arterioles. Aldosterone had no effect on internal diameter in concentrations from 10(-10) to 10(-5) mol/L, but aldosterone abolished the ability of 100 mmol/L KCl to induce vascular contraction. The inhibitory effect of aldosterone was observed from 1 pmol/L. The inhibitory effect was significant after 5 minutes and maximal after 20 minutes and was fully reversible. Actinomycin D (10(-6) mol/L) prolonged the effect of aldosterone. The effect was abolished by the mineralocorticoid receptor antagonist spironolactone (10(-7) mol/L) but not by the glucocorticoid receptor antagonist mifepristone (10(-6) mol/L). The K+-mediated increase of intracellular calcium concentration in afferent arterioles was not affected by aldosterone. Mineralocorticoid receptor was detected by reverse ...

Science.gov (United States)

The purpose of this study was to examine arachidonic acid (AA) metabolism and to characterize the type of adrenergic receptor (AR) involved in the production of the major metabolite of this fatty acid. ({sup 14}C)AA was incubated with GPT-rings and the radiolabelled products were extracted and separated by TLC method. The medium was also assayed for radiolabelled immunoreactive PG's (iPG's) and leukotrienes (LT) B4 and C4 by RIA or Enzyme immunoassay (EIA) after exposure to various AR agonists. ({sup 14}C)AA was incorporated into GPT-rings and metabolized mainly into iPGE2 and smaller amounts into PGF2{alpha}. Trace amounts of PGD2 and 6-keto-PGF1{alpha} but not LTB4 or LTC4 were detected by RIA and/or EIA. Incubation of GPT rings for 15 minutes with isoproterenol and salbutamol resulted in a significant increase of PGE2 synthesis (optimum conc: 10{sup {minus}7}, 10{sup {minus}7}M respectively). In contrast, dobutamine, norepinephrine, phenylnephrine and xylazine (up ...

Science.gov (United States)

It is hypothesized that systemic ??-noradrenergic antagonists may interfere with the transmission of sensory stimulation, particularly vaginal--cervical stimulation (VCS), which is crucial for reproductive functioning. To determine if ??-noradrenergic transmission receptor activity is necessary for transmission of sensory information important for VCS-dependent events, we conducted an experiment using prazosin, a ??-noradrenergic receptor antagonist. First, three doses of prazosin (1.0, 0.5 or 0.1 mg/kg) or the 10% ETOH in sesame oil vehicle were administered i.p. and sexual receptivity was assessed 30 min later in ovariectomized, hormone-treated female rats. The 1 mg/kg dose of prazosin significantly inhibited lordosis quotients and lordosis ratings. This dose of prazosin (1.0 mg/kg) was then administered 30 min prior to VCS or control scapular stimulation (CSS) and Fos-IR was examined in the posterodorsal medial amygdala (MeaPD), the medial ...

International Nuclear Information System (INIS)

The local environment of Ca dopants in barium titanate, BaTiO_3, is investigated by Ca K-edge X-ray absorption near-edge structure (XANES) spectroscopy. In conjunction with experiments, first-principles calculations by two methods are systematically made. The projector-augmented wave (PAW) method is used to optimize the local structure and obtain the formation energy. The augmented plane wave plus local orbitals method is adopted to obtain theoretical XANES spectra. A comparison between experimental and theoretical XANES spectra shows that Ca dopants are located at the Ba"2"+ sites forming Ca"2"+. Formation energy calculations of Ca doped BaTiO_3 by the PAW method also give the same results. The Ca atom in BaTiO_3 is off-centering in comparison with the Ba site in BaTiO_3. The off-centering of Ca atom is newly revealed by the combination of XANES spectroscopy and first-principles DFT calculations.

British Library Electronic Table of Contents (United Kingdom)

The biosorption of phosphate from aqueous solutions using Fe(III)-treated Staphylococus xylosus cells was investigated. Langmuir and Freundlich isotherm models were applied to describe the adsorption equilibrium and found that Langmuir isotherm model fitted the equilibrium data better than Freundlich isotherm model. The biosorption capacity of Fe(III)-treated biomass for phosphate was found to be 70.92mg/g at optimum conditions of pH 3.0, biomass concentration 0.5g/L and equilibrium phosphate-biomass time 60min respectively. The sorption efficiency at initial phosphate concentration of 50mg/L was not influenced upon addition of SO4^2^-, Cl^-, CO3^2^-, NO3^-, Mg^2^+ and Ca^2^+ ions from 0 to 800mg/L, whereas under the same conditions, phosphate sorption was increased with increase in concen...

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Since chlordecone (Kepone, CD) interferes with cardiac Na{sup +} ion translocases, we have studied CD effects on cardiac SR calcium pump activity. SR was isolated from heart ventricles of male Sprague-Dawley rats. Cardiac SR Ca{sup 2+}-ATPase, {sup 45}Ca-uptake and cAMP as well as calmodulin (CaM) dependent protein phosphorylation were measured. Ca{sup 2+}-ATPase was differentiated into low affinity and high affinity forms by measuring the activity using 50 and 0.7 {mu}M free Ca{sup 2+} respectively. CD in vitro inhibited {sup 45}Ca-uptake by SR in a concentration dependent manner with an IC50 value of 7 {mu}M and SR {sup 45}Ca-uptake was totally inhibited at 20-30 {mu}M CD. In agreement with this, both high affinity and low affinity Ca{sup 2+}-ATPases, which are involved in Ca{sup 2+} transport across membranes, were also inhibited by CD in a concentration dependent manner with IC50 values of 0.7 and 3.2 {mu}M respectively. Both Ca{sup 2+}-ATPase and {sup ...

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The subfornical organ is a major receptor area for one of the principal stimuli of thirst, the octapeptide, angiotensin II. In conscious water-sated rats, the authors examined the effects of intravenous infusion of angiotensin II on the rate of glucose utilization in the subfornical organ and in structures anatomically and functionally connected with it. Angiotensin II produced pressor and drinking responses and increased glucose utilization selectively in the subfornical organ and pituitary neural lobe and in no other brain structure. Treatment with the angiotensin II antagonist, sar1-leu8-angiotensin II, before intravenous administration of angiotensin II prevented metabolic stimulation of the subfornical organ and neural lobe. Captopril, an inhibitor of angiotensin-converting enzyme, reduced subfornical organ glucose metabolism to a level similar to that found in control animals. These results demonstrate that peripheral angiotensin II stimulates glucose ...

British Library Electronic Table of Contents (United Kingdom)

Aims: Serotonin (5-hydroxytryptamine 3; 5-HT3) receptors are involved in chemotherapy-induced nausea and vomiting (CINV), and 5-HT3 antagonists are part of the `gold standard' antiemetic treatment during chemotherapy. We investigated the correlation of common variants in 5-HT3 receptor subunit genes with the occurrence of CINV. Materials & methods: A total of 110 previously characterized chemotherapy-naive women with primary breast cancer treated with anthracycline-containing chemotherapy served as a study group for mutational analysis by direct sequencing. Eight common SNPs in the 5-HT3 receptor genes, HTR3A, HTR3B, HTR3D and HTR3E, were selected for association analysis. Results: A nonsynonymous variant in HTR3D, p.G36A (rs6443930), was found to be over-represented in nonresponders, assu...

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Methylxanthines and their derivatives are antagonists at cell surface adenosine receptors. They report here a systematic study of xanthine structure-activity relationships which compares potency at two adenosine receptor subtypes, R/sub a/ and R/sub i/. Adenylate cyclase stimulation (R/sub a/ in platelet membranes) and inhibition (R/sub i/ in adipocyte membranes) were used as models of receptor activation. K/sub i/ values were obtained by Schild analysis. The orders of potency of the xanthines to attenuate the effects of adenosine analogues were similar to those previously reported. Earlier work utilizing radioligand binding (R/sub i/ and (/sup 3/H) cAMP formation (R/sub a/) claimed that IIX and PACPX are at least 10 and 400 fold, respectively, more potent at R/sub i/ than at R/sub a/. However, in their assays which utilize modulation of receptor-coupled adenylate cyclase, the xanthines show little specificity for either adenosine receptor subtype.

British Library Electronic Table of Contents (United Kingdom)

PurposeWe investigated the efficacy and safety of degarelix treatment and the effects of switching from leuprolide to degarelix in an ongoing extension study with a median 27.5-month followup of a pivotal 1-year prostate cancer trial. Materials and MethodsPatients who completed a 1-year pivotal phase III trial continued on the same monthly degarelix maintenance dose (160 or 80 mg in 125 each), or were re-randomized from leuprolide 7.5 mg to degarelix 240/80 mg (69) or 240/160 mg (65). Data are shown on the approved degarelix 240/80 mg dose. The primary end point was safety/tolerability and the secondary end points were testosterone, prostate specific antigen, luteinizing hormone and follicle-stimulating hormone responses, and prostate specific antigen failure and progression-free survival....

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The maintenance of a balance between cell gain and cell loss is essential for proper liver function. The exact role of aryl hydrocarbon receptor (AhR) in regulating cell proliferation and apoptosis of liver cells remains unclear, since ligand-dependent activation of AhR has been shown to induce cell cycle arrest, proliferation, differentiation or apoptosis, depending on the cellular model used. AhR can directly interact with retinoblastoma protein in hepatic cells, forming protein complexes that can efficiently block cell cycle progression by inducing G1 arrest, or to induce the expression of inhibitors of cyclin-dependent kinases, such as p271. On the other hand, it has been suggested that AhR could play a stimulatory role in cell proliferation, either directly or by mediating a release from contact inhibition. It is now generally accepted that progenitor cells exist in the liver, are activated in various liver diseases and can form a potential target cell population for both tumor ...

International Nuclear Information System (INIS)

Spherical aggregates formed rapidly in culture by re-aggregation of trypsin-dissociated brain cells from the 17-day-old fetal rat. Over about 10 days an initially random distribution of cells evolved into a 3-layered arrangement; cells with characteristics of neurons were found largely in the intermediate layer. The survival of neuronal and glial cell types was evaluated histologically and verified by electron microscopy, which revealed synaptic and myelin structures that rapidly increased in number after 18 days in culture. Levels of norepinephrine (NE) and dopamine (DA) reached peaks of 9.5 and 4.4 ng/mg protein, respectively, at culture day 21. Uptake of ["3H]NE paralleled these amine levels and was blocked by desipramine or pretreatment with either reserpine or 6-OH-DA. Autoradiographs of aggregates labeled with ["3H]NE showed a high density of silver grains over cells, apparently neurons, with branching processes traced for 120 #mu#m. Previously accumulated ["3H]NE was released ...

Science.gov (United States)

Eight phospholipases A2 (PLAs) and four three-finger-toxins (3FTx) from the pooled venom of Bungarus fasciatus (Bf) were previously studied and sequenced, but their expression pattern in individual Bf venom and possible geographic variations remained to be investigated. We herein analyze the individual venom of two Bf specimens from Kolkata (designated as KBf) to address this question. Seven PLAs and five 3FTx were purified from the KBf venoms, and respective cDNAs were cloned from venom glands of one of the snakes. Comparison of their mass and N-terminal sequence revealed that all the PLAs were conserved in both KBf venoms, but that two of their 3FTx isoforms were variable. When comparing the sequences of these KBf-PLAs with those published, only one was found to be identical to that of Bf Vb-2, and the other five were 94-98% identical to those of Bf II, III, Va, VI and XI-2, respectively. Notably, the most abundant PLA isoforms of Bf and KBf venoms contain Pro31 substitution. They ...

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Late Archean (ca. 2.5Ga) porphyritic granites to comprise about 25% of the crystalline rocks of the Wind River uplift. In most localities, they are typical biotite-hornblende granites but on the western margin of the range there is evidence that portions of at least one pluton were emplaced as charnockite. In the Burnt Lake area homogenous charnockite crops out over an area of at least 3km while in the Boulder Creek Canyon, 8km to the S.E. charnockite occurs locally as blotches in porphyritic biotite granite. One sample from Boulder Creek, 15 cm in the longest dimension, shows a complete transition from charnockite to biotite granite. Textures indicate that the transition occurred as subsolidus hydration, with hornblende and biotite replacing augite and orthopyroxene, respectively. Pryoxene geothermometry from this sample yields maximum temperatures of around 900/sup 0/C, with a cooling trend to 600/sup 0/. Fluid inclusion of both CO/sub 2/ (p ...

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Extracellular ATP stimulates transmembrane ion fluxes in the mouse macrophage cell line J774. In the presence of Mg2+, nonhydrolyzable ATP analogs and other purine and pyrimidine nucleotides do not elicit this response, suggesting the presence of a specific receptor for ATP on the macrophage plasma membrane. One candidate for such a receptor is the ecto-ATPase expressed on these cells. We, therefore, investigated the role of this enzyme in ATP-induced /sup 86/Rb+ efflux in J774 cells. The ecto-ATPase had a broad nucleotide specificity and did not hydrolyze extracellular ATP in the absence of divalent cations. /sup 86/Rb+ efflux was not blocked by inhibition of the ecto-ATPase and did not require Ca2+ or Mg2+. In fact, ATP-stimulated /sup 86/Rb+ efflux was inhibited by Mg2+ and correlated with the availability of ATP4- in the medium. In the absence of divalent cations, the slowly hydrolyzable ATP analogs adenosine 5'-(beta, ...

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In the present study, the immunomodulatory effect of {beta}-endorphin ({beta}-E) and shorter pro-opiomelancortin (POMC) fragments was evaluated by assessing their influence on respiratory burst in human polymorphonuclear leukocytes (PMN). The effect of the peptides on phorbol myristate acetate (PMA)-stimulated production of reactive oxygen metabolites was measured in a lucigenin-enhanced chemiluminescence (CL) assay. Both POMC peptides with opiate-like activity and their non-opioid derivatives were tested. With the exception of {alpha}-E, PMA-stimulated respiratory burst was suppressed by all POMC fragments tested. A U-shaped dose-response relation was observed. Doses lower than 10{sup {minus}17}M and higher than 10{sup {minus}8}M were without effect. {beta}-E and dT{beta}E both suppressed PMA-induced oxidative burst in human PMN at physiological concentrations. {gamma}-E and dT{gamma}E proved to be less potent inhibitors, reaching maximal effect at higher concentrations. DE{gamma}E ...

Science.gov (United States)

Anthraquinones are widely present in plant kingdom, and clinically used as laxatives. Environmental contaminants, dioxins, develop various adverse effects through transformation of a cytosolic aryl hydrocarbon receptor (AhR). We investigated the effects of 18 anthraquinones and 7 of their structurally related compounds on transformation of the AhR estimated by its DNA-binding activity in the cell-free system. 1,4-Dihydroxyanthraquinone (quinizarin), 1,5-dihydroxyanthraquinone (anthrarufin), 1,8-dihydroxyanthraquinone (danthron), and 5-hydroxy-1,4-naphthoquinone (juglone) strongly suppressed DNA-binding activity of the AhR induced by 0.1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), with their IC(50) values around 1 muM. On the other hand, anthraquinone, 2,6-dihydroxyanthraquinone (anthraflavic acid), and 2-hydroxy-1,4-naphthalendione (lawsone) showed moderate effects. Quantitative structure-activity relationships analysis demonstrated that hydroxyl groups at C1 or C4 but not C3 ...

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The radioiodination and in vivo evaluation of p-iodocaramiphen a muscarinic antagonist which binds with high affinity to the M[sub 1] receptor subtype in vitro are described. Biodistribution studies in female Fischer rats demonstrated that [[sup 125]I]-piodocaraminphen had significant cerebral localization, but the uptake did not demonstrate specific uptake in those cerebral regions rich in muscarinic receptors, and radioactivity washed out rapidly from the brain. In addition there was no significant blockage of activity when the rats were preinjected with quinuclidinyl benzilate. These results suggest that p-iodocaramiphen is not a good candidate for the in vivo study of M[sub 1] muscarinic receptor populations by SPECT. Because of the widespread interest and expected importance of the availability of large amounts of tungsten-188 required for the tungsten-188/rhenium-188 generator systems, we have investigated the large-scale production of tungsten-188 in the ...

Science.gov (United States)

The epileptogenic and neurodegenerative effects of gamma-dendrotoxin, from Dendroaspis angusticeps, a specific blocker of a non-inactivating, voltage-sensitive K+ channel, were studied after focal injection into one dorsal hippocampus in rats pretreated with CGP040116, a N-methyl-D-aspartate (NMDA) receptor antagonist, and in rats bearing a monolateral surgical lesion of the Schaffer collaterals whose terminals originate from CA3 pyramids and release glutamate in the CA1 hippocampal area. Administration of 35 pmol gamma-dendrotoxin elicited in all of the treated animals (n=8) bilateral EEG discharges and damage to the hippocampal formation. Quantitation of the damage revealed significant bilateral neuronal cell loss in the CA1, CA3 and CA4 pyramidal cell layers. The lowest dose (0.35 pmol; n=4) of the toxin used did not affect EEG activity and failed to cause significant hippocampal cell loss whereas the 3.5 pmol (n=6) dose caused EEG seizures and hippocampal cell ...

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Red light stimulates germination in the spores of Onoclea sensibilis L. Phytochrome is confirmed to be the photoreceptor pigment in the germination response by demonstrating red-far-red photoreversibility. External Ca/sup 2 +/ is required for this response with a threshold at a submicromolar concentration. Red light stimulates an increase in the total concentration of intracellular calcium in the spores as determined by atomic absorption spectroscopy. Subsequent exposure to far-red light inhibits the red light-induced increase in intracellular calcium. The majority of the increase occurs 5 minutes after the onset of irradiation. The calcium-antagonist, La/sup 3 +/ inhibits both germination and the red light-induced increase in intracellular calcium. Using /sup 31/P-nuclear magnetic resonance spectroscopy, the author tested the hypothesis that a sustained increase in intracellular pH contributes to the signal transduction chain. He never detected a red light-induced ...

International Nuclear Information System (INIS)

Serotonin is one of the neurotransmitters found in the brain and mediates brain functions. It is very well known that serotonin related brain abnormalities are exerted mainly via serotonin receptors in a similar manner to other neurotransmitters found in the brain. Recently, it has also been found that serotonin is involved in Alzheimer's disease either directly or indirectly by its actions on serotonergic neurons. To understand and treat the diseases caused by abnormalities in the serotonergic system in the brain, it is certain that its mechanism of function has to be well investigated. So far several 5-HT receptors and receptor subtypes have been well characterized. Moreover, serotonin agonists and antagonists acting on specific receptors are chemically synthesized and are now available for the prevention or treatment of serotonergic related diseases. In recent years, a great demand for developing neuroimaging agents has emerged for the diagnosis of abnormal ...