Abstract：
:The neuroprotective drug riluzole has multiple effects on cellular signaling. We found that riluzole rapidly and reversibly inhibited spontaneous Ca2+ oscillations in both immortalized GnRH-secreting hypothalamic neurons (GT1 cells) and in the prolactin and growth-hormone-secreting GH3 cell line. At lower concentrations (100 nm-5 microM), riluzole reduced the amplitude and frequency of spontaneous Ca2+ oscillations, whereas at higher concentrations it abolished spontaneous Ca2+ signaling. Whole-cell current clamp recordings in GH3 cells revealed that riluzole decreased the action potential frequency, amplitude, and duration. Riluzole inhibited voltage-gated Na+ currents, increased iberiotoxin-sensitive voltage-gated K+ currents, and had no effect on voltage-gated Ca2+ currents in GH3 cells. Riluzole also inhibited voltage-gated Na+ currents and increased voltage-gated K+ channels in GT1 cells. The inhibitory effects of riluzole on Ca2+ signaling were blocked by pretreatment with iberiotoxin in GH3 cells, but only partially reduced by iberiotoxin in GT1 cells. These results indicate that riluzole inhibits Ca2+ signaling primarily by activation of K+ channels in GH3 cells, and also by inhibition of Na+ channels in GT1 cells. Riluzole's inhibition of spontaneous excitability and Ca2+ signaling may be involved in its multiple effects on cellular function in the nervous system.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Beltran-Parrazal L,Charles Adoi
10.1038/sj.bjp.0705491subject
Has Abstractpub_date
2003-11-01 00:00:00pages
881-8issue
5eissn
0007-1188issn
1476-5381pii
sj.bjp.0705491journal_volume
140pub_type
杂志文章abstract：:1 The effects of vinblastine and 6-hydroxydopamine (6-OHDA) on various parameters of adrenergic neurone functions in the rat were examined and compared.2 During the first 12 h after injection of vinblastine, although the concentration of cardiac noradrenaline was unaltered, the turnover rate of the catecholamine in th...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1974.tb08564.x
更新日期：1974-02-01 00:00:00
abstract：:The molecular mechanisms involved in veratridine-induced chromaffin cell death have been explored. We have found that exposure to veratridine (30 microM, 1 h) produces a delayed cellular death that reaches 55% of the cells 24 h after veratridine exposure. This death has the features of apoptosis as DNA fragmentation c...
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journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1982.tb09245.x
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abstract：:In recent years, late-stage clinical drug development that primarily focuses on urogenital targets has centered around four areas of medical need (both unmet need and aiming to improve on existing therapies). These include male sexual dysfunction (MSD), female sexual dysfunction (FSD), prostatic pathology (neoplastic,...
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pub_type： 杂志文章,评审
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abstract：:1. The purpose of the present investigations was to determine the influence of increasing age on the pharmacokinetics and pharmacodynamics of midazolam in male BN/BiRij rats as an animal model of aging. 2. Midazolam was administered intravenously at a dose of 2.5 mg kg-1 and its pharmacokinetics were determined on the...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb14482.x
更新日期：1992-09-01 00:00:00
abstract：:Leukotriene B4 (LTB4) is a potent leukocyte chemoattractant, acting on specific receptors, BLT receptors. The aim of this study was to examine the mechanism of action of LTB4 in the guinea-pig lung, using strips of lung parenchyma (GPLP), spirals of trachea (GPT) and bronchus (GPB) and rings of pulmonary artery (GPPA)...
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doi：10.1038/sj.bjp.0705641
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb14758.x
更新日期：1994-02-01 00:00:00
abstract：:The effects of aconitine, an Aconitum alkaloid, on spontaneous inhibitory and excitatory postsynaptic currents (IPSCs and EPSCs respectively) were investigated in the mechanically dissociated rat ventromedial hypothalamic (VMH) neurons in which native presynaptic nerve terminals remained intact. Under current-clamp co...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704517
更新日期：2002-02-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb08777.x
更新日期：1982-01-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702307
更新日期：1999-01-01 00:00:00
abstract：:1. CS-747 is a novel thienopyridine-type platelet ADP inhibitor which lacks in vitro activity. This study examined pharmacological profiles of R-99224, a hepatic metabolite of CS-747. 2. R-99224 produced a concentration-dependent inhibition of in vitro platelet aggregation in washed human platelets (0.03 - 1 microg ml...
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pub_type： 杂志文章
doi：10.1038/sj.bjp.0703761
更新日期：2001-01-01 00:00:00
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pub_type： 杂志文章
doi：10.1038/sj.bjp.0707138
更新日期：2007-03-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13989.x
更新日期：1993-12-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Intestinal mucositis is a common side-effect of irinotecan-based cancer chemotherapy regimens. This mucositis is associated with cytokine activation and NO synthesis. Production of IL-18 is up-regulated in patients suffering from inflammatory bowel disease. Therefore, we have investigated the rol...
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pub_type： 杂志文章
doi：10.1111/bph.12584
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11996.x
更新日期：1989-06-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706655
更新日期：2006-03-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705829
更新日期：2004-06-01 00:00:00
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pub_type： 评论,杂志文章
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pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13916.x
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pub_type： 杂志文章,评审
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更新日期：2008-03-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1978.tb07779.x
更新日期：1978-05-01 00:00:00
abstract：:Experiments were undertaken to determine whether the site of the hypoglycaemic action of 5-hydroxytryptophan (5-HTP), a direct precursor of 5-hydroxytryptamine (5-HT), was in the central nervous system or in the liver. The fall in blood glucose followed the rapid increase in the amount of 5-HT both in the brain and li...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb10553.x
更新日期：1985-07-01 00:00:00
abstract：:The opioid receptors are key targets in the treatment of acute and chronic pain, and the development of novel analgesics with reduced side effects is crucial in the search for more effective medications. The crystal structures of opioid receptors have provided a wealth of knowledge on many aspects of opioid receptor p...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.13774
更新日期：2018-07-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703963
更新日期：2001-04-01 00:00:00
abstract：:The effects of infusions of eicosapentaenoic acid (EPA) (6 X 10(-8) mol min-1 and 15 X 10(-8) mol min-1) on the coronary constriction and the release of immunoreactive sulphidopeptide-leukotrienes (SP-LT), thromboxane B2(TXB2) and 6-keto-prostaglandin F1 alpha (PGF1 alpha) from perfused anaphylactic guinea-pig hearts ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb08961.x
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abstract：:1--Responses (relaxation) to the beta-adrenoceptor agonists, isoprenaline, fenoterol or noradrenaline, were obtained on cat tracheal preparations contracted with a submaximal concentration of carbachol (0.5 microM). 2--The relative potencies of isoprenaline: fenoterol: noradrenaline were 100:8.1:10.7. From this, it wa...
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pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb09406.x
更新日期：1983-02-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Selective oestrogen receptor (ER) modulators (SERMs) are of great value in the treatment of breast cancer and osteoporosis. The aim of this study was to characterize pharmacologically a new class of SERMs synthesized based on the core structure of raloxifene. EXPERIMENTAL APPROACH:Competitive re...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706960
更新日期：2007-01-01 00:00:00
abstract：:Bradykinin, angiotensin II, arginine vasopressin (AVP) or des-amino-D-arginine vasopressin (DDAVP) were administered by intravenous infusion to 10 healthy men. The concentration of 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha), the stable hydrolysis product of prostacyclin (PGI2), was measured in plasma using gas ch...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb10177.x
更新日期：1986-01-01 00:00:00
abstract：:AM-36 is a novel neuroprotective agent incorporating both antioxidant and Na(+) channel blocking actions. In cerebral ischaemia, loss of cellular ion homeostasis due to Na(+) channel activation, together with increased reactive oxygen species (ROS) production, are thought to contribute to neuronal death. Since neurona...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704018
更新日期：2001-04-01 00:00:00
abstract：:1 The isolated perfused ear of the rabbit connected to the body only by its nerve, was used to investigate the influence of prostaglandin F2alpha on the algesic effect of bradykinin and acetylcholine. 2 Bradykinin and acetylcholine, following intra-arterial injection into the isolated perfused ear elicited a dose-rela...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1977.tb08390.x
更新日期：1977-03-01 00:00:00
