Abstract：
:In addition to its well-known interaction with ionotropic and metabotropic receptors, glutamate may, at high concentrations, interfere with a cystine-glutamate antiport designated as Xc- and lead to a significant decrease in cystine uptake and intracellular glutathione level. These effects, in turn, may induce death in various cellular bodies including astrocytes, rat glioma cells and cortical neurons in culture. In the present paper we demonstrate that the toxicity evoked by glutamate in a neuronal-like model is indeed related to the metabolism of glutathione since glutamate toxicity is preceded by a significant depletion of intracellular glutathione and is abolished in the presence of precursors of glutathione synthesis such as cystine and N-acetylcysteine. It also appears that prolonged incubation in cystine-free medium leads to cell detachment and death, a phenomenon which is progressively abolished in the presence of increasing concentrations of cystine. In addition, buthionine sulfoximine, a known inhibitor of glutathione synthesis, also induces cell lysis with a time-course very similar to that of glutamate. However, depletion of glutathione is probably not sufficient to trigger the death signal since cycloheximide, which inhibits the toxic effect of both glutamate and buthionine sulfoximine, does not block the decrease in cellular glutathione content induced by these drugs. Our results therefore confirm that oxidative stress and intracellular glutathione depletion are able to trigger programmed cell death in neuronal-like cells, although the exact nature of the death mechanisms remains largely unknown.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Froissard P,Monrocq H,Duval Ddoi
10.1016/s0014-2999(97)00155-6subject
Has Abstractpub_date
1997-05-12 00:00:00pages
93-9issue
1eissn
0014-2999issn
1879-0712pii
S0014-2999(97)00155-6journal_volume
326pub_type
杂志文章abstract：:Sulfonylurea drugs exert their insulinotropic action by inhibiting ATP-sensitive potassium channels in the pancreas. However, these channels are also expressed in myocardial and vascular smooth muscle, implicating possible detrimental cardiovascular effects. Aim of the present study was to investigate the inhibitory p...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.02.006
更新日期：2012-04-15 00:00:00
abstract：:In myopathic BIO 8262-hamsters beta1-adrenergic stimulation of cardiac adenylyl cyclase has been found to be markedly reduced compared to that of healthy controls. In order to test the hypothesis that the functional uncoupling of beta1-adrenoceptors in diseased hamster hearts is due to agonist-dependent desensitizatio...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01200-4
更新日期：1997-09-10 00:00:00
abstract：:We have developed an isolated spinal cord-skin preparation of the newborn rat. The spinal cord together with a piece of skin connected to the cord by the saphenous nerve was isolated from 1- to 4-day-old rats and separately superfused with artificial cerebrospinal fluid in two neighbouring chambers. Potentials were re...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90737-o
更新日期：1992-09-22 00:00:00
abstract：:Nicotine produced antinociception in mice which was antagonized noncompetitively by naloxone. In addition, at significantly lower doses, nicotine noncompetitively antagonized morphine-induced antinociception. A speculative suggestion regarding the opiatergic and anti-opiatergic actions of nicotine is that it significa...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0926-6917(93)90009-f
更新日期：1993-12-01 00:00:00
abstract：:Beta-lactoglobulin (BLG)-derived peptides may facilitate oral tolerance to whey and prevent cow's milk allergy (CMA). Loading of BLG-peptides in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Pep-NP) may improve this. Here we studied the uptake of NP and the capacity of NP and Pep-NP to activate bone marrow dendr...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2017.10.051
更新日期：2018-01-05 00:00:00
abstract：:The binding of [3H]LSD to serotonergic sites in human brain was studied. The pharmacological profile of [3H]LSD binding in frontal cortex differed to that in hippocampus. Analysis of the inhibition of [3H]LSD binding by serotonin and spiperone was consistent with the presence of two binding sites, which differed in ph...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(82)90555-6
更新日期：1982-08-13 00:00:00
abstract：:The vascular response to most neurotransmitters of different vascular beds is altered under hypertensive condition. The modulatory effect of genetic pulmonary arterial hypertension on histamine responses is not known. The present study was undertaken to evaluate the modulatory effect of enzymatic degradation (via hist...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(03)01759-x
更新日期：2003-05-30 00:00:00
abstract：:Animal studies reveal that diverse environmental stimuli that generate anxiety-like behaviors also induce antinociception; conversely, clinical data show that pain perception is reduced under anxiolysis. This study was conducted to investigate the influence of pharmacologically induced-anxiety on nociception and antin...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2006.06.060
更新日期：2006-10-10 00:00:00
abstract：:This study examined the role of dopamine systems in tolerance to caffeine-induced stimulation of motor activity in the rat. Selective dopamine D1 and D2 receptor agonists were tested alone and combined in rats receiving caffeine chronically by a method of scheduled access to a caffeine solution or in control rats rece...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)90029-9
更新日期：1994-09-01 00:00:00
abstract：:In normotensive rats, we have previously demonstrated a role of brain mineralocorticoid receptors in blood pressure and renal function control. In the present study, the coordinate cardiovascular and renal effects of brain mineralocorticoid receptor blockade were examined by intracerebroventricular (i.c.v.) administra...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01586-2
更新日期：2002-02-02 00:00:00
abstract：:The NMDA receptor is coupled to a cation-selective ion channel, which has been implicated in important brain functions such as long-term potentiation and burst firing, and in neuronal death associated with stroke and epilepsy. We have investigated the binding properties of [3H]MK-801, which binds selectively to the op...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(93)90102-f
更新日期：1993-05-15 00:00:00
abstract：:Dysfunction of the innate immune system has been reported to cause intestinal inflammation. Vitamin D3 is known to be an important immune system regulator and exerts anti-inflammatory effects. We investigated in vitro effects of vitamin D3 and its derivatives on the innate immune system in HT-29 cells, a line of human...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.09.014
更新日期：2013-12-05 00:00:00
abstract：:To evaluate the cardiac effect of an inhibitor of angiotensin-converting enzyme, the effect of intracoronary (i.c.) captopril on coronary blood flow and regional myocardial function was examined in the anesthetized open-chest dog. Blood flow of the left circumflex coronary artery (LCX), left ventricular pressure (LVP)...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(85)90023-8
更新日期：1985-03-26 00:00:00
abstract：:Levonorgestrel (13beta-ethyl-17alpha-ethynyl-17beta-hydroxy-4-gonen-3-one), a potent contraceptive progestin stimulates growth and proliferation of cultured breast cancer cells through a receptor-mediated mechanism, even though levonorgestrel does not bind to the oestrogen receptor (ER). To assess whether the oestroge...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01263-8
更新日期：2001-09-14 00:00:00
abstract：:The actions of 5-hydroxytryptamine have been studied in the chick biventer cervicis nerve--muscle preparation. At concentrations between 2.5 X 10(-3) and 3.7 X 10(-3) M, 5HT produced a transient increase in responses to indirect stimulation, but not to direct stimulation. At higher concentrations, 5HT produced a rever...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(77)90095-4
更新日期：1977-07-15 00:00:00
abstract：:The action of calcitonin gene-related peptide (CGRP) on the vasodepressor response to adenosine was investigated in anesthetized rats. I.v. bolus injections of adenosine (1-100 microg/kg), acetylcholine (0.05-0.4 microg/kg), isoproterenol (1-30 ng/kg), nitroglycerin (0.3-10 microg/kg) and diltiazem (10-300 microg/kg) ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01566-5
更新日期：1998-03-05 00:00:00
abstract：:GABAA and GABAC receptors were studied on cultured or freshly isolated rat retinal bipolar cells. The cells displayed GABA-induced whole-cell currents, which were only partially blocked by high concentrations (100 microM) of the GABAA receptor antagonist bicuculline. The bicuculline-resistant (GABAC) component was ins...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(94)90014-0
更新日期：1994-12-15 00:00:00
abstract：:Angiotensin-converting enzymes, ACE and ACE2, are key members of renin angiotensin system. Activation of ACE2/Ang-(1-7) pathway enhances cardiovascular protective functions of bone marrow-derived stem/progenitor cells. The current study evaluated the selectivity of ACE2 inhibitors, MLN-4760 and DX-600, and ACE and ACE...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2016.01.007
更新日期：2016-03-05 00:00:00
abstract：:Chemopreventive non-steroidal anti-inflammatory drugs (NSAIDs) exhibit diverse pharmacological and biological activities mainly through their inhibitory effect on cyclooxygenase (COX). However, COX-independent mechanisms involving kinase inhibition have been proposed to explain certain therapeutic effects of NSAIDs. H...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.04.012
更新日期：2010-07-25 00:00:00
abstract：:We have investigated the effect of inhaled HOE 140, a novel bradykinin B2 receptor antagonist, against bradykinin- and vagal stimulation-induced airway microvascular leakage and bronchoconstriction in anesthetized guinea-pigs. Lung resistance was measured for 6 min after challenge, followed by measurement of extravasa...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)90393-x
更新日期：1994-01-14 00:00:00
abstract：:Activating mutations in FMS-like tyrosine kinase 3 (FLT3) occur in 25% of acute lymphoid and 30% of acute myeloid leukaemia cases. Therefore, FLT3 is a potential therapeutic target for small molecule kinase inhibitors. In this study, protein-ligand interactions between FLT3 and kinase inhibitors (CEP701, PKC412, sunit...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2016.02.048
更新日期：2016-04-05 00:00:00
abstract：:Intravenous (i.v.) administration of cytidine-5'-diphosphate choline (CDP-choline) (100, 250 and 500 mg/kg) increased blood pressure in normal rats and reversed hypotension in haemorrhagic shock. Choline (54 mg/kg; i.v.), at the dose equimolar to 250 mg/kg CDP-choline decreased blood pressure of rats in both condition...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(03)01602-9
更新日期：2003-05-09 00:00:00
abstract：:Aspirin (acetylsalicylic acid), the oldest synthetic drug, was originally used as an anti-inflammatory medication. Being an irreversible inhibitor of COX (prostaglandin-endoperoxide synthase) enzymes that produce precursors for prostaglandins and thromboxanes, it has gradually found several other applications. Sometim...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2019.172762
更新日期：2020-01-05 00:00:00
abstract：:Using microscopic fluorometry and fura-2-loaded cultured bovine aortic endothelial cells, we determined the effects of captopril, an angiotensin converting enzyme (ACE) inhibitor, on bradykinin-induced Ca2+ transients in endothelial cells. In the presence of extracellular Ca2+, 10(-9) M bradykinin induced an early ris...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(93)90018-5
更新日期：1993-01-15 00:00:00
abstract：:The effect of KC 2450 (racemic 3,5-cis-3-methylamino-2,3,4,5-tetrahydro-1-benzoxepine-5-ol hydrochloride) on lower esophageal sphincter pressure in pentobarbital-anesthetized dogs was determined and compared to the effect of metoclopramide. The ED20 value (i.e. the dose that increased lower esophageal sphincter pressu...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90111-7
更新日期：1987-10-13 00:00:00
abstract：:Oral pretreatment with E3330, a novel quinone derivative, attenuated liver injury induced with tumor necrosis factor-alpha in galactosamine-sensitized mice. Tumor necrosis factor-alpha is known to induce inflammatory mediators such as leukotrienes and prostanoids. An in vitro study showed that E3330 inhibited the gene...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90286-d
更新日期：1992-12-08 00:00:00
abstract：:Pentobarbital anesthetized rats subjected to Noble-Collip drum trauma developed a shock state characterized by marked hypotension, increases in plasma cathepsin D (9.6-fold), free amino-nitrogen (4.0-fold), and myocardial depressant factor (5.2-fold) activities, and a survival time of 1.90 +/- 0.23 h. Following the in...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90487-q
更新日期：1990-06-21 00:00:00
abstract：:Rolipram was characterized for its emetic, behavioral, cardiovascular and pulmonary activities in dogs, to assess its systemic pharmacology and potential bronchodilatory selectivity. At doses > or = 0.1 mg/kg i.v., rolipram induced emesis, anxiety, and stepping behaviors in conscious dogs, and increased heart rate and...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00457-2
更新日期：1995-11-24 00:00:00
abstract：:Endogenous Nitric Oxide (NO) plays a key role in the physiological regulation of airway functions. In response to various stimuli activated inflammatory cells (e.g., eosinophils and neutrophils) generate oxidants ("oxidative stress") which in conjunction with exaggerated enzymatic release of NO and augmented NO metabo...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2005.12.057
更新日期：2006-03-08 00:00:00
abstract：:Multiple high-dose administrations of the dopamine-releasing agent, methamphetamine, rapidly and persistently decrease vesicular dopamine uptake in purified vesicles prepared from striata of treated rats. Because important differences in the neurotoxic effects of stimulants have been documented in rats and mice, the p...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(03)01911-3
更新日期：2003-07-11 00:00:00
