Abstract:
:The effects of 10 mM caffeine (CAF) on intramembrane charge movements (ICM) were studied in isolated guinea-pig ventricular heart cells with the whole-cell patch-clamp technique. In the presence of CAF, the properties (voltage dependence, maximum Q(ON) [Q(max)], availability with voltage) of Q(ON) charge activated from -110 mV were barely affected. Following a 100 ms prepulse to -50 mV to decrease the participation of charges originating from Na channels, the voltage dependence of Q(ON) was shifted by 5 mV (negative component) and by 10 mV (positive component) towards negative potentials, and Q(max) was depressed by 16.5%. CAF drastically reduced in a time- and voltage-dependent manner Q(OFF) on repolarization to -50 mV, the effects being greater at positive potentials. CAF-induced Q(OFF) immobilization could be almost entirely removed by repolarization to voltages as negative as -170 mV. In these conditions, the voltage-dependence of Q(OFF) (repolarization to +30 to -170 mV) was shifted by 17 mV (negative component) and 30 mV (positive component) towards negative potentials, suggesting an interconversion into charge 2. Most of CAF effects were suppressed when the sarcoplasmic reticulum (SR) was not functional or when the cells were loaded with BAPTA-AM. We conclude that CAF effects on ICM are likely due to Ca(2+) ions released from the SR, and which accumulate in the subsarcolemmal fuzzy spaces in the vicinity of the Ca channels. Because CAF effects were more pronounced on Q(OFF) than on Q(ON) the channels have likely to open before Ca(2+) ions could affect their gating properties. It is speculated that such an effect on gating charges might contribute to the Ca-induced inactivation of the Ca current.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Leroy J,Lignon JM,Gannier F,Argibay JA,Malécot COdoi
10.1038/sj.bjp.0704520subject
Has Abstractpub_date
2002-02-01 00:00:00pages
721-34issue
3eissn
0007-1188issn
1476-5381journal_volume
135pub_type
杂志文章abstract::1. Using gene chip technology, we first identified that PGF(2alpha) (FP agonist) and Butaprost (EP(2) agonist) induced about a five-fold upregulation of Nur77 mRNA expression in hFP-HEK 293/EBNA and hEP(2)-HEK293/EBNA cells. Northern Blot analysis revealed that PGF(2alpha)- and Butaprost-induced upregulation of Nur77 ...
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
abstract:BACKGROUND AND PURPOSE:Memantine and ketamine are clinically used, open-channel blockers of NMDA receptors exhibiting remarkable pharmacodynamic similarities despite strikingly different clinical profiles. Although NMDA channel gating constitutes an important difference between memantine and ketamine, it is unclear how...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13007
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abstract:BACKGROUND AND PURPOSE:Although CB(1) receptor activation evokes neuroprotection in response to cannabinoids, some cannabinoids have been reported to be peroxisome proliferator activated receptor (PPAR) ligands, offering an alternative protective mechanism. We have, therefore, investigated the ability of a range of can...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707478
更新日期:2007-11-01 00:00:00
abstract::1. In the presence of atropine, mepyramine and ranitidine, electric field stimulation of the guinea-pig isolated ileum longitudinal muscle-myenteric plexus preparation resulted in a two component non-adrenergic non-cholinergic contraction. The initial contraction had a duration of approximately 1 s whereas the second ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb09036.x
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abstract::1. We aimed to determine whether there are any changes in responsiveness of the mesenteric arterial beds to phenylephrine (Phe) and KCl in exercise-trained rats, and whether vascular endothelium and/or vascular smooth muscle play a role in these changes. 2. Adult male rats were subjected to a swimming schedule every d...
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doi:10.1038/sj.bjp.0702697
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abstract:BACKGROUND AND PURPOSE:Metformin, a small molecule, antihyperglycaemic agent, is a well-known activator of AMP-activated protein kinase (AMPK) and protects against cardiac fibrosis. However, the underlying mechanisms remain elusive. TGFβ1 is a key cytokine mediating cardiac fibrosis. Here, we investigated the effects o...
journal_title:British journal of pharmacology
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doi:10.1111/bph.13753
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abstract:BACKGROUND AND PURPOSE:Anxiety disorder is a common mental health disorder. However, there are few safe and fast-acting anxiolytic drugs available that can treat anxiety disorder. We previously demonstrated that the interaction of neuronal NOS (nNOS) with its carboxy-terminal PDZ ligand (CAPON) is involved in regulatin...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.15084
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abstract::1. The concentrations of 5-hydroxytryptamine (5-HT), 5-hydroxyindolacetic acid (5-HIAA) and noradrenaline (NA) in homogenized rat brains were determined after intraperitoneal injection of 1,2,3,4-tetrahydro-2-naphthylamine (THN).2. THN caused a decrease in the concentration of brain 5-HIAA without altering its 5-HT co...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1971.tb07109.x
更新日期:1971-06-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1980.tb07937.x
更新日期:1980-10-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703552
更新日期:2000-09-01 00:00:00
abstract::The interaction of ketamine with the 5-HT3 receptor of rabbit nodose ganglion neurones is described. Ketamine (3-30 microM) enhanced 5-HT3 receptor-mediated currents recorded under voltage-clamp conditions. This action did not appear to be related to the known effect of ketamine of inhibiting 5-HT uptake. ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb09837.x
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abstract:BACKGROUND AND PURPOSE:There is growing interest in the physiological functions of flavonoids, especially in their effects on cognitive function and on neurodegenerative diseases. The aim of the current investigation was to evaluate the role of the flavonoid baicalein in long-term potentiation (LTP) in the hippocampal ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.01143.x
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abstract:BACKGROUND AND PURPOSE:3,4-Methylenedioxymethamphetamine (MDMA or 'Ecstasy') is a worldwide major drug of abuse known to elicit neurotoxic effects. The mechanisms underlying the neurotoxic effects of MDMA are not clear at present, but the metabolism of dopamine and 5-HT by monoamine oxidase (MAO), as well as the hepati...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:2012-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Memantine and marijuana smoking have been found to inhibit tremor in parkinsonian patients, although the observed effects were relatively weak. The tremorolytic effects of combinations of memantine and cannabinoids have not been studied. Here, we have evaluated the anti-tremor activity of memanti...
journal_title:British journal of pharmacology
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb10069.x
更新日期:1984-02-01 00:00:00
abstract::The vasorelaxant activity of eicosapentaenoic acid (EPA, 20:5n-3), the omega-3 polyunsaturated fatty acid, was investigated in isolated Wistar Kyoto (WKY) rat aortae by measuring isometric tension. Eicosapentaenoic acid (1 - 100 microM) relaxed rat aortae contracted with high K(+) (80 mM) or noradrenaline (NA, 1 micro...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703754
更新日期:2000-12-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb08124.x
更新日期:1972-08-01 00:00:00
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journal_title:British journal of pharmacology
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更新日期:2017-12-01 00:00:00
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journal_title:British journal of pharmacology
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更新日期:2017-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb08114.x
更新日期:1972-08-01 00:00:00
abstract::Knowledge of the cardiac safety of emerging new drugs is an important aspect of assuring the expeditious advancement of the best candidates targeted at unmet medical needs while also assuring the safety of clinical trial subjects or patients. Present methodologies for assessing drug-induced torsades de pointes (TdP) a...
journal_title:British journal of pharmacology
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doi:10.1038/bjp.2008.279
更新日期:2008-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The endocannabinoid system and the cannabinoid CB(1) receptor have been identified in human sperm, and it is well known that endocannabinoids have pronounced adverse effects on male and female reproduction. In order to elucidate further the pathophysiological role of the endocannabinoid system in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00570.x
更新日期:2010-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:We previously demonstrated that paracetamol has to be metabolised in the brain by fatty acid amide hydrolase enzyme into AM404 (N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamide) to activate CB1 receptors and TRPV1 channels, which mediate its analgesic effect. However, the brain mechanisms sup...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14934
更新日期:2020-04-01 00:00:00
abstract::In this study we have determined the different signalling pathways involved in adenosine A(1)-receptor (A(1)-receptor)-dependent inhibition of contractility in rat isolated atria. N-cyclopentyladenosine (CPA) stimulation of A(1)-receptor exerts: negative inotropic response, inositol phosphates accumulation, stimulatio...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704487
更新日期:2002-01-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13441
更新日期:2016-04-01 00:00:00
abstract::Electrical field stimulation (EFS)-induced non-adrenergic non-cholinergic (NANC) relaxation responses in the rabbit vaginal wall were investigated. These NANC responses were partially inhibited with the nitric oxide synthase (NOS) inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME; 500 microM), N(G)-nitro-L-arginin...
journal_title:British journal of pharmacology
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:2011-07-01 00:00:00
abstract::The effect of propranolol, a beta-adrenoceptor blocking agent, has been investigated on gastric acid secretion in pylorus and cardiac-ligated rats. Compared to the control group, propranolol significantly diminished the gastric acid secretion, and inhibited the formation of gastric ulceration. ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb06860.x
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abstract:BACKGROUND AND PURPOSE:Idiopathic pulmonary fibrosis (IPF) is a progressive fibro-proliferative disorder refractory to current therapy commonly complicated by the development of pulmonary hypertension (PH); the associated morbidity and mortality are substantial. Natriuretic peptides possess vasodilator and anti-fibroti...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12694
更新日期:2014-07-01 00:00:00
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journal_title:British journal of pharmacology
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