Abstract：
:Inhibition of myocardial Ca2+ channels was investigated for three dihydropyridines with different structural features: Ro 18-3981, darodipine (PY 108-068) and nifedipine. Ro 18-3981 contains a sulphamoyl acetyl side-chain. In voltage-clamps experiments with isolated cardiac myocytes of guinea-pig, Ro 18-3981 caused a concentration-dependent inhibition of the Ca2+ current, which was influenced by the membrane holding potential. A markedly greater inhibition by Ro 18-3981 was observed when myocytes were depolarized (to +10 mV) from a holding potential (Vh) of -20 mV (IC50 = 2.3 nm) than at -50 mV (IC50 = 100 nM). The three dihydropyridines caused a concentration-dependent reduction in contractile force of isolated, electrically-stimulated left atria of the guinea-pig. Elevation of the extracellular K+ concentration from 5.9 to 24 mM resulted in a significant reduction in negative inotropic IC50 values for Ro 18-3981 (137 fold), darodipine (8 fold) and nifedipine (20 fold). The affinity of these drugs for the high-affinity (+)-[3H]-PN 200-110 binding site was determined in guinea-pig cardiac membranes. The KD value of Ro 18-3981 (1.0 nM) was similar to the IC50 value for blockade of ICa at a Vh of -20 mV (2.3 nM), i.e. at a level of near-maximal depolarization. Thus, structurally-different dihydropyridines exert potential-dependent inhibition of myocardial Ca2+ channel activity consistent with the modulated receptor hypothesis. These results demonstrate that blockade of myocardial excitation-contraction coupling by Ca2+ entry blockers is also potential-dependent.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Holck M,Osterrieder Wdoi
10.1111/j.1476-5381.1987.tb08983.xsubject
Has Abstractpub_date
1987-05-01 00:00:00pages
61-7issue
1eissn
0007-1188issn
1476-5381journal_volume
91pub_type
杂志文章abstract：:1. Alterations of 5-hydroxytryptaminergic mechanisms are thought to play a special role in the pathogenesis of depression and antidepressant treatments are assumed to restore these changes. 2. We have used one of the most reliable models of depression, the olfactory bulbectomized rat to study the long term consequence...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701530
更新日期：1997-12-01 00:00:00
abstract：BACKGROUND:Anandamide (AEA) activates both cannabinoid CB(1) and TRPV1 receptors, which are expressed on cultured dorsal root ganglion neurones. Increased levels of nerve growth factor (NGF) are associated with chronic pain states. EXPERIMENTAL APPROACH:The aim of this study was to compare of the effects of AEA on CB(...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707411
更新日期：2007-10-01 00:00:00
abstract：:1. Alterations in the levels of intracellular calcium ([Ca2+]i) and D-myo-inositol-1,4,5-trisphosphate (InsP3) were measured in the murine neuroblastoma cell line clone, N1E-115, by use of the calcium-sensitive dye, fura-2 and a radioreceptor assay, respectively. 2. Exposure of the cells to ATP (100 microM) elicited r...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb13410.x
更新日期：1992-12-01 00:00:00
abstract：BACKGROUND AND PURPOSE:alpha5IA (3-(5-methylisoxazol-3-yl)-6-[(1-methyl-1,2,3-triazol-4-yl)methyloxy]-1,2,4-triazolo[3,4-a]phthalazine) is a triazolophthalazine with subnanomolar affinity for alpha1-, alpha2-, alpha3- and alpha5-containing GABA(A) receptors. Here we have evaluated the relationship between plasma alpha5...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00216.x
更新日期：2009-07-01 00:00:00
abstract：:Amyotrophic lateral sclerosis (ALS) is the most common motor neuron neurodegenerative disease. Although it has been classically considered as a disease limited to the motor system, there is increasing evidence for the involvement of other neural and non-neuronal systems. In this review, we will discuss currently exist...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.15202
更新日期：2020-07-16 00:00:00
abstract：BACKGROUND AND PURPOSE:Some neurosteroids, notably 3alpha-hydroxysteroids, positively modulate GABA(A) receptors, but sulphated steroids negatively modulate these receptors. Recently, other lipophilic amphiphiles have been suggested to positively modulate GABA receptors. We examined whether there was similarity among t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.00679.x
更新日期：2010-05-01 00:00:00
abstract：:1. The effect of the nitro-derivative of aspirin, NCX4016, was assessed on ischaemic ventricular arrhythmias and myocardial infarct size in anaesthetized pigs in comparison to native aspirin. 2. Pigs were given aspirin (10 mg kg(-1); n=6), low dose NCX4016 (18.4 mg kg(-1); n=6) or high dose NCX4016 (60 mg kg(-1); n=7)...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704646
更新日期：2002-04-01 00:00:00
abstract：:1. Endothelial cell damage in glomeruli and kidney arterioles appears to play a pivotal role in glomerular inflammatory diseases. Glomerular endothelial cells, a specialized microvascular cell type involved in the regulation of glomerular ultrafiltration, die by apoptosis in response to tumour necrosis factor-alpha (T...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702726
更新日期：1999-08-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Small conductance calcium-activated potassium (KCa 2.x) channels have a widely accepted canonical function in regulating cellular excitability. In this study, we address a potential non-canonical function of KCa 2.x channels in breast cancer cell survival, using in vitro models. EXPERIMENTAL APP...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13357
更新日期：2016-01-01 00:00:00
abstract：:Immersion of the hind paws of anesthetized rats in hot water for 5 min induced massive plasma protein leakage as indicated by extravasation of Evans blue dye in the skin. The threshold temperature which caused noticeable plasma extravasation was 45 degrees C, a maximal response was obtained between 55 degrees C and 60...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1984.tb16461.x
更新日期：1984-05-01 00:00:00
abstract：:1. Female mice of the Hough/Porton and Tuck/TO strains were found to be more sensitive than male mice to the diuretic effects of oral and intravenous doses of ethacrynic acid. 2. The sensitivity of Hough/Porton male mice to ethacrynic acid was increased after pretreatment with stilboestrol and the sensitivity of femal...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1977.tb07536.x
更新日期：1977-08-01 00:00:00
abstract：BACKGROUND:Dimebolin (latrepirdine), a compound with multiple potential drug targets, is being evaluated in clinical trials for the treatment of Alzheimer's disease (AD) and preliminary results suggest it can slow the disease process. There is also evidence that dimebolin directly improves aspects of cognition. Here we...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01432.x
更新日期：2011-10-01 00:00:00
abstract：:1. The effects of the muscarinic agonist carbachol on phosphoinositide metabolism and its relationship to alteration of intracellular calcium were examined in SK-N-SH human neuroblastoma cells. Muscarinic receptors on these cells are coupled to phospholipase C and the myo [2-3H]-inositol phosphates resulting from rece...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12681.x
更新日期：1989-12-01 00:00:00
abstract：:1. The type of endothelin (ET) receptor located on the myenteric neurones of guinea-pig ileum was determined by receptor autoradiography and function of the receptor was examined by release experiments of acetylcholine (ACh) from the longitudinal muscle myenteric plexus (LM-MP) preparations. 2. Specific [125I]-ET-1 bi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15520.x
更新日期：1996-07-01 00:00:00
abstract：:1. Prostaglandins and the vasodilator neuropeptide, calcitonin-gene related peptide (CGRP), have both been implicated in the pathogenesis of migraine headache. We have used primary cultures of adult rat trigeminal neurones to examine the effects of prostanoids on CGRP release in vitro. 2. CGRP release was stimulated b...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704357
更新日期：2001-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Pancreatic cancer is characterized by alterations in several key signalling proteins, including increased expression and activity of the Src tyrosine kinase and focal adhesion kinase (FAK), which have been linked to its chemoresistance. Sustained Src inhibition reactivates survival pathways regul...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12855
更新日期：2015-01-01 00:00:00
abstract：:In the clinic, low efficacy positive GABAA modulators might be preferred to high efficacy positive modulators insofar as low efficacy modulators might have comparatively less abuse and dependence liability. Drug discrimination was used to examine the behavioral effects of L-838,417 and bretazenil, two low efficacy pos...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706550
更新日期：2006-02-01 00:00:00
abstract：BACKGROUND AND PURPOSE:An alteration in the communication between the innate and adaptive immune cells is a hallmark of ulcerative colitis (UC). Semaphorin-3E (SEMA3E), a secreted guidance protein, regulates various immune responses. EXPERIMENTAL APPROACH:We investigated the expression of SEMA3E in colonic biopsies of...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14614
更新日期：2019-05-01 00:00:00
abstract：:Two prostaglandin endoperoxide analogues, EP 035 and EP 157, behave as specific thromboxane receptor antagonists on isolated smooth muscle preparations such as rabbit aorta, dog saphenous vein and guinea-pig trachea. However, in human platelet-rich plasma (PRP) they produce an unsurmountable block of aggregation induc...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb10196.x
更新日期：1986-03-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Erectile dysfunction is highly prevalent in diabetic patients and PDE V inhibitors are effective and safe for the treatment of erectile dysfunction in men with diabetes. Therefore, in this study we investigated whether a pharmacokinetic interaction occurs between DA-8159 and metformin, as both dr...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707680
更新日期：2008-04-01 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：BACKGROUND AND PURPOSE:Previous findings suggest that the growth and differentiation factor midkine (Mdk) is a negative regulator of osteoblast activity and bone formation, thereby raising the possibility that a specific Mdk antagonist might improve bone formation during fracture healing. EXPERIMENTAL APPROACH:In the ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13503
更新日期：2016-07-01 00:00:00
abstract：:1. The biotransformation of prostaglandin E(1) (PGE(1)) was studied in the isolated, perfused dog kidneys.2. An average 43% of PGE(1) was converted into the less polar metabolite I by a single passage through the kidney. As the re-circulation of the perfusate continued, PGE(1) was converted not only into metabolite I ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1970.tb09924.x
更新日期：1970-10-01 00:00:00
abstract：:1 Physiologically, perisinusoidal hepatic stellate cells (HSC) are quiescent and store retinoids. During liver injury and in cell culture, HSC transform into proliferating myofibroblast-like cells that express alpha-smooth muscle actin (alpha-sma) and produce excessive amounts of extracellular matrix. During transform...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705303
更新日期：2003-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Resurgence in the use of chloroquine as a potential treatment for COVID-19 has seen recent cases of fatal toxicity due to unintentional overdoses. Protocols for the management of poisoning recommend diazepam, although there are uncertainties in its pharmacology and efficacy in this context. The a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.15101
更新日期：2020-11-01 00:00:00
abstract：:1. The effects of four specific inhibitors of 5-hydroxytryptamine (K-HT) uptake on morphine-, methadone- or pethidine-induced antinociception was studied in rats. Antinociception was assessed by means of hot plate (55 degrees C) reaction times. The effect of the compounds on the uptake of [3H]-5-HT into rat whole brai...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1979.tb07881.x
更新日期：1979-04-01 00:00:00
abstract：:A method is described for the determination of halothane-induced sleeping time in the rat. 2 The sleeping time exhibited a diurnal variation which was due, at least in part, to a change in the sensitivity of the central nervous system (CNS) to the anaesthetic. 3 Tolerance to halothane did not develop in rats repeatedl...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1976.tb07689.x
更新日期：1976-09-01 00:00:00
abstract：:1. The purpose of this study was to determine if corpus cavernosum smooth muscle expresses functional postsynaptic alpha2-adrenoceptors (AR). 2. The alpha2-adrenoceptor agonist UK 14,304 elicited concentration-dependent contractions in rabbit corpus cavernosum smooth muscle (CCSM). The half-maximal response occurred a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701739
更新日期：1998-03-01 00:00:00
abstract：BACKGROUND AND PURPOSE:A functional link between seizure-induced P-glycoprotein overexpression at the blood-brain barrier and therapeutic failure has been suggested by several studies using rodent epilepsy models and human epileptic tissue. Recently, we reported that interference with the mechanisms that up-regulate P-...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.00765.x
更新日期：2010-07-01 00:00:00
abstract：:The effect of a substance P antagonist, [D-Pro2, D-Trp7,9]-substance P (SPA), on gastric emptying and gastrointestinal transit in the rat was studied in order to elucidate a possible physiological role of endogenous substance P and other tachykinins in gastrointestinal motility. SPA was given by intraperitoneal inject...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb11144.x
更新日期：1986-11-01 00:00:00
