Abstract:
:1. By use of a number of analogues of adenine nucleotides, the structure-activity relationships of the human platelet receptor for adenosine 5'-diphosphate (ADP) mediating increases in intracellular calcium were investigated, and compared with the known structure-activity relationships for induction by ADP of platelet aggregation. 2. ADP, 2-methylthioadenosine 5'-diphosphate (2-methylthio-ADP), adenosine 5'-O-(1-thiodiphosphate) (ADP-alpha-S) and adenosine 5'-O-(2-thiodiphosphate) (ADP-beta-S) each induced increases in intracellular calcium in a manner similar to their reported ability to induce human platelet aggregation. The effects of these agonists were antagonized by ATP, with a pA2 value in each case consistent with the inhibition by ATP of ADP-induced aggregation. In the case of ADP, the inhibition by ATP of increases in intracellular calcium was shown to be competitive by Schild analysis. 3. Of the analogues tested as inhibitors of the effect of ADP on intracellular calcium, 2-chloroadenosine 5'-triphosphate (2-chloro-ATP), adenosine 5'-O-(1-thiotriphosphate) (ATP-alpha-S), P1, P5-diadenosine pentaphosphate (Ap5A) and adenylyl 5'-(beta,gamma-methylene)diphosphonate (AMPPCP) were apparently competitive antagonists, although only one concentration of each antagonist was used. There was a good correlation between the pA2 values found here for these antagonists including ATP, and their pA2 values reported for inhibition of ADP-induced aggregation. Adenosine 5'-(alpha, beta-methylene)triphosphate (AMPCPP) and uridine 5'-triphosphate (UTP) (100 microM) were only very weak inhibitors of the effect of ADP on intracellular calcium, and this is consistent with their weak actions as inhibitors of aggregation. 2-Methylthioadenosine 5'-triphosphate (2-methylthio-ATP) (50 microM) non-competitively inhibited the effect of ADP on intracellular calcium, in a very similar way to its inhibition of ADP-induced aggregation.4. The good correspondence found for these analogues between their effect on intracellular calcium and on aggregation confirms that there is a causal relationship between these actions of ADP, and that they are mediated by the same receptor on platelets. These findings cast further doubt on the use of the affinity reagent 5'-fluorosulphonylbenzoyladenosine (FSBA) as an antagonist and label for the ADP receptor, as this compound has been reported to inhibit aggregation but not ADP-induced increases in intracellular calcium.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Hall DA,Hourani SMdoi
10.1111/j.1476-5381.1993.tb12869.xsubject
Has Abstractpub_date
1993-03-01 00:00:00pages
728-33issue
3eissn
0007-1188issn
1476-5381journal_volume
108pub_type
杂志文章abstract::1. The subtypes of endothelin receptors that mediate the effects of endothelin-1 (ET-1) on mean arterial pressure (MAP), heart rate (HR), mean circulatory filling pressure (MCFP), arterial resistance (RA), cardiac output (CO) and venous resistance (RV) were characterized in 9 groups of pentobarbitone-anaesthetized rat...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701474
更新日期:1997-11-01 00:00:00
abstract::1. alpha 1-Adrenoceptor subtypes in rabbit thoracic aorta have been examined in binding and functional experiments. 2. [3H]-prazosin bound to two distinct populations of alpha 1-adrenoceptors (pKD,high = 9.94, Rhigh = 79.2 fmol mg-1 protein; pKD,low = 8.59, Rlow = 215 fmol mg-1 protein). Pretreatment with chloroethylc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13507.x
更新日期:1993-04-01 00:00:00
abstract::1 In unanaesthetized cats, the administration of 6-hydroxydopamine (6-OHDA), 750 mug, via the lateral cerebral ventricle produced a pronounced fall in rectal temperature but only a slight fall when repeated 7 days later. At this time hypothalamic noradrenaline concentration had diminished to 4% of control.2 In these a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb09648.x
更新日期:1974-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Sildenafil is a selective inhibitor of cGMP-specific phosphodiesterase. Sildenafil, acting via NO-dependent mechanisms, prevents indomethacin-induced gastropathy. Activation of ATP-sensitive potassium channels (K(ATP)) is involved in gastric defence. Our objective was to evaluate the role of the ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707605
更新日期:2008-02-01 00:00:00
abstract::A hallmark of heart failure is mitochondrial dysfunction leading to a bioenergetics imbalance in the myocardium. Consequently, there is much interest in targeting mitochondrial abnormalities to attenuate the pathogenesis of heart failure. This review discusses (i) how electron microscopy (EM) techniques have been fund...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.14499
更新日期:2019-11-01 00:00:00
abstract::1. Effects of oestradiol on the electrical and mechanical properties of the rabbit basilar artery were investigated by use of microelectrode, patch-clamp and isometric tension recording methods. 2. Oestradiol (10 nM-100 microM) relaxed arterial tissue pre-contracted by excess [K]o solution (30 mM) in a concentration-d...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15198.x
更新日期:1996-01-01 00:00:00
abstract::1. We studied the effect of intracellular angiotensin II (Ang II) and related peptides on rat aortic contraction, whether this effect is pharmacologically distinguishable from that induced by extracellular stimulation, and determined the Ca2+ source involved. 2. Compounds were delivered into the cytoplasm of de-endoth...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702421
更新日期:1999-03-01 00:00:00
abstract::1 Subcutaneous administration of glucagon (1 and 0.5 mg/kg) 30 min before the injection of carrageenin or dextran into the rat's paw reduced oedema and the local exudation of Evans blue previously given intravenously. 2 The effect persisted after removal of the adrenal medulla but not after adrenalectomy. 3 When gluca...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb07611.x
更新日期:1975-09-01 00:00:00
abstract::1 The effect of methylene, thio, and imido substituted analogues of adenosine 5'-triphosphate (ATP) on surfactant phospholipid secretion and calcium mobilization in rat isolated alveolar Type II cells was studied. 2 ATP was the most potent secretagogue of adenine nucleotides studied. The rank order of agonist potency ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb11282.x
更新日期:1987-08-01 00:00:00
abstract::1. Carrageenin or 5-hydroxytryptamine-induced oedema of the mouse hind paw was antagonized by catecholamines acting on both alpha- and beta-adrenoceptors.2. Increased permeability of the mouse peritoneum induced by the local injection of acetic acid or pro-inflammatory mediators was antagonized by catecholamines actin...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb08086.x
更新日期:1972-06-01 00:00:00
abstract::1. The regulation of adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels by cholinoceptors has been studied in cultured bovine adrenal medullary cells. 2. Acetylcholine (100 microM), nicotine (10 microM) and dimethylphenylpiperazinium (20 microM) each increased cellular cyclic AMP levels 2 to 4 fold over 5 min in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14341.x
更新日期:1992-06-01 00:00:00
abstract::Myeloperoxidase (MPO), a member of the haem peroxidase-cyclooxygenase superfamily, is abundantly expressed in neutrophils and to a lesser extent in monocytes and certain type of macrophages. MPO participates in innate immune defence mechanism through formation of microbicidal reactive oxidants and diffusible radical s...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0707358
更新日期:2007-11-01 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...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703451
更新日期:2000-08-01 00:00:00
abstract::I.c.v. self-administration of MDMA (0.01-2 micro g per infusion), alone and in combination with CP 55,940 (0.4 micro g infusion(-1)), was studied on an operant responding procedure. On the basis of individual preference for one of two levers, developed during training, rats were allowed to self-administer vehicle from...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704825
更新日期:2002-08-01 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.tb09278.x
更新日期:1982-09-01 00:00:00
abstract::1 Release of [3H]-noradrenaline and 3H-purine by ouabain (10(-4)M) or high KCl (50 mM) was investigated in the superfused rabbit pulmonary arterial segment preincubated with [3H]-noradrenaline or [3H]-adenosine. 2 Ouabain elicited a delayed large contraction and a parallel [3H]-noradrenaline efflux. These were substan...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09340.x
更新日期:1982-12-01 00:00:00
abstract::1. The possible mechanisms of action of the inhibitory effect of gomisin C on the respiratory burst of rat neutrophils in vitro was investigated. 2. The peptide formyl-Met-Leu-Phe (FMLP) induced superoxide anion (O2-) formation and O2 consumption, which was inhibited by gomisin C in a concentration-dependent manner (I...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17084.x
更新日期:1994-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Inhibition of the T- and B-cell interaction through the CD40/CD40 ligand (L) axis is a favourable approach for inflammatory disease treatment. Clinical studies of anti-CD40L molecules in autoimmune diseases have met challenges because of thromboembolic events and adverse haemostasis. VIB4920 (for...
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1972.tb07297.x
更新日期:1972-03-01 00:00:00
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1987.tb08983.x
更新日期:1987-05-01 00:00:00
abstract::1. Intraplantar administration of the nitric oxide (NO) donor, sodium nitroprusside (SNP), induces hyperaemia in the rat paw skin, which is in part due to release of calcitonin gene-related peptide (CGRP) from afferent nerve fibres. The present study examined whether prostaglandins or other inflammatory mediators part...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb15081.x
更新日期:1995-11-01 00:00:00
abstract::1. We previously reported that substance P and insulin-like growth factor-1 (IGF-1) synergistically stimulate corneal epithelial wound healing in vitro and in vivo. We wished to identify which portion of the amino acid sequence of substance P might be responsible for this synergism. 2. Corneal epithelial migration was...
journal_title:British journal of pharmacology
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doi:10.1038/sj.bjp.0702550
更新日期:1999-05-01 00:00:00
abstract::1 The responses of the smooth muscle of the capsule and blood vessels of the isolated, blood-perfused spleen of the dog to angiotensin, oxytocin and vasopressin have been investigated and compared to the actions of the catecholamines, adrenaline and noradrenaline.2 Increasing doses of each of the three polypeptides ca...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb06930.x
更新日期:1975-06-01 00:00:00
abstract::1. The regulatory mechanism for the hypertrophy of skeletal muscles induced by clenbuterol is unclear. The purpose of the present study was to determine the extent to which transforming growth factor betas (TGFbetas), fibroblast growth factors (FGFs), hepatocyte growth factor (HGF), and platelet-derived growth factors...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706625
更新日期:2006-02-01 00:00:00
abstract::1. Repeated allergen challenge has been shown to increase the role of Rho-kinase in airway smooth muscle (ASM) contraction. We considered the possibility that active allergic sensitization by itself, that is, without subsequent allergen exposure, could be sufficient to enhance Rho-kinase-mediated ASM contraction. 2. G...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705903
更新日期:2004-10-01 00:00:00
abstract::1 The concept that nitric oxide (NO) release can be beneficial in inflammatory conditions has raised more attention in the recent years, particularly with the development of nitric oxide-releasing anti-inflammatory drugs. There is considerable evidence that NO is capable of enhancing the anti-inflammatory benefits of ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:2004-11-01 00:00:00
abstract::If one drug, B, antagonizes another, A, by producing the opposite physiological effect, the antagonist concentration-effect curves should be affected by the recording system, which limits the range of agonist responses. With pieces of isolated guinea-pig ileum taken from adjacent parts of the same animal, one recorded...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704169
更新日期:2001-08-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb10254.x
更新日期:1986-07-01 00:00:00
abstract::1.--The small protein Bv8, isolated from the amphibian skin, belongs to a novel family of secreted proteins linked to several biological effects. We describe the expression of Bv8/prokineticins and their receptors in mouse macrophages, and characterize their proinflammatory activities. 2.--The rodent analogue of Bv8, ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706467
更新日期:2006-01-01 00:00:00
abstract::Since its discovery over 50 years ago, cAMP has been the archetypal second messenger introducing students to the concept of cell signalling at the simplest level. As explored in this review, however, there are many more facets to cAMP signalling than the path from Gs-coupled receptor to adenylyl cyclase (AC) to cAMP t...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2011.01719.x
更新日期:2012-05-01 00:00:00