Abstract:
:Palmitaldehyde acetal phosphatidic acid ( PGAP ) caused dose-dependent aggregation of human platelets resuspended in modified Tyrode medium, with a threshold concentration of 0.5-1 microM and an EC50 of 4 microM. Concentrations of PGAP which elicited biphasic irreversible aggregation concomitantly induced formation of 1.02 +/- 0.029 nmol (mean +/- s.e. mean) of malondialdehyde (MDA) per 10(9) platelets and caused release of 58 +/- 2.8% of platelet [14C]-5-hydroxytryptamine ([14C]-5-HT) from prelabelled platelets; no MDA formation or [14C]-5-HT release occurred at lower doses of PGAP which elicited only monophasic reversible aggregation. Adenosine 5'-pyrophosphate (ADP)-induced platelet activation resulted in formation of 0.344 +/- 0.004 nmol of MDA per 10(9) platelets in association with irreversible aggregation and 49.1 +/- 1% release of [14C]-5-HT. Mepacrine, a phospholipase A2 inhibitor, at 2.5 microM reduced PGAP -induced MDA formation and [14C]-5-HT release by the resuspended platelets without affecting irreversible aggregation; higher concentrations of mepacrine abolished all three responses. Chlorpromazine, a calmodulin antagonist, similarly inhibited PGAP -induced MDA formation and irreversible aggregation, and at 100 microM abolished monophasic aggregation. The cyclo-oxygenase inhibitor indomethacin caused a concentration-dependent reduction of PGAP -induced MDA formation by resuspended human platelets without significantly inhibiting [14C]-5-HT release or irreversible aggregation; concentrations (greater than or equal to 1.75 microM) which inhibited MDA formation by more than 94% abolished [14C]-5-HT release, and converted second phase irreversible aggregation to an extensive reversible response. 2-Methylthioadenosine 5'-phosphate (2 methylthio-AMP), an ADP antagonist, inhibited PGAP -induced MDA formation, [14C]-5-HT release and second phase aggregation in the human platelet suspensions in a parallel, concentration-dependent manner; at 9.4 microM 2-methylthio-AMP, both MDA formation and [14C]-5-HT release were abolished and monophasic, reversible aggregation remained. Albumin was required for aggregation of washed human platelets to PGAP . Irreversible PGAP -induced aggregation of washed [14C]-arachidonate-labelled platelets was accompanied by a low net loss of 14C from platelet phospholipids, an equivalent increase in 14C in free fatty acids, and the appearance of 14C in thromboxane (Tx)B2; mepacrine reduced the loss in 14C from phospholipids and inhibited aggregation and formation of [14C]-TxA2. Thrombin-induced aggregation was accompanied by substantial loss of 14C from phospholipids and equivalent gains of 14C in free fatty acids and TxB2; mepacrine pretreatment caused partial inhibition of thrombin-induced aggregation, halved the net 14C loss from phospholipids, but had little effect on the appearance of 14C in TxB2. 6 It is concluded that in human platelets PGAP-induced dense granule release and irreversible aggregation are dependent on the liberation of arachidonate and its metabolism via prostaglandin endoperoxides to thromboxane, that PGAP and thrombin elicit mobilization of arachidonate from different pools of membrane phospholipids, and that the mechanism of PGAP-activation of human platelets differs from those of thrombin- and ADP-activation.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Brammer JP,Maguire MHdoi
10.1111/j.1476-5381.1984.tb16442.xsubject
Has Abstractpub_date
1984-05-01 00:00:00pages
61-72issue
1eissn
0007-1188issn
1476-5381journal_volume
82pub_type
杂志文章abstract::Following the discovery of the first effective antiviral compound (idoxuridine) in 1959, nucleoside analogues, especially acyclovir (ACV) for the treatment of herpesvirus infections, have dominated antiviral therapy for several decades. However, ACV and similar acyclic nucleosides suffer from low aqueous solubility an...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0706446
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The human kinome consists of roughly 500 kinases, including 150 that have been proposed as therapeutic targets. Protein kinases regulate an array of signalling pathways that control metabolism, cell cycle progression, cell death, differentiation and survival. It is not surprising, then, that new ...
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abstract::Almost all existing models for G-protein-coupled receptors (GPCRs) are based on the occurrence of monomers. Recent studies show that many GPCRs are dimers. Therefore for some receptors dimers and not monomers are the main species interacting with hormones/neurotransmitters/drugs. There are reasons for equivocal interp...
journal_title:British journal of pharmacology
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doi:10.1038/sj.bjp.0707571
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abstract::1. Recent studies have shown antagonists at the NK1 subtype of receptor for tachykinins are antiemetics and suggested that this may result from blockade of tachykinin-mediated synaptic transmission at a central site in the emetic reflex. 2. We have used intracellular recording in vitro to study the pharmacology of tac...
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doi:10.1038/sj.bjp.0701482
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abstract::1. Rat mesenteric (approximately 250 microns) were set up in a single-channel isometric myograph designed to allow with 6 microM fura-2AM for 2 h and simultaneous recordings of neurogenic contraction (force) and intracellular calcium [Ca2+]i were obtained. In other experiments, arteries were loaded with 1 microCi ml-1...
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doi:10.1038/sj.bjp.0701337
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0705472
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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...
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更新日期:2020-08-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:1992-04-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb10287.x
更新日期:1987-06-01 00:00:00
abstract::1 The influence of dopamine receptor agonists on gastric acid secretion stimulated by thyrotropin-releasing hormone (TRH) was studied in the perfused stomach of anaesthetized rats. 2 Intraventricular TRH produced a dose-dependent stimulation of basal gastric acid secretion. 3 Pretreatment with apomorphine, bromocripti...
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1983.tb10524.x
更新日期:1983-05-01 00:00:00
abstract::The complement system plays a major role in threat recognition and in orchestrating responses to microbial intruders and accumulating debris. This immune surveillance is largely driven by lectins that sense carbohydrate signatures on foreign, diseased and healthy host cells and act as complement activators, regulators...
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb12751.x
更新日期:1992-10-01 00:00:00
abstract::1 Palmitaldehyde, olealdehyde and linolealdehyde acetal phosphatidic acids induced rapid shape change and dose-dependent biphasic aggregation of human platelets in platelet-rich plasma; aggregation was reversible at low doses and irreversible at high doses of the acetal phosphatidic acids. The palmitaldehyde congener ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1983.tb10508.x
更新日期:1983-05-01 00:00:00
abstract::1. The effect of histamine H1-receptor stimulation on inositol phospholipid hydrolysis has been investigated in the hamster vas deferens smooth muscle cell line, DDT1MF-2. 2. Histamine (EC50 = 27 microM) stimulated the accumulation of [3H]-inositol phosphates in DDT1MF-2 cells prelabelled with [3H]-myo-inositol. 2-Thi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13462.x
更新日期:1993-01-01 00:00:00
abstract:LINKED ARTICLES:This article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc. ...
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1992.tb14446.x
更新日期:1992-08-01 00:00:00
abstract::1. Insulin antibodies were induced in young guinea-pigs of both sexes weighing 300-400 g and housed in a room maintained at 28 degrees C+/-2 degrees C, by subcutaneous injection of 2 ml of freshly prepared insulin antigen emulsion between the shoulders once every month.2. To estimate the titre of serum antibody the se...
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更新日期:1971-05-01 00:00:00
abstract::1. Vasoconstrictions induced by transmural electrical field stimulation were frequency-dependent from 2 to 32 Hz in the rabbit isolated splenic artery. All contractions were abolished in the presence of tetrodotoxin 1 microM or guanethidine 100 microM. Stimulation at a frequency of more than 32 Hz induced both neuroge...
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doi:10.1038/sj.bjp.0700933
更新日期:1997-02-01 00:00:00
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更新日期:2001-04-01 00:00:00
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更新日期:2003-05-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2005-04-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:1979-01-01 00:00:00
abstract::1 In the isolated basilar artery of the rabbit, gamma-aminobutyrate acid (GABA) (ED50 +/- s.e. mean, 2.4 +/- 1.1 x 10(-5) M) produced a relaxation, if the tone had been increased with 5-hydroxytryptamine (5-HT). 2 3-Aminoproprane sulphonic acid (3-APS) produced a similar, but smaller relaxation, while baclofen had no ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb08770.x
更新日期:1982-01-01 00:00:00
abstract::1. beta-Bungarotoxin and other snake toxins with phospholipase activity augment acetylcholine release evoked from mouse motor nerve terminals before they produce blockade. This action of the toxins is independent of their phospholipase A2 activity, but the underlying mechanism for the facilitation of release is unclea...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1988.tb11595.x
更新日期:1988-07-01 00:00:00