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Type: Journal article
Title: ADP, adrenaline and serotonin stimulate inositol 1,4,5-triphosphate production in human platelets.
Author: Vanags, D.
Lloyd, J.
Rodgers, S.
Bochner, F.
Citation: European Journal of Pharmacology, 1998; 358(1):93-100
Issue Date: 1998
ISSN: 0014-2999
Statement of
Daina M. Vanags, John V. Lloyd, Susan E. Rodgers and Felix Bochner
Abstract: Although adenosine diphosphate (ADP) is a well-known stimulus of platelet aggregation, it is not the generally accepted view that ADP stimulates phosphatidylinositolbisphosphate (PtdIns(4,5)P2) hydrolysis. Using a very sensitive competitive receptor binding assay for inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), we have detected Ins(1,4,5)P3 production at early (<10 s) time points after stimulation of human platelets by the weak agonists ADP, adrenaline and serotonin (5-hydroxytryptamine, 5-HT). When adrenaline or 5-HT was combined with ADP in the presence of aspirin, there was a significant potentiation of ADP-induced platelet aggregation, but there was no potentiation of Ins(1,4,5)P3 generation. Also, the increases in intracellular calcium (Ca2+) concentrations stimulated by ADP were not potentiated by adrenaline in the presence of aspirin. Therefore, the synergism between the purinergic and adrenergic pathways of platelet activation occurs downstream from PtdIns(4,5)P2 hydrolysis and intracellular Ca2+ mobilization, although prior to platelet aggregation.
Keywords: Blood Platelets; Humans; Calcium; Epinephrine; Inositol 1,4,5-Trisphosphate; Serotonin; Aspirin; Adenosine Diphosphate; Platelet Aggregation Inhibitors; Platelet Aggregation; Drug Synergism
Description: Copyright © 1998 Elsevier Science B.V.
RMID: 0030003404
DOI: 10.1016/S0014-2999(98)00595-0
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Appears in Collections:Pharmacology publications

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