ADP, ADRENALINE AND SEROTONIN STIMULATE INOSITOL 1,4,5-TRISPHOSPHATE PRODUCTION IN HUMAN PLATELETS

Although adenosine diphosphate (ADP) is a well-known stimulus of plate let aggregation, it is not the generally accepted view that ADP stimul ates phosphatidylinositolbisphosphate (PtdIns(4,5)P-2) hydrolysis. Usi ng a very sensitive competitive receptor binding assay for inositol 1, 4,5-trisphosphate (Ins(1,4,5)P-3), we have detected Lns(1,4,5)P-3 prod uction at early(< 10 s) time points after stimulation of human platele ts by the weak agonists ADP, adrenaline and serotonin (5-hydroxytrypta mine, 5-HT). When adrenaline or 5-HT was combined with ADP in the pres ence of aspirin, there was a significant potentiation of ADP-induced p latelet aggregation, but there was no potentiation of Ins(1,4,5)P-3 ge neration. Also, the increases in intracellular calcium (Ca2+) concentr ations stimulated by ADP were not potentiated by adrenaline in the pre sence of aspirin. Therefore, the synergism between the purinergic and adrenergic pathways of platelet activation occurs downstream from PtdI ns(4,5)P-2 hydrolysis and intracellular Ca2+ mobilization, although pr ior to platelet aggregation. (C) 1998 Elsevier Science B.V. All rights reserved.