CONCOMITANT ACTIVATION OF G(I) AND G(Q) PROTEIN-COUPLED RECEPTORS DOES NOT REQUIRE AN INCREASE IN CYTOSOLIC CALCIUM FOR PLATELET-AGGREGATION

U46619 is a potent platelet agonist, its binding to the thromboxane A( 2) receptor resulting in G(q)-binding protein-mediated responses; neve rtheless, it is unable to cause platelet aggregation, unless released ADP is present. In this study we demonstrate that G(i) activation is t he step U46619 lacks to cause platelet aggregation; in fact, when plat elets were heated with an ADP scavenger system, the response to U46619 was restored by the addition of epinephrine, which activates platelet s via a G(i) protein, The concomitant activation of G(i) and G(q) prot eins does not require increased cytosolic calcium to cause aggregation , as assessed by the fact that platelets treated with the intracellula r calcium chelator BAPTA were able to respond to U46619 provided ADP o r epinephrine was present. Moreover, as the calcium ionophore ionomyci n, at low concentrations, potentiated the response to U46619 but not t o epinephrine, me may conclude that calcium influx preferentially acti vates a G(i) downstream signalling pathway, (C) 1998 Federation of Eur opean Biochemical Societies.