Concomitant activation of G(i) protein-coupled receptor and protein kinase C or phospholipase C is required for platelet aggregation

It has recently been suggested that the concomitant activation of two distinct G protein-coupled receptors (G(i) and G(q)) is essential for platelet aggregation: in fact, the thromboxane A₂ synthetic agonist, U46619, which causes the selective activation of G(q), is not able to elicit fibrinogen receptor exposure unless ADP or epinephrine is present. In the present study we demonstrate that a direct G(q) activation is not required for platelet aggregation and that the activation of an enzyme downstream of G(q), such as phospholipase C (PLC) or protein-kinase C (PKC), is sufficient for such a process. In fact, platelet aggregation occurred in response to the snake venom toxin convulxin, which activates the PLC isoform PLCγ2 or to cytosolic PKC activator phorbol 12-myristate 13-acetate (PMA) provided a G(i) protein-coupled receptor was activated by ADP or epinephrine. The evidence that the PKC inhibitor, Ro 31-8220 did not suppress platelet aggregation in response to convulxin plus ADP or epinephrine led us to conclude that PLC and PKC are both involved in platelet aggregation, although not concomitantly, provided a G(i) protein-coupled receptor is activated. Copyright (C) 1999 Federation of European Biochemical Societies.