Effects of CV-3988, an antagonist of platelet-activating factor (PAF), on washed rabbit platelets

Platelet-activating factor (1-0-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine or AGEPC) is a small, extremely potent phospholipid mediator. CV-3988, a unique structural analogue of AGEPC, has recently been introduced as a selective antagonist of AGEPC-induced in vitro platelet activation and in vivo systemic hypotension. At concentrations greater than 5 X 10(-5) M, CV-3988 itself induced aggregation and secretion responses in washed rabbit platelets. CV-3988 inhibited AGEPC-induced platelet activation at concentrations as low as 10(-8) M, but also blocked platelet activation induced by collagen and calcium ionophore A23187 at concentrations between 10(-6) M and 10(-5) M. The mechanism of inhibition, however, did not depend on increased levels of intracellular 3',5'-cyclic adenosine monophosphate (cAMP). In fact, CV-3988, like AGEPC itself, appeared to lower cAMP levels in washed rabbit platelets.