The influence of CGP 28392, a 1,4-dihydropyridine, on human platelet calcium and cyclic AMP metabolism.

Use of Ca2+ ionophores (e.g. ionophore A 23187) and Ca2+ channel antagonists (e.g. dihydropyridines, phenylalkamines) has provided some insight into the molecular events involved in platelet activation. Recent structural modification of dihydropyridines has generated a novel class of compounds (e.g. CGP 28393) which apparently exert opposing functional effects. We report that CGP 28392 induced an elevation in free intracellular calcium concentrations [( Ca2+]i) via both calcium influx and mobilization of intracellular stores. Treatment of washed human platelets with this Ca2+ agonist resulted in typical Ca2+-linked activation phenomena such as shape change and phosphorylation of Mr 47 000 and Mr 20 000 proteins. CGP 28392 also negatively influenced platelet cyclic AMP metabolism, and appears to exert this effect as a consequence of elevated [Ca2+]i. The data suggest that the mechanisms of action of CGP 28392 involve dihydropyridine-susceptible structures on the cell membrane and intracellular Ca2+ binding sites.