Abstract
Use of Ca 2+ ionophores (e.g. ionophore A 23187) and Ca 2+ 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 ([Ca 2+] i) via both calcium influx and mobilization of intracellular stores. Treatment of washed human platelets with this Ca 2+ agonist resulted in typical Ca 2+-linked activation phenomena such as shape change and phosphorylation of M r 47 000 and M r 20 000 proteins. CGP 28392 also negatively influenced platelet cyclic AMP metabolism, and appears to exert this effect as a consequence of elevated [Ca 2+] i. The data suggest that the mechanisms of action of CGP 28392 involve dihydropyridine-susceptible structures on the cell membrane and intracellular Ca 2+ binding sites.
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