A role of contractile proteins in the mechanism of platelet-aggregation

Abstract

Recently, it has been reported that metabolites of arachidonic acid in platelets play an important role in the first step of thrombus formation and that prost-acyclin, one of metabolites of arachidonic acid in vascular walls inhibits platelet-aggregation. However, it is still unknown how the above metabolites of arachidonic acid are involved in platelet-aggregation.In this paper, inhibitory mechanisms of platelet-aggregation by vascular walls were studied by using bovine carotid arteries. It has been reported that prostacyclin produced by vascular walls could elevate the intracellular cyclic AMP and that some agents which elevate the cyclic AMP have an inhibitory effect on platelet-aggregation. On the other hand, some substances which are Ca++-chelators, such as EGTA inhibit the platelet-aggregation. Then, the effect on platelet-aggregation of Verapamil which was thought to inhibit Ca++-influx was studied. And, it was investigated if the elevation of intracellular cyclic AMP might have any effects on a behavior of the intracellular Ca++, by using subcellular fractions from human platelets.The results obtained in this paper were as follows: 1) Microsomes from bovine carotid arteries inhibited collageninduced platelet-aggregation by producing PGI2. 2) Verapamil inhibited the collagen-induced platelet-aggregation. 3) Platelets incubated with both arterial microsomes and Verapamil, each of which alone was not enough to inhibit the collagen-induced platelet-aggregation, could not be aggregated. 4) Cyclic AMP level in platelets incubated with both the arterial microsomes and Verapamil was higher than that incubated with either of them. 5) The cyclic AMP-stimulated calcium uptake by subcellular membranous components was closely correlated with their cyclic AMP-stimulated endogenous phosphorylation.In summary, it is suggested that the intracellular calcium ion of platelets with anti-aggregating agents may be too low to activate the calcium sensitive contractile protein for the thrombus formation.