Inhibition of thrombin-induced platelet aggregation by a derivative of wheat germ agglutinin. Evidence for a physiologic receptor of thrombin in human platelets.

We have prepared a nonagglutinating derivative of wheat germ agglutinin by cyanogen bromide treatment of the lectin and used it as a probe to study the thrombin-platelet interaction. The lectin derivative inhibited platelet aggregation by thrombin while aggregation induced by collagen. ristocetin, adenosine diphosphate. wheat germ agglutinin, or trypsin was not significantly affected. Under similar conditions, the secretion of serotonin by thrombin was blocked by the derivative. The inhibitory action of the derivative on thrombin-induced platelet aggregation could be overcome by increasing the thrombin concentration. A Schild plot of these data yielded a slope of 1 .0 and an apparent dissociation constant of 1 .0 M. Thus. the inhibition of thrombin-induced platelet aggregation by the denyative fits a model of competitive inhibition. Control expeniments showed that the lectin derivative acted on platelets and not on thrombin. However, the binding of (12 ] hrombin to platelets was not affected. Isolated platelet membranes were solubilized and passed through a column of the lectin derivative coupled to Sephanose. After exten-