THROMBIN RECEPTOR ACTIVATING PEPTIDE DOES NOT STIMULATE PLATELET PROCOAGULANT ACTIVITY

Platelets after challenge with alpha-thrombin alone, collagen alone or thrombin/ collagen mixture were observed to increase the rate of acti vation of prothrombin by factor Xa in the presence of factor Va and ca lcium ion (platelet procoagulant activity) by a maximum of 25, 45 and 110 fold, respectively. The increase in platelet procoagulant activity due to these agonists has been described previously and arises from i ncreased expression of phosphatidylserine on the platelet surface. Whe n platelets were treated with the thrombin receptor activating peptide (TRAP) (SFLLRNPNDKYEPK), alone or in the presence of collagen or thro mbin, no change in platelet procoagulant activity was observed at conc entrations of TRAP sufficient to cause increased intracellular calcium levels and protein phosphorylation in a manner similar to that of thr ombin. In addition, no increase in platelet procoagulant activity was seen upon treatment with TRAP in the presence of inactivated thrombin (PPACK-thrombin). These results suggest that the thrombin-mediated inc rease in procoagulant activity may be due to activation of a thrombin receptor distinct from the recently cloned G-protein-coupled receptor, or to other proteolytic events on the platelet surface. (C) 1994 Acad emic Press, Inc.