PLATELET THROMBIN RECEPTOR

THIS PHASE I RESEARCH WILL TEST THE HYPOTHESIS THAT GLYCOPROTEIN (GP) V IS THE THROMBIN RECEPTOR ON PLATELETS. RECENT DATA INDICATE THAT THROMBIN, ACTING PROTEOLYTICALLY AT A RECEPTOR ON THE PLATELET SURFACE, IS THE PHYSIOLOGICALLY IMPORTANT AGONIST TO ACTIVATE PLATELETS AND TO INITIATE ARTERIAL THROMBUS FORMATION. PREVIOUS STUDIES HAVE SHOWN THAT THE ONLY DETECTABLE THROMBIN SUBSTRATE ON THE PLATELET MEMBRANE SURFACE IS GP V. IN THIS STUDY, GP V WILL BE CLONED TO DEDUCE THE AMINO ACID SEQUENCE OF THIS PROTEIN. VARIOUS EXPRESSION SYSTEMS WILL BE USED TO DETERMINE WHETHER GP V IS THE THROMBIN RECEPTOR. PHASE II RESEARCH WILL DEVELOP AN INHIBITOR OF GP V HYDROLYSIS. SUCH AN INHIBITOR WILL FORM A NEW CLASS OF THERAPEUTIC AGENTS THAT RESTRICT THE FORMATION OF ARTERIAL THROMBOSIS BY INHIBITING THE PLATELET ACTIVATION PROCESS. THIS NEW CLASS OF DRUGS WILL BE MARKETED COMMERCIALLY AS AGENTS THAT WILL LIMIT THROMBUS FORMATION IN A VARIETY OF CLINICAL SITUATIONS, INCLUDING UNSTABLE ANGINA, THROMBOTIC STROKE, PATIENTS UNDERGOING ANGIOPLASTY AND FIBRINOLYSIS, AND PATIENTS AT RISK FOR CORONARY OCCLUSIONS.