THROMBOSIS RESEARCH 67; 479-489,1992 0049-3848/92 $5.00 + .OO Printed in the USA. Copyright (c) 1992 Pergamon Press Ltd. All rights reserved. PPACK-THROMBIN IS A NONCOMPETITIVE INHIBITORY OF a- THROMBIN BINDING TO HUMAN PLATELETS. A.H. Schmaier*, F.J. Meloni**, W. Nawarawong+, Y.P. Jiang* University of Michigan *, Ann Arbor, MI 48109, and Thomas Jefferson University**, Philadelphia PA 19107 and Temple University School of Medicine+, Philadelphia, PA 19 140 (Received 20.11.1991 accepted in revised form 29.51992 by Editor C.W. Francis) (Received by Executive Editorial Office 12.8.1992) ABSTRACT: Recent studies from our laboratory indicate that purified kininogens are noncompetitive inhibitors of human a- thrombin but not PPACK-thrombin, binding to human washed platelets. In order to understand the mechanism by which the kininogens inhibit a-thrombin binding,, investigations were initiated to determine if a-t hr om bin and PPACK-thrombin bound to the same site on human platelets. Initial investigations reveal that a-thrombin is a more potent inhibitor of 12SI-PPACK-thrombin binding than PPACK-thrombin. Further studies show that PPACK- thrombin is a noncompetitive inhibitor of 1251-a- thrombin binding to platelets. These studies suggest that human a-thrombin binds on the platelet surface to a different site or binds differently to the same site from PPACK-thrombin. These data indicate that the ability of the kininogens to block a-thrombin binding to platelets but not PPACK-thrombin binding results from these thrombins having either two different binding sites or one binding site on the platelet surface which they interact with differently. Key Words: a-thrombin, PPACK-thrombin, kininogen, platelets, thrombin receptor 479