Abstract
Human thrombin binds to specific receptors on the surface of human platelets in a manner analogous to bovine thrombin. Thus, two classes of binding are observed--high affinity with a dissociation constant (Kdiss) of 0.02 U/ml and low affinity with a Kdiss of 5 U/ml. Bovine and human thrombin bind to the same platelet receptors, although bovine thrombin binds with slightly greater affinity. When the amount of thrombin bound to platelets is related to the extent of 14C-serotonin release, bovine and human thrombin are equally effective. Antibodies to human and bovine thrombin were found to differ markedly in their ability to precipitate thrombin of the two species. Thus, antibovine thrombin precipitated eightfold more bovine thrombin than human thrombin, while antihuman thrombin precipitated tenfold more human thrombin than bovine thrombin. Similar differences were found in the ability of Fab fragments of these antibodies to block the interaction of thrombin of each species with human platelets. The finding that both species of thrombin, despite significant evolutionary differences in primary structure, retain essentially identical binding sites to platelets suggests that this part of the thrombin molecule is physiologically important and supports our hypothesis of a role for thrombin binding to platelets in platelet function and hemostasis.
