Role of macromolecular binding site of thrombin molecule in excitation of anticoagulation system.
The reaction of anticoagulation system upon perfusion of humorally isolated (with retained innervation) carotid sinus of a rabbit by alpha-,beta/gamma-, DIP-alpha-thrombin and prethrombin I was studied. DIP-alpha-thrombin without clotting activity was shown to initiate like alpha-thrombin the reflex reaction of anticoagulation system characterized by a sharp increase in non-enzymatic fibrinolysis (by 225%) and total fibrinolytic activity of blood (by 51%). Prethrombin I (thrombin precursor) is also capable of exciting the function of anticoagulation system characterized by an increase in non-enzymatic fibrinolysis (by 82%) and total fibrinolytic activity (by 36%). Furthermore, perfusion of prethrombin I or alpha-thrombin at almost the same molar concentrations resulted in the similar degree of anticoagulation system effector reaction. Reflex response of anticoagulation system was not observed upon perfusion of carotid sinus by beta/gamma-thrombin that has high esterase but little if any clotting activity that appears to be due to molecular changes in the macromolecular binding site region. These data support the suggestion that the effect of anticoagulation system excitation is due to interaction of the macromolecular binding site in the structure of alpha-thrombin with anticoagulation system chemoreceptors.
D000818:Animals; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D002346:Carotid Sinus / Q000378:metabolism / Q000502:physiology; D002417:Cattle; D004792:Enzyme Precursors / Q000494:pharmacology; D005342:Fibrinolysis; D006493:Heparin / Q000378:metabolism; D046911:Macromolecular Substances; D011487:Protein Conformation; D011516:Prothrombin / Q000494:pharmacology; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018179:Receptors, Thrombin; D013917:Thrombin / Q000494:pharmacology*
D004792:Enzyme Precursors; D046911:Macromolecular Substances; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; D011516:Prothrombin; D006493:Heparin; C012007:prethrombins; D013917:Thrombin