Platelet activation by alpha-thrombin is a receptor-mediated event.
Computer-assisted data analysis of binding isotherms (LIGAND) has shown that human platelets have binding sites for alpha-thrombin of high (Kd 0.3 nM), moderate (Kd 10 nM), and low affinities (Kd 3 microM). Application of similar techniques has shown that TLCK-thrombin does not, whereas PPACK-thrombin does, bind to the high-affinity binding site accessible to alpha-thrombin, but that both bind to the moderate and low-affinity sites. Treatment of platelets with Serratia marcescens protease destroys the high-affinity site but does not affect moderate-affinity binding. In accordance with this model, both modified thrombins compete with alpha-thrombin for platelet activation at the moderate-affinity site, but only PPACK-thrombin competes at the high-affinity site. These results establish that platelet activation by either low or moderate concentrations of thrombin are receptor-mediated events and explain the paradox of the differential effects of TLCK-thrombin on the binding and activation of platelets by alpha-thrombin.
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008970:Molecular Weight; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology*; D018179:Receptors, Thrombin; D012701:Serotonin / Q000378:metabolism; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000502:physiology*; D014107:Tosyllysine Chloromethyl Ketone / Q000494:pharmacology
D000590:Amino Acid Chloromethyl Ketones; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; C038145:prolyl-phenylalanyl-arginine chloromethyl ketone; D014107:Tosyllysine Chloromethyl Ketone; D012701:Serotonin; D013917:Thrombin