Leupeptin selectively inhibits human platelet responses induced by thrombin and trypsin; a role for proteolytic activation of phospholipase C.
Thrombin and trypsin induce serotonin release and aggregation in human platelets. Both proteases induce activation of phospholipase C as reflected by formation of inositol phosphates and phosphorylation of the resultant 1,2-diacylglycerol to phosphatidic acid. Also, thrombin and trypsin activate protein kinase C and myosin light chain kinase as indicated, respectively, by phosphorylation of the 40,000 and 20,000 dalton proteins. Leupeptin, a known inhibitor of serine proteases, blocks all the observed responses of human platelets to trypsin and thrombin. Leupeptin does not inhibit serotonin release and aggregation induced by other platelet stimuli such as collagen, platelet-activating factor, ionophore A23187, and arachidonic acid. The implication of a proteolytic-mediated pathway in the transmembrane signalling involved in platelet activation is discussed.
D000328:Adult; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000096:biosynthesis; D007976:Leupeptins / Q000494:pharmacology*; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology*; D010712:Phosphatidic Acids / Q000096:biosynthesis; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects; D012701:Serotonin / Q000097:blood; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014357:Trypsin / Q000494:pharmacology*; D014361:Trypsin Inhibitors; D010738:Type C Phospholipases / Q000097:blood*
D007295:Inositol Phosphates; D007976:Leupeptins; D009842:Oligopeptides; D010712:Phosphatidic Acids; D014361:Trypsin Inhibitors; D012701:Serotonin; D010738:Type C Phospholipases; D014357:Trypsin; D013917:Thrombin; C032854:leupeptin