sta-2 and Hemorrhagic-Disorders

A platelet disorder characterized by the absence of thromboxane A2 (TXA2)-induced platelet aggregation is a new clinical entity of platelet dysfunction. The platelets of three patients had the ability to bind exogenous TXA2, but synthetic TXA2 mimetic-induced postreceptor biochemical events, such as IP3 formation, Ca2+ mobilization, phosphatidic acid formation, and GTPase activities, were selectively defective, suggesting impaired coupling between the TXA2 receptor and phospholipase C activation. Gene analysis of the TXA2 receptor showed a substitution of Leu for Arg60 in the first cytoplasmic loop in all patients, and this mutation seemed to be responsible for this platelet disorder.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Amino Acid Substitution; Animals; Blood Platelets; Calcimycin; Calcium Signaling; CHO Cells; Codon; Cricetinae; Cricetulus; DNA, Complementary; Enzyme Activation; GTP Phosphohydrolases; Hemorrhagic Disorders; Humans; Phosphatidic Acids; Phosphatidylinositol Diacylglycerol-Lyase; Platelet Aggregation; Point Mutation; Receptors, Thromboxane; Recombinant Proteins; Sodium Fluoride; Thromboxane A2; Transfection; Type C Phospholipases