Pathogenesis of a bleeding disorder characterized by platelet unresponsiveness to thromboxane A2.
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.
Fuse
I
I
First Department of Internal Medicine, Niigata University School of Medicine, Japan. fuse@med.niigata-u.ac.jp
Higuchi
W
W
Aizawa
Y
Y
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D019943:Amino Acid Substitution; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D016466:CHO Cells; D000001:Calcimycin / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D003062:Codon / Q000235:genetics; D006224:Cricetinae; D003412:Cricetulus; D018076:DNA, Complementary / Q000235:genetics; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006474:Hemorrhagic Disorders / Q000235:genetics*; D006801:Humans; D010712:Phosphatidic Acids / Q000096:biosynthesis; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010974:Platelet Aggregation / Q000187:drug effects*; D017354:Point Mutation; D017482:Receptors, Thromboxane / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D012969:Sodium Fluoride / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism
D003062:Codon; D018076:DNA, Complementary; D010712:Phosphatidic Acids; D017482:Receptors, Thromboxane; D011994:Recombinant Proteins; D000001:Calcimycin; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C037866:STA 2; D012969:Sodium Fluoride; D010738:Type C Phospholipases; D020558:GTP Phosphohydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase