Stimulations of arachidonate release and inositol-1,4,5-triphosphate formation are mediated by distinct G-proteins in human platelets.
Addition of fluoroaluminate to human platelet suspension stimulated thromboxane synthesis and inositol-1,4,5-triphosphate formation in a time and dose dependent manner. Neomycin inhibited markedly fluoroaluminate induced inositol-1,4,5-triphosphate formation without significantly affecting thromboxane synthesis. Preincubation of platelets with PGE1, also inhibited significantly inositol-1,4,5-triphosphate formation with modest reduction of thromboxane synthesis. On the contrary, pretreatment of platelets with pertussis toxin inhibited fluoroaluminate stimulated thromboxane synthesis without affecting inositol-1,4,5-triphosphate formation. Similarly, preincubation of platelets with phorbol ester, PMA, inhibited markedly thromboxane synthesis with modest reduction of inositol-1,4,5-triphosphate formation. These results indicate that inositol-1,4,5-triphosphate formation and arachidonate release and thromboxane synthesis are controlled separately and are mediated by different G-proteins which are coupled to phospholipase C and phospholipase A2 respectively in platelets.
D000535:Aluminum / Q000494:pharmacology; D017607:Aluminum Compounds; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology; D005459:Fluorides; D005461:Fluorine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000097:blood*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000097:blood*; D009355:Neomycin / Q000494:pharmacology; D037342:Pertussis Toxin; D012969:Sodium Fluoride / Q000494:pharmacology; D013403:Sugar Phosphates / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013929:Thromboxane B2 / Q000097:blood; D013931:Thromboxanes / Q000096:biosynthesis; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D017607:Aluminum Compounds; D001095:Arachidonic Acids; D007295:Inositol Phosphates; D013403:Sugar Phosphates; D013931:Thromboxanes; D010566:Virulence Factors, Bordetella; C050992:tetrafluoroaluminate; D016718:Arachidonic Acid; D005461:Fluorine; D013929:Thromboxane B2; D015544:Inositol 1,4,5-Trisphosphate; D012969:Sodium Fluoride; D000535:Aluminum; D011464:Epoprostenol; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D009355:Neomycin; D013755:Tetradecanoylphorbol Acetate; D005459:Fluorides