Activation of V1-receptors by vasopressin stimulates inositol phospholipid hydrolysis and arachidonate metabolism in human platelets.
The activation of platelet V1-receptors by vasopressin (0.01-1 microM) induces the rapid formation of inositol phosphates, 1,2-diacylglycerol and phosphatidic acid, indicating inositol phospholipid hydrolysis by phospholipase C. Vasopressin immediately induces the formation of inositol bisphosphate and inositol trisphosphate. Accumulation of inositol 1-monophosphate and inositol 4-monophosphate occurs later after a time lag of 15 s. Low concentrations (10-100 nM) of vasopressin only activate phospholipase C, whereas high concentrations (1 microM) induce activation of phospholipase C and subsequently the production of arachidonate metabolites. Cyclo-oxygenase metabolites are associated with further activation of phospholipase C, release reaction and irreversible platelet aggregation. Vasopressin requires for its action extracellular Mg2+, but not Ca2+. The described platelet changes are not induced by 1-desamino-[8-D-arginine]vasopressin, a V2-receptor agonist, and are blocked by a specific V1-receptor antagonist. The results indicate that platelets possess a V1-receptor that is coupled to polyphosphoinositide hydrolysis by phospholipase C, leading to the formation of 1,2-diacylglycerol and inositol trisphosphate. Those compounds may act as second messengers for platelet responses induced by vasopressin, whereas endoperoxides and thromboxane A2 stimulated by vasopressin may serve as amplifiers for platelet activation.
D001091:Arachidonate Lipoxygenases; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors; D004075:Diglycerides / Q000097:blood; D006801:Humans; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000097:blood; D016859:Lipoxygenase Inhibitors; D008236:Lypressin / Q000494:pharmacology*; D010712:Phosphatidic Acids / Q000097:blood; D010716:Phosphatidylinositols / Q000097:blood*; D011945:Receptors, Angiotensin / Q000187:drug effects*; D011956:Receptors, Cell Surface / Q000187:drug effects*; D017483:Receptors, Vasopressin; D013268:Stimulation, Chemical
C011439:1,2-diacylglycerol; D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D004075:Diglycerides; D007295:Inositol Phosphates; D016859:Lipoxygenase Inhibitors; D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D011945:Receptors, Angiotensin; D011956:Receptors, Cell Surface; D017483:Receptors, Vasopressin; D016718:Arachidonic Acid; D008236:Lypressin; D001091:Arachidonate Lipoxygenases