Vasopressin induces V1 receptors to activate phosphatidylinositol- and phosphatidylcholine-specific phospholipase C and stimulates the release of arachidonic acid by at least two pathways in the smooth muscle cell line, A-10.
The rat thoracic aortic smooth muscle cell line, A-10, expresses vasopressin receptors of the V1 subtype. Vasopressin treatment of these cells stimulated the release of arachidonic acid and the formation of diacylglycerol and phosphocholine. These responses to vasopressin were inhibited by the V1-specific antagonist SK&F 100273, indicating that these were receptor-mediated phenomena. The mechanisms by which V1 receptors mediate arachidonic acid release appeared to be unaffected by cycloheximide or actinomycin D, suggesting that the release is independent of protein and RNA synthesis. The V1 receptors also appeared to be coupled to a phospholipase C which can hydrolyze phosphatidylcholine, a possible source of the released arachidonic acid. Phosphocholine and diacylglycerol were also generated. The release of arachidonic acid, phosphocholine, or diacylglycerol was not affected by prior treatment of the cells with pertussis toxin (islet-activating protein). Thus, the release of these second messengers is not mediated by the guanine nucleotide-binding protein Gi or other pertussis toxin-sensitive substrates. We conclude that V1 receptors induce the release of arachidonic acid and the formation of diacylglycerol and phosphocholine via the activation of both a phosphatidylinositol- and phosphatidylcholine-specific phospholipase C.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001127:Arginine Vasopressin / Q000494:pharmacology; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D050356:Lipid Metabolism; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D037342:Pertussis Toxin; D010713:Phosphatidylcholines / Q000378:metabolism; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism*; D017483:Receptors, Vasopressin; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism*; D014667:Vasopressins / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D001095:Arachidonic Acids; D010713:Phosphatidylcholines; D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D010566:Virulence Factors, Bordetella; D014667:Vasopressins; D001127:Arginine Vasopressin; D003609:Dactinomycin; D016718:Arachidonic Acid; D003513:Cycloheximide; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins