The role of calcium in the stimulation of prostaglandin synthesis by vasopressin in rabbit renal-medullary interstitial cells in tissue culture.
The role of Ca2+ in the stimulation of prostaglandin (PG) biosynthesis by vasopressin was investigated in rabbit renal-medullary interstitial cells in tissue culture. A decrease in extracellular Ca2+ to less than 25 microM did not affect basal PGE2 production, but inhibited PGE2 synthesis stimulated by vasopressin, angiotensin and the Ca2+ ionophore A23187 by 55, 65 and 95% respectively. The study of vasopressin-stimulated PGE2 synthesis in the absence of extracellular Ca2+ demonstrated that: (a) hormone-sensitive phospholipase activity was inhibited as measured by [3H]arachidonic acid release; (b) the maximal rate of vasopressin-stimulated activity was decreased without a change in the vasopressin concentration that evoked half-maximal stimulation of PGE2 synthesis; and (c) the Ca2+-channel blocker verapamil and the Ca2+-calmodulin antagonist trifluoperazine mimicked the inhibitory effects of removing extracellular Ca2+. These agents had no effect in the absence of Ca2+. In contrast with their effects on vasopressin action, neither the removal of extracellular Ca2+ nor the addition of verapamil altered the ability of hyperosmotic mannitol to increase PGE2 synthesis. These data are consistent with the hypothesis that a component of vasopressin-stimulated PGE2 biosynthesis involves the influx of extracellular Ca2+, followed by the activation of Ca2+-calmodulin-stimulated phospholipase(s).
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D046508:Culture Techniques; D015232:Dinoprostone; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism*; D011458:Prostaglandins E / Q000096:biosynthesis*; D011817:Rabbits; D013268:Stimulation, Chemical; D014268:Trifluoperazine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D011458:Prostaglandins E; D000804:Angiotensin II; D001127:Arginine Vasopressin; D014268:Trifluoperazine; D000001:Calcimycin; D014700:Verapamil; D015232:Dinoprostone; D002118:Calcium