Vasopressin-stimulated phosphoinositide hydrolysis in cultured rat inner medullary collecting duct cells is mediated by the oxytocin receptor.
Studies were performed to identify the receptor that mediates AVP-stimulated phosphoinositide (PI) hydrolysis in cultured rat inner medullary collecting tubule (RIMCT) cells. While the selective V1 receptor agonist [Ho1, Phe2, Orn8] VT has no effect on inositol trisphosphate (IP3) production over the range of 10(-13)-10(-7) M, the selective V2 receptor agonist VDAVP stimulates IP3 production in dose-dependent fashion. Oxytocin stimulates IP3 production in dose-dependent fashion as well. AVP-stimulated phospholipase C activity is not inhibited by the V1 receptor antagonist d(CH2)5Tyr(Me)AVP(10(-7) M) but is eliminated by the V2 receptor antagonist d(CH2)5DTyr(Et)VAVP (10(-7) M). Similarly, the response to oxytocin is eliminated by the V2 receptor antagonist. The selective oxytocin receptor agonist [Thr4, Gly7] oxytocin does not stimulate cAMP production in RIMCT cells but does promote PI hydrolysis. The selective oxytocin receptor antagonist desGlyNH2d(CH2)5[Tyr(Me)-Thr4]OVT (10(-7) M) does not inhibit AVP-stimulated cAMP production but eliminates IP3 production in response to AVP or the V2 receptor agonist VDAVP. These studies demonstrate that AVP or a V2 receptor agonist stimulate PI hydrolysis in cultured RIMCT cells via occupancy of the oxytocin receptor.
Teitelbaum
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I
Department of Medicine, University of Colorado School of Medicine, Denver 80262.
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007679:Kidney Medulla / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D010121:Oxytocin / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011945:Receptors, Angiotensin / Q000187:drug effects* / Q000502:physiology*; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D010738:Type C Phospholipases / Q000378:metabolism*
D010716:Phosphatidylinositols; D011945:Receptors, Angiotensin; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D010121:Oxytocin; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D010738:Type C Phospholipases