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 VI receptor agonist [Ho', Phe', Orn8J VT has no effect on inositol trisphosphate (IP3) production over the range of 10-i3_10-7 M, the selective V2 receptor agonist VDAVP stimu- lates IP3 production in dose-dependent fashion. Oxytocin stimu- lates IP3 production in dose-dependent fashion as well. AVP- stimulated phospholipase C activity is not inhibited by the V, receptor antagonist d(CHA)5Tyr(Me)AVP (10-7 M) but is elimi- nated by the V2 receptor antagonist d(CH2)TDTyr(Et)VAVP (10-7 M). Similarly, the response to oxytocin is eliminated by the V2 receptor antagonist. The selective oxytocin receptor ago- nist rThr4, Gly71 oxytocin does not stimulate cAMP production in RIMCT cells but does promote PI hydrolysis. The selective oxytocin receptor antagonist desGlyNH2d(CH2)5[Tyr(Me)-Thr410VT (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. (J. Clin. Invest. 1991 . 87 :2122-2126.) Key words: vasopressin * oxytocin * phospholipase C * RIMCT cells thereby increase cytosolic Ca2' in several renal epithelia. These include the LLC-PK, cell (1-3), the rabbit cortical collecting duct (4), and the rat inner medullary collecting duct (5, 6). However, the identity ofthe receptor responsible for mediating this effect is controversial. In one study in LLC-PKI cells, the oxytocin receptor has been implicated (1), while in other stud- ies elimination ofthe response to AVP by a V, receptor antago- nist suggested that the AVP V, receptor is responsible (2, 3). Similar results supporting a role for the V1 receptor have been