OXYTOCIN AS AN ANTIDIURETIC-HORMONE .2. ROLE OF V-2 VASOPRESSIN RECEPTOR

We conducted this study to determine what receptor mediates the effect of oxytocin to increase osmotic water permeability (P-f) in the rat inner medullary collecting duct (IMCD). Reverse transcription-polymerase chain reaction (RT-PCR) experiments demonstrated that mRNA for both the oxytocin receptor and the V-2 receptor is present in the rat terminal IMCD. In isolated perfused IMCD segments, we found that the V-2 vasopressin receptor antagonist [d(CH2)(5)(1),D-Ile(2),Ile(4),Arg(8)]vasopressin, but not oxytocin receptor antagonists, blocked the hydrosmotic response to 200 pM oxytocin. The selective oxytocin receptor agonist [Thr(4),Gly(7)]oxytocin did not increase water permeability. Oxytocin also increased urea permeability in IMCD segments. Studies in IMCD suspensions showed that oxytocin increases adenosine 3',5'-cyclic monophosphate production in a dose-dependent fashion with a half-maximal (EC(50)) response at 5.2 nM. The dose-response curves were virtually identical for IMCD suspensions from Sprague-Dawley rats and Brattleboro rats. The oxytocin dose-response curve was displaced to the right of the vasopressin dose-response curve (EC(50), 0.44 nM). From these results, we conclude that the V-2 receptor mediates the hydrosmotic action of oxytocin in rat IMCD.