RENAL IMMUNOCYTOCHEMICAL DISTRIBUTION AND PHARMACOLOGICAL PROPERTIES OF THE DUAL ANGIOTENSIN-II AVP RECEPTOR

We have recently characterized a novel angiotensin II/vasopressin (Ang II/AVP) dual receptor coupled to adenylate cyclase and responding wit h equal sensitivity to Ang II and AVP. To gain insight into putative r enal physiological roles of the dual Ang II/AVP receptor, we determine d its pharmacological binding properties and renal immunocytochemical distribution. The effective displacement of [H-3]AVP by [1-deamino-Val (14),D-Arg(8)]-vasopressin (DVDAVP), a specific antidiuretic AVP analo gue, supports a V-2-type AVP receptor characteristic of the Ang II/AVP receptor. Displacement of I-125-Ang II by losartan but not by PD 1233 19 defines the Ang II/AVP receptor as a novel AT(1) receptor isoform c oupled to adenylate cyclase, in contrast to prototype Ca2+-mobilizing AT(1) receptors. Neither Ang II nor AVP displace each other, corrobora ting the predicted discrete binding domains for Ang II and AVP but pre senting an enigma for the dissection of putative Ang II-and AVP-specif ic hierarchical roles of the dual Ang II/AVP receptor. The renal cytol ocalization of the Ang II/AVP receptor to the outer medullary thick as cending limb tubules and inner medullary collecting ducts is consisten t with the well-established AVP stimulation of sodium and water reabso rption in these tubules. These data suggest that the Ang II/AVP recept or might provide the molecular basis for the observed similar stimulat ory effects of Ang II and AVP on renal tubular sodium and fluid reabso rption at physiological hormone concentrations.