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(Hypertension. 1997;29:957-961.)
© 1997 American Heart Association, Inc.

Articles

Renal Immunocytochemical Distribution and Pharmacological Properties of the Dual Angiotensin II/AVP Receptor

Carlos B. Gonzalez; Victoria L. M. Herrera; ; Nelson Ruiz-Opazo

From the Section of Molecular Genetics (N.R.-O., V.L.M.H.) and Cardiology (V.L.M.H.), Whitaker Cardiovascular Institute and Evans Department of Medicine, Boston (Mass) University School of Medicine, and Department of Physiology, Austral University, Valdivia, Chile (C.B.G.).

Correspondence to Nelson Ruiz-Opazo, PhD, Section of Molecular Genetics, Whitaker Cardiovascular Institute, Center for Advanced Biomedical Research, Boston University Medical School, 700 Albany St, W-609, Boston, MA 02118-2394.

Abstract We have recently characterized a novel angiotensin II/vasopressin (Ang II/AVP) dual receptor coupled to adenylate cyclase and responding with equal sensitivity to Ang II and AVP. To gain insight into putative renal physiological roles of the dual Ang II/AVP receptor, we determined its pharmacological binding properties and renal immunocytochemical distribution. The effective displacement of [³H]AVP by [1-deamino-Val¹⁴,D-Arg⁸]-vasopressin (DVDAVP), a specific antidiuretic AVP analogue, supports a V₂-type AVP receptor characteristic of the Ang II/AVP receptor. Displacement of ¹²⁵I–Ang II by losartan but not by PD 123319 defines the Ang II/AVP receptor as a novel AT₁ receptor isoform coupled to adenylate cyclase, in contrast to prototype Ca²⁺-mobilizing AT₁ receptors. Neither Ang II nor AVP displace each other, corroborating the predicted discrete binding domains for Ang II and AVP but presenting an enigma for the dissection of putative Ang II–and AVP-specific hierarchical roles of the dual Ang II/AVP receptor. The renal cytolocalization of the Ang II/AVP receptor to the outer medullary thick ascending limb tubules and inner medullary collecting ducts is consistent with the well-established AVP stimulation of sodium and water reabsorption in these tubules. These data suggest that the Ang II/AVP receptor might provide the molecular basis for the observed similar stimulatory effects of Ang II and AVP on renal tubular sodium and fluid reabsorption at physiological hormone concentrations.

Key Words: renin-angiotensin system • membrane proteins • sodium • water-electrolyte balance

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