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Research Article

A Low Affinity Vasopressin V2-Receptor in Inherited Nephrogenic Diabetes Insipidus

, , , , &
Pages 351-368 | Published online: 26 Sep 2008
 

Abstract

Congenital nephrogenic diabetes insipidus (NDI) is an X-linked inherited disorder characterized by renal resistance to the antidiuretic hormonal action of vasopressin. This study describes the molecular basis of nephrogenic diabetes insipidus in a dog family. Kidney membranes prepared from NDI-affected male huskies were examined for vasopressin binding and response. Compared to membranes from unaffected canines, those from the kidney inner medulla of NDI-dogs possessed normal V2-receptor numbers, but with 10–fold lower affinity for [Arg8] vasopressin (AVP). Adenylate cyclase stimulation by AVP in contrast to that by forskolin or GTP-analogues was similarly reduced in a dose responsive manner. The NDI-affected dogs showed antidiuretic responses to very high doses of V2–specific agonists, consistent with their possessing V2–receptors of lower affinity. Prolonged treatment with V2–agonists, 1–deamino [D-Arg8] VP (dDAVP) and 1–deamino [Va]4, Sar7] AVP (dVSAVP), rendered the NDI-affected dogs near normal in terms of water intake and urine osmolality.

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