Cloning and Characterization of a Vasopressin V2 Receptor and Possible Link to Nephrogenic Diabetes Insipidus

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Title: Cloning and Characterization of a Vasopressin V2 Receptor and Possible Link to Nephrogenic Diabetes Insipidus
Authors: Lolait, Stephen J.; O'Carroll, Anne-Marie; McBride, O. Wesley; Konig, Monica; Morel, Alain; Brownstein, Michael J.
Publisher: Nature
Date Published: May 28, 1992
Reference Number: 304
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The antidiuretic effect of arginine vasopressin (AVP) is mediated by renal-type (V2) receptors linked to adenylyl cyclase. We report here the cloning of the rat kidney V2 AVP receptor complementary DNA that encodes a 370-amino-acid protein with a transmembrane topography characteristic of G protein-coupled receptors, and with similarity to the V1a (hepatic) AVP receptor in its seven membrane-spanning domains. Expression of the cloned cDNA in mammalian cells showed specific ligand binding and activity characteristic of the native V2 AVP receptor. The receptor messenger RNA is detected only in the kidney. The human V2 receptor gene has been localized to the long arm of the X chromosome close to the locus for nephrogenic diabetes insipidus, an X-linked recessive disorder characterized by renal resistance to the antidiuretic action of AVP.

This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)

Lolait, et al., succeeded in cloning a rat kidney full length cDNA encoding the vasopressin V2 receptor. That is, they isolated a DNA species corresponding to the product of the rat receptor gene that could be used to synthesize receptor protein.

They then introduced this DNA into cultured cells and looked at the properties of the newly synthesized receptor. As expected, it was able to bind the antidiuretic hormone, arginine vasopressin, and when it did this, it stimulated the production of a metabolic regulator called cAMP. This molecule is responsible for the effects of receptor on cellular processes. In kidney cells, cAMP acts to close water channels, blocking water outflow.

At the time the V2 receptor cDNA was identified, it was already known that a gene responsible for NDI was located on the X chromosome in the Xq27-Xq28 region. Since it seemed likely that mutations in the V2 receptor gene could cause NDI, Lolait and his co-workers decided to look at the chromosomal location of the gene. As they suspected, it was found at Xq28, and they suggested that it was a strong candidate to be the NDI gene. Subsequently, they showed—as did members of several other laboratories—that mutations in the coding region of the V2 receptor gene segregated with NDI in families.