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[Vasopressin (ADH)].

A Hirai¹, D Uchida, S Yoshida

¹2nd Department of Internal Medicine, Chiba University Medical School.

Nihon Rinsho. Japanese Journal of Clinical Medicine

|December 1, 1992

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Recent advances in vasopressin receptor molecular biology include cloning of V1a and V2 receptors. Novel antagonists, OPC-21268 and OPC-31260, show potential for treating cardiovascular disorders and SIADH.

Area of Science:

Molecular endocrinology
Receptor pharmacology
Renal physiology

Context:

Vasopressin (arginine vasopressin) is crucial for water-electrolyte balance and renal hemodynamics.
Significant progress has been made in understanding vasopressin receptor molecular biology.
Previous research identified the roles of vasopressin in physiological regulation.

Purpose:

To report the cloning of complementary DNA (cDNA) for rat liver V1a and kidney V2 arginine vasopressin receptors.
To describe the characteristics of the cloned receptors and their messenger RNA (mRNA) distribution.
To review the development and potential applications of novel vasopressin receptor antagonists.

Summary:

The V1a receptor cDNA encodes a protein with seven transmembrane domains, found in tissues expressing V1a receptors.

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The V2 receptor cDNA encodes a G protein-coupled receptor, with its mRNA detected exclusively in the kidney.

Orally active antagonists OPC-21268 (V1 antagonist) and OPC-31260 (V2 antagonist) have been developed.

Impact:

OPC-21268 inhibits vasopressin-induced vasoconstriction, suggesting potential for hypertensive cardiovascular disorders.
OPC-31260 inhibits the antidiuretic action of vasopressin, indicating utility in treating SIADH.
These findings advance the understanding of vasopressin signaling and pave the way for new therapeutic strategies.