[Vasopressin receptors: structure/function relationships and signal transduction in target cells].

Vasopressin, a hypothalamic hormone, acts on its target tissues via three different G protein coupled receptors. The vasopressin V1a and V1b receptors, associated to Gq protein and phospholipase C, are responsible for vasoconstriction and regulation of the corticotroph axis respectively. The V2 vasopressin receptor is coupled to Gs protein and adenylyl cyclase and is responsible for water reabsorption in the renal collecting duct. Mutations of the V2 receptor are involved in diabetes insipidus and most of these mutations result in an endoplasmic reticulum (ER) retention of the mutated receptor. With the V1b receptor model, we have identified a proximal sequence of the C-terminal segment, which is crucial for ER export. Mutations in this short domain result in ER accumulation and degradation of the receptor. SSR 149415, a nonpeptide antagonist of V1bR, which is permeable to cell membrane, is able to rescue the mutant phenotype and acts as a pharmacological chaperone.