Genetics of vasopressin receptors

Membrane receptors that couple to guanine nucleotide binding protein (GPCRs) represent one of the largest families of proteins in the genome. Because of their universal distribution and multiple actions, genetic variations of GPCRs are associated with various human diseases. For instance, the clinical phenotype of congenital nephrogenic diabetes insipidus has been linked to more than 155 loss-of-function putative mutations of the arginine vasopressin (AVP) V(2) receptor, which span each and every segment of this seven-transmembrane domain receptor. These mutant receptors, which are mostly trapped in the endoplasmic reticulum, can be rescued by membrane-permeant nonpeptidic AVP receptor antagonists. An overexpression of V(1)-vascular and V(3)-pituitary AVP receptors has been observed in some endocrine tumors. The single nucleotide polymorphism of AVP receptors in the context of complex genetic traits is currently being investigated, and preliminary findings have been reported in arterial hypertension and autism.