The sea within us: disorders of body water homeostasis.
The use of a sensitive radioimmunoassay to measure plasma vasopressin led to the clarification of the role of vasopressin in most clinical hyponatremic states, an advance that had been impossible with the less sensitive bioassay for antidiuretic hormone. The cloning of the V2 vasopressin receptor on the basolateral membrane of the principal cells of the collecting duct demonstrated that the majority of congenital nephrogenic diabetes insipidus (NDI) was caused by mutations in this V2 receptor gene. The Nobel Prize discovery of the first membrane water channel by Agre and colleagues allowed for the molecular understanding of many disorders of water homeostasis, several of which are discussed in this review. Mutations of the vasopressin-regulated water channel on the principal cells of the collecting duct, namely aquaporin (AQP)2, account for a minority of cases of congenital NDI. Downregulation of AQP2 expression has subsequently proved important in an array of clinically significant causes of acquired NDI. Most important clinically, has been the discovery of several orally active, non-peptide V2 receptor antagonists, which have significant implications in the treatment of hyponatremic states. This review discusses the major advances that have increased our understanding of the mechanisms of renal water regulation in health and disease. The relationship between osmotic and non-osmotic regulation of antidiuretic hormone (arginine vasopressin) release is discussed.
Schrier
Robert W
RW
University of Colorado School of Medicine, Division of Renal Diseases and Hypertension, Department of Medicine, 4200 East Ninth Avenue B173, Denver, CO 80262, USA. Robert.Schrier@uchsc.edu
D000818:Animals; D001834:Body Water / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D006955:Hypernatremia / Q000503:physiopathology; D007010:Hyponatremia / Q000175:diagnosis / Q000503:physiopathology; D008954:Models, Biological; D015394:Molecular Structure; D017483:Receptors, Vasopressin / Q000502:physiology
D017483:Receptors, Vasopressin