Molecular pathogenesis of nephrogenic diabetes insipidus.
There have been significant advances recently in the understanding of the molecular causes of nephrogenic diabetes insipidus. The resistance of the collecting duct to the action of vasopressin in this disorder results from abnormalities in several of the intricate steps that mediate the increase in principal cell hydraulic conductivity in response to the hormone. In this article, we review the current understanding of the known genetic causes of nephrogenic diabetes insipidus that affect the binding of vasopressin to the V2 receptor and subsequent intracellular signaling events, as well as the translocation of aquaporin-2 water channels to the apical membrane. In addition, genetic diseases, which decrease collecting-duct water absorption by diminishing the interstitial medullary osmolarity, are discussed.
Division of Nephrology, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Room 7-155 Factor Building, Los Angeles, CA 90095, USA. mtnguyen@mednet.ucla.edu
Minhtri K
MK
Nguyen
Søren
S
Nielsen
Ira
I
Kurtz
D000818:Animals; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins / Q000235:genetics / Q000502:physiology; D001127:Arginine Vasopressin / Q000502:physiology; D018500:Diabetes Insipidus, Nephrogenic / Q000139:chemically induced / Q000235:genetics* / Q000628:therapy; D005786:Gene Expression Regulation; D008040:Genetic Linkage; D006801:Humans; D009154:Mutation; D017483:Receptors, Vasopressin / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D014960:X Chromosome
C496023:AQP2 protein, human; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin