Hereditary vasopressin resistance in man and mouse.
The DI +/+ Severe hereditary nephrogenic diabetes insipidus mouse is resistant to the antidiuretic action of vasopressin (VP) because of failure to accumulate cAMP and subsequent inability to form intramembranous particles on the apical (luminal) surface of kidney cells that normally respond to VP. The defect is primarily, if not exclusively, due to excessive activity of specific cAMP-phosphodiesterases. The abnormality can be overcome in vitro and in vivo by the phosphodiesterase inhibitor, rolipram. Most cases of hereditary NDI in man have sex-linked recessive inheritance, which appears to be due to an abnormality of the V2 receptor. The chromosomal locus of the defect is Xq28. Sporadic cases of congenital NDI have been described in females who appear to have a defect beyond the V2 receptor and the guanine nucleotide-binding stimulatory protein. There is no information on the biochemical defect in very rare cases with other types of inheritance patterns. No abnormalities of V1a and V1b receptor function have been found in patients with NDI. Mice and patients with NDI have evidence of increased AVP synthesis. AVP release in relation to plasma osmolality is increased in patients during infusion of hypertonic saline. This is the opposite of what has been described in patients with primary polydipsia (dipsogenic diabetes insipidus) who are chronically overhydrated. Together, these studies indicate that chronic dehydration and overhydration can cause up- and downregulation of the osmotic release of AVP.
Moses
A M
AM
Department of Medicine, SUNY Health Science Center, Syracuse 13210.
Scheinman
S J
SJ
D000818:Animals; D001127:Arginine Vasopressin / Q000502:physiology*; D003919:Diabetes Insipidus / Q000151:congenital / Q000235:genetics* / Q000662:veterinary; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D007671:Kidney Concentrating Ability; D051379:Mice; D010904:Pituitary Gland, Posterior / Q000503:physiopathology; D012376:Rodent Diseases / Q000503:physiopathology
D001127:Arginine Vasopressin