Derivatives of somatic cell hybrids which carry the human gene locus for nephrogenic diabetes insipidus (NDI) express functional vasopressin renal V2-type receptors.
The gene responsible for familial vasopressin-resistant nephrogenic diabetes insipidus (NDI) has been localized to a small region of the human X-chromosome (Xq28). A series of hamster lung fibroblast and mouse lymphocyte cell lines carrying fragments of the wild type human X-chromosome was analyzed for vasopressin renal-type V2 receptor expression, to test the hypothesis that the NDI locus may have identity with the V2 receptor gene. V2 receptor binding activity and induction of cAMP production in response to [Arg8] vasopressin (AVP) were exhibited by all cell lines carrying the wild type NDI locus, in contrast to control cell lines. AVP stimulation of cAMP production was concentration-dependent and could be almost completely inhibited by co-incubation with a V2-V1 receptor-specific antagonist. The V2-specific agonist [Mpa1,Val4,Sar7]AVP was as potent as AVP in inducing cAMP production by NDI-DNA-carrying cells, whereas no response was shown to other hormones such as calcitonin, oxytocin (less than 10(-8) M), isoproterenol, or an oxytocin-specific agonist. All results were consistent with the hypothesis that the V2 receptor gene co-localized with the NDI locus, supporting the view that the loci are one and the same.
Jans
D A
DA
Max-Planck-Institut für Biophysik, Frankfurt, Federal Republic of Germany.
van Oost
B A
BA
Ropers
H H
HH
Fahrenholz
F
F
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D003919:Diabetes Insipidus / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006822:Hybrid Cells / Q000187:drug effects / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D011224:Prazosin / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000235:genetics* / Q000378:metabolism; D017483:Receptors, Vasopressin
D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D000242:Cyclic AMP; D011224:Prazosin