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 (<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.