A low-affinity vasopressin V2-receptor gene in a kindred with X-linked nephrogenic diabetes insipidus.
In this study, a mutation in vasopressin Type 2 receptor (V2R) in a patient with hereditary nephrogenic diabetes insipidus (NDI) has been identified and characterized. The sequencing of the V2R gene from the patient revealed that there was a missense mutation (TAT to TGT) resulting in the substitution of 205Tyr for Cys in the putative third extracellular domain. The expression analysis in COS cells showed that the binding affinity of the mutant receptor (KD = 19.8 nM) for arginine vasopressin was much lower than that of the wild-type receptor (KD = 1.8 nM) so that intracellular cAMP production stimulated by arginine vasopressin was impaired in cells with the mutant V2R. From these results, it was concluded that the single amino-acid substitution of V2R is responsible for this familial disease.
Yokoyama
K
K
First Department of Medicine, Osaka University School of Medicine, Japan.
Yamauchi
A
A
Izumi
M
M
Itoh
T
T
Ando
A
A
Imai
E
E
Kamada
T
T
Ueda
N
N
D000328:Adult; D001127:Arginine Vasopressin / Q000378:metabolism / Q000494:pharmacology; D001483:Base Sequence; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D004252:DNA Mutational Analysis; D018500:Diabetes Insipidus, Nephrogenic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010375:Pedigree; D017354:Point Mutation; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D012076:Renal Agents / Q000378:metabolism / Q000494:pharmacology; D014960:X Chromosome
D017483:Receptors, Vasopressin; D012076:Renal Agents; D001127:Arginine Vasopressin; D000242:Cyclic AMP