An extracellular congenital nephrogenic diabetes insipidus mutation of the vasopressin receptor reduces cell surface expression, affinity for ligand, and coupling to the Gs/adenylyl cyclase system

Mol Endocrinol. 1994 Jul;8(7):886-94. doi: 10.1210/mend.8.7.7984150.


The mutation of the type-2 vasopressin receptor (V2R) apparently responsible for X-linked congenital nephrogenic diabetes insipidus (CNDI) in the Q3 family consists of a T to C transition in codon 113, causing the change of Arg-113 to Trp. Arg-113 is located in the putative first extracellular loop of the V2R next to a frequently conserved Cys thought to interact via a disulfide bridge with a Cys of the second extracellular loop. The present study explored whether this mutation may account for the CNDI phenotype. The mutation was excised from the genomic DNA of a Q3 patient and introduced into the V2R cDNA, which was then placed into an expression plasmid and transfected into COS cells for transient expression and murine L cells for stable expression. Studies with L cells expressing similar levels of wild type and Q3 receptors showed that the mutant receptor has a 20-fold reduced affinity for arginine vasopressin (AVP) and stimulates adenylyl cyclase with an EC50 that is increased by a factor of about 60-fold. The same shift in the EC50 for adenylyl cyclase stimulation was obtained when deamino[8-D-Arg]vasopressin was substituted for AVP. Studies with COS cells revealed that at equal levels of transfected DNA, the mutant receptor is expressed at lower levels (about 20%) than the wild type receptor, indicating that the mutation hinders the transport of the receptor to the cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylyl Cyclases / physiology*
  • Amino Acid Sequence
  • Animals
  • Arginine Vasopressin / metabolism*
  • Base Sequence
  • Cell Line
  • Cell Membrane / metabolism
  • Chlorocebus aethiops
  • Deamino Arginine Vasopressin / metabolism
  • Deamino Arginine Vasopressin / pharmacology
  • Diabetes Insipidus, Nephrogenic / genetics*
  • GTP-Binding Proteins / metabolism
  • Humans
  • L Cells
  • Mice
  • Molecular Sequence Data
  • Point Mutation*
  • Protein Binding
  • Protein Conformation
  • Protein Processing, Post-Translational
  • Receptors, Vasopressin / chemistry
  • Receptors, Vasopressin / genetics*
  • Receptors, Vasopressin / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction*


  • Receptors, Vasopressin
  • Recombinant Fusion Proteins
  • Arginine Vasopressin
  • GTP-Binding Proteins
  • Adenylyl Cyclases
  • Deamino Arginine Vasopressin