AN EXTRACELLULAR RESIDUE DETERMINES THE AGONIST SPECIFICITY OF V-2 VASOPRESSIN RECEPTORS

The specific V-2 agonist 1-deamino [8-D-arginine]vasopressin (dDAYP), used for treatment of central diabetes insipidus, binds to vasopressin V-2 receptors from human, bovine and rat kidney with an affinity that is similar to that of the natural hormone vasopressin, In contrast, t he V-1 receptors and the porcine V-2 receptor do not tolerate a D-argi nine in position 8 of vasopressin, By site directed mutagenesis of the cloned bovine and porcine V-2 receptors we identified a residue (Asp- 103) in the first extracellular loop of vasopressin receptors which is responsible for high affinity binding of dDAVP.