Changes in tissue sensitivity to vasopressin in hereditary hypothalamic diabetes insipidus

Specific binding of (125I) arg8-vasopressin to mononuclear phagocytes of the circulating blood was studied in 3 patients (one male, two females) with hereditary hypothalamic diabetes insipidus before, during and after therapy with 1-desamino-8-D-arginine vasopressin and compared with values of 15 normal donors (7 males, 8 females). Before therapy specific radioligand binding activity was considerably increased (0.3 +/- 0.08 fmoles/2.2 X 10(5) cells/ml) versus controls (0.23 +/- 0.04 fmoles/2.2 X 10(5) cells/ml). Increased binding was due to increase in receptor concentration per cell. In contrast, during treatment and after withdrawal of therapy the receptor binding activity was 0.1 +/- 0.05 fmoles/2.2 X 10(5) cells/ml. The dissociation constant (KD) for hormone binding before therapy (25 +/- 0.2 pM) was roughly identical with that of normal donors (24 +/- 0.8 pM), indicating insignificant changes in receptor affinity. During treatment and 48 h after withdrawal of therapy, however, the KD value was 11 +/- 0.45 pM, which amy be accounted for by an elevation in the binding affinity. We conclude that untreated patients with hereditary hypothalamic diabetes insipidus have increased tissue sensitivity to vasopressin, but have decreased binding capacity during and even two days after discontinuation of therapy, possibly as the result of 1-desamino-8-D arginine vasopressin-induced desensitization phenomena.