Epidermal growth factor antagonizes vasopressin in vivo and in vitro

Epidermal growth factor antagonizes vasopressin in vivo and in vitro . Since EGF causes diuresis through a renal action and may antagonize the hydroosmotic effect of AVP in vitro we investigated the antagonistic action of EGF with AVP in vivo and the mechanism of the antagonism in vitro . Conscious ewes received i.m. injections of a selective AVP V 2 -receptor agonist (1-desamino, D-Arg 8 vasopressin acetate, DDAVP) every 12 hours for days 5 to 16. All ewes received an i.v. isotonic saline infusion (100 ml/day) for days 1 to 8 and days 13 to 16, and i.v. EGF in 100ml saline/day at doses of 0 (N = 8) or 10 (N = 8) µg/hr for days 9 to 12. DDAVP reduced both urine volume and water intake, and increased urine osmolality. In contrast, simultaneous infusion of EGF reversed the DDAVP-induced responses, resulting in a transient negative fluid balance, kaliuresis and a transient natriuresis (all P in vitro studies, the AVP-related peptides displaced specific AVP V 1 and V 2 -receptor antagonist radioligands from rat renal inner medullary membranes, whereas EGF had no effect. However, EGF antagonized AVP V 2 -stimulated cAMP production in a dose-dependent way (IC 50 = 2x 10 −7 M). Therefore, the diuretic effect of EGF is not via direct antagonism of the antidiuretic AVP V 2 -receptor but seems mediated by inhibition of the antidiuretic AVP V 2 -receptor second messenger system.