EPIDERMAL GROWTH-FACTOR ANTAGONIZES VASOPRESSIN IN-VIVO AND IN-VITRO

Since EGF causes diuresis through a renal action and may antagonize th e 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) ev ery 12 hours for days 5 to 16. All ewes received an i.v. isotonic sali ne infusion (100 ml/day) for days 1 to 8 and days 13 to 16, and i.v. E GF in 100 ml saline/day at doses of 0 (N = 8) or 10 (N = 8) mu g/hr fo r 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 negativ e fluid balance, kaliuresis and a transient natriuresis (all P < 0.05) . When EGF treatment ceased, the effects of DDAVP treatment alone grad ually became apparent. From the in vitro studies, the AVP-related pept ides displaced specific AVP V-1- and V-2-receptor antagonist radio-lig ands from rat renal inner medullary membranes, whereas EGF had no effe ct. However, EGF antagonized AVP V-2-stimulated cAMP production in a d ose-dependent way (IC50 = 2 x 10-(7) M). Therefore, the diuretic effec t of EGF is not via direct antagonism of the antidiuretic AVP V-2-rece ptor but seems mediated by inhibition of the antidiuretic AVP V-2-rece ptor second messenger system.