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Title: Epidermal growth factor antagonizes vasopressin in vivo and in vitro.
Austin Authors: Phillips, P A;Grant, Sharon L;Davidson, A F;Risvanis, John;Stephenson, J;Gow, Paul J 
Affiliation: Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Australia
Issue Date: 1-Apr-1994
Publication information: Kidney International; 45(4): 1028-36
Abstract: 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 V2-receptor agonist (1-desamino, D-Arg8 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 100 ml saline/day at doses of 0 (N = 8) or 10 (N = 8) micrograms/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 < 0.05). When EGF treatment ceased, the effects of DDAVP treatment alone gradually became apparent. From the in vitro studies, the AVP-related peptides displaced specific AVP V1- and V2-receptor antagonist radioligands from rat renal inner medullary membranes, whereas EGF had no effect. However, EGF antagonized AVP V2-stimulated cAMP production in a dose-dependent way (IC50 = 2 x 10(-7) M). Therefore, the diuretic effect of EGF is not via direct antagonism of the antidiuretic AVP V2-receptor but seems mediated by inhibition of the antidiuretic AVP V2-receptor second messenger system.
Gov't Doc #: 8007572
Type: Journal Article
Subjects: Animals
Arginine Vasopressin.metabolism
Cyclic AMP.metabolism
Deamino Arginine Vasopressin.antagonists & inhibitors
Diuresis.drug effects
Dose-Response Relationship, Drug
Epidermal Growth Factor.pharmacology
Kidney.drug effects
Osmolar Concentration
Rats, Sprague-Dawley
Receptors, Vasopressin.metabolism
Second Messenger Systems
Water-Electrolyte Balance
Appears in Collections:Journal articles

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