Interaction between epidermal growth factor and arginine vasopressin in renal medullary membranes.
1. Epidermal growth factor is a potent mitogen that causes natriuresis, diuresis and inhibition of arginine vasopressin-induced water reabsorption. 2. The aim of this study was to determine any interaction between epidermal growth factor and the V1 (vascular) and/or V2 (antidiuretic) arginine vasopressin receptor subtypes. 3. Radioligand binding displacement assays demonstrated that although arginine vasopressin related peptides displaced both radioligands from renal medullary membranes at low concentrations epidermal growth factor displaced neither. 4. Arginine vasopressin V2 receptor second messenger cyclic adenosine monophosphate (cAMP) production was inhibited by epidermal growth factor (IC50 2 x 10(-7) mol/L) as was sodium fluoride cAMP production but only at much higher concentrations. 5. Therefore the diuretic effect of epidermal growth factor is not via direct antagonism of arginine vasopressin receptors but seems mediated via inhibition of the V2 second messenger system.
Grant
S L
SL
Department of Medicine, University of Melbourne, Austin Hospital, Victoria, Australia.
Phillips
P A
PA
Gow
C B
CB
D000262:Adenylyl Cyclases / Q000378:metabolism / Q000502:physiology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology*; D001667:Binding, Competitive; D000242:Cyclic AMP / Q000096:biosynthesis; D004347:Drug Interactions; D004815:Epidermal Growth Factor / Q000502:physiology*; D005260:Female; D007679:Kidney Medulla / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000378:metabolism / Q000502:physiology; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology
D017483:Receptors, Vasopressin; D000804:Angiotensin II; D001127:Arginine Vasopressin; D004815:Epidermal Growth Factor; D000242:Cyclic AMP; D000262:Adenylyl Cyclases