Urodilatin binds to and activates renal receptors for atrial natriuretic peptide.
Urodilatin is a recently described member of the atrial natriuretic peptide family, thought possibly to be synthesized in the kidney. To determine if urodilatin binding sites are present in rat and human kidney, we evaluated the effect of urodilatin on iodine-125-labeled atrial natriuretic peptide (ANP) (100 pM) binding to tissue sections using an in situ autoradiographic technique. 125I-ANP binding occurred primarily in glomeruli and medullary structures of both rat and human kidney. Increasing concentrations of urodilatin yielded a monophasic displacement of 125I-ANP binding with an IC50 of 4.2 nM, a value nearly identical to that achieved with unlabeled ANP (7.2 nM). In additional experiments, rat glomeruli and inner medullary collecting duct cells were isolated and incubated in vitro with either ANP or urodilatin (10(-11) to 10(-6) M) and cyclic guanosine-3',5'-monophosphate accumulation measured by radioimmunoassay. Dose-response curves for the two peptides were superimposable in each tissue; at 10(-6) M, ANP generated 613 +/- 41 and urodilatin 603 +/- 55 fmol cyclic guanosine monophosphate per 10 minutes per milligram protein in inner medullary collecting duct cells (p = NS). Thus, urodilatin is as effective as ANP in displacing 125I-ANP binding to both rat and human renal tissue and in generating cyclic guanosine monophosphate in renal target cells in the rat, suggesting that its physiological effects may occur through the same receptors and signaling pathways that mediate the actions of ANP.
Valentin
J P
JP
Division of Nephrology, San Francisco General Hospital, CA 94110.
Sechi
L A
LA
Qui
C
C
Schambelan
M
M
Humphreys
M H
MH
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism* / Q000494:pharmacology*; D001345:Autoradiography; D001667:Binding, Competitive; D006152:Cyclic GMP / Q000378:metabolism*; D004232:Diuretics / Q000378:metabolism* / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism; D007679:Kidney Medulla / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017461:Receptors, Atrial Natriuretic Factor / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D004232:Diuretics; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; C056452:Ularitide; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP