Binding and functional effects of atrial natriuretic factor in isolated rat kidney.
A new methodological approach was developed to study the relationship between specific binding and dose-response curves of the renal effects of atrial natriuretic factor (ANF) in isolated perfused rat kidneys (IK). IK were perfused with 125I-labeled and unlabeled ANF 1-28 (4 pM to 1 microM) to determine the following: 1) distribution, capacity (Cmax), and apparent affinity (S50) of specific binding of ANF 1-28 in cortex, outer medulla, and papilla and 2) dose-response curves of the effects of ANF 1-28 on renal hemodynamics and excretion of fluid and electrolytes. The kidney had a very high density of high-affinity binding sites for ANF. Cortex had greater than 90% of total binding sites (Cmax = 6.8 pmol/g tissue; S50 = 54 pM), whereas papilla had less than 2% of total binding sites with a 10-fold lower apparent affinity (S50 = 860 pM) than in cortex. ANF-induced increases in glomerular filtration rate and excretion of fluid and electrolytes were detectable at 10-100 pM and maximal effects occurred at 1-10 nM ANF. Below 1 nM there was no dissociation between the renal hemodynamic and natriuretic effects of ANF. There was a close agreement between dose-response and binding curves of ANF to cortex. Results demonstrate that binding site occupancy in kidney cortex and renal effects of ANF occur at near physiological concentrations of the hormone.
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance
C472610:atrial natriuretic peptide, rat; D009320:Atrial Natriuretic Factor