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 μM) to determine the following: 1) distribution, capacity (C(max)), 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 >90% of total binding sites (C(max) = 6.8 pmol/g tissue; S₅₀ = 54 pM), whereas papilla had <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 effect of ANF occur at near physiological concentrations of the hormone.