AJP - Renal Physiology, Vol 253, Issue 5 917-F928, Copyright © 1987 by American Physiological Society
Binding and functional effects of atrial natriuretic factor in isolated rat kidney
M. Suzuki, F. A. Almeida, D. R. Nussenzveig, D. Sawyer and T. Maack
Department of Physiology, Cornell University Medical College, New York, New York 10021.
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.
