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Functional Receptors in the Avian Kidney for C-Type Natriuretic Peptide

Max-Planck-Institute for Physiological and Clinical Research, W. G. Kerckhoff-Institute, Parkstrasse 1, D-61231 Bad Nauheim, Germany

Address all correspondence and requests for reprints to: Rüdiger Gerstberger, Ph.D., W.G. Kerckhoff-Institute, MPI, Parkstrasse 1 D-61231 Bad Nauheim, Germany. E-mail: rgerst{at}kerckhoff.mpg.de

Renal actions of avian-specific C-type natriuretic peptide (chCNP) were investigated in the conscious Pekin duck. Under conditions of steady-state renal water and salt elimination, systemic chCNP administration (6 and 30 pmol/min·kg BW for 20 min) dose dependently induced transient natriuresis and diuresis. Mean arterial pressure and heart rate remained constant throughout the experiment. Employing receptor autoradiography, binding sites specific for [¹²⁵I]BH-chCNP could be localized at high density in glomeruli of both reptilian- and mammalian-type nephrons, and arterioles of the avian kidney. The distal tubular zone revealed [¹²⁵I]BH-chCNP binding sites at medium, the medullary cone area at low density. Using an enriched kidney membrane fraction, competitive displacement studies with [¹²⁵I]BH-chCNP as radioligand and various unlabeled peptide analogs (chANP, chCNP, rANP, rBNP, frANP, rANP_(4–23)) allowed the discrimination of high-affinity (IC₅₀ values 10^-10–10^-9 M) and low-affinity (IC₅₀ values 10^-8–10^-7 M) binding sites different from typical mammalian receptor subtypes. Intracellular cyclic GMP formation could be demonstrated immunocytochemically for both types of glomeruli and cells of the distal tubular zone in fixed tissue sections after in vivo application of chCNP (0.8 nmol/min·kg BW; 5 min). The results obtained by combination of physiological in vivo studies and in vitro receptor analysis indicate an important role for chCNP in the modulation of avian kidney function.