RENAL RECEPTORS FOR ATRIAL AND C-TYPE NATRIURETIC PEPTIDES IN THE RAT

Receptors for alpha-atrial natriuretic peptide (alpha-ANP) and C-type natriuretic peptide [CNP-(1-22)] were quantified in kidneys from adult Wistar rats by in vitro autoradiography. I-125-labeled alpha-ANP (100 pM) bound reversibly to glomeruli, outer medullary vasa recta, and inner medulla with an apparent dissociation constant (K(d)) of 3-6 nM. The presence of 10-mu-M des-[Gln18,Ser19,Gly20,Leu21,Gly22]ANP-(4-23) (C-ANP), a specific ligand of the ANPR-C subtype of alpha-ANP receptor, inhibited approximately 50% of the glomerular binding of I-125-alpha-ANP, and this moiety of glomerular binding was also inhibited by CNP-(1-22) with an apparent inhibitory constant (K(i)) of 10.47 +/- 7.59 nM. C-ANP and CNP-(1-22) showed little affinity for the medullary binding sites of alpha-ANP. I-125-[Tyr0]CNP-(1-22) (110 pM) bound solely to glomeruli and was competitively displaced by increasing concentrations of [Tyr0]CNP-(1-22) with an apparent K(d) of 1.42 +/- 0.48 nM. Binding of increasing concentrations (25 pM to 1 nM) of I-125-[Tyr0]CNP-(1-22) in the presence or absence of 1-mu-M [Tyr0]CNP-(1-22) also demonstrated a high affinity (K(d) of 0.41 +/- 0.07 nM) for the glomerular binding of I-125-[Tyr0]CNP-(1-22). Bound I-125-[Tyr0]CNP-(1-22) could be displaced by excess alpha-ANP and excess CNP-(1-22), both with high affinities. The glomerular binding of I-125-[Tyr0]CNP-(1-22) was also prevented by 10-mu-M C-ANP. Guanosine 3',5'-cyclic monophosphate produced by isolated glomeruli was measured by radioimmunoassay. Alpha-ANP increased production powerfully, but CNP-(1-22) caused only a slight stimulation with much lower affinity. These results suggest that Wistar rat kidneys express detectable quantities of the ANPR-C and ANPR-A but not the ANPR-B subtypes of natriuretic peptide receptor.