Atrial natriuretic factor receptor subtypes in the rat central nervous system

Abstract

In this study we investigated the presence and anatomical location of atrial natriuretic factor (ANF) receptor subtypes in the rat central nervous system using in vitro autoradiographic and cross-linking techniques. 125I-ANF-(Ser99-Tyr126) served as a labeled ligand, whereas ANF-(Ser99-Tyr126) and two peptides endowed with selectivity for ANF-C receptor--namely, C-ANF (des-[Gln116-Gly120] ANF-[Asp102-Cys121]-NH2) and ANF-(Phe106-Ile113)-NH2--were used as displacing agents. Distribution studies revealed the presence of specific ANF binding sites in a number of central nervous system areas examined. C-ANF at 10(-6) M competed for 125I-ANF binding to a much lower extent than ANF in many of those structures, whereas ANF-(106-113)-NH2 at 10(-6) M did not have a significant effect on the radioligand binding except in the choroid plexus, pia-arachnoid, and olfactory bulb. Analysis of the competition curves revealed that in the choroid plexus, pia-arachnoid, olfactory bulb, subfornical organ, area postrema, and habenular nucleus, ANF interacts with its binding sites with high affinity (IC50, 0.46-0.77 nM). In contrast, C-ANF and ANF-(106-113)-NH2 competed for 125I-ANF binding with high potency (IC50, 2-16 nM) in the choroid plexus and pia-arachnoid only, where they were able to displace 60-70% of the radioligand binding. 125I-ANF cross-linking to olfactory bulb membranes resolved a specific 120-kDa band corresponding to the high molecular weight receptor but did not disclose a specifically labeled band corresponding to the low molecular mass receptor.(ABSTRACT TRUNCATED AT 250 WORDS)