Distribution of atrial natriuretic peptide receptor subtypes in rat brain

The presence and distribution of atrial natriuretic peptide (ANP) clearance receptors in rat brain were investigated by use of des[Gln18,Ser19,Gly20,Leu21,Gly22]ANP-(4-2 3) (C-ANP), a specific ligand of this receptor, to displace bound alpha-125I-labeled ANP. alpha-125I-ANP (200 pM) bound significantly to arachnoid mater, subfornical organ, choroid plexus, area postrema, median preoptic nucleus, and supraoptic and paraventricular nuclei. Binding was reversible at all sites with unlabeled alpha-ANP. Binding dissociation constants for alpha-ANP were measured for the first three sites and were all in the nanomolar range. C-ANP competed with alpha-125I-ANP only for binding sites on arachnoid mater, 1 microM C-ANP displacing radioligand from at least 60% of these sites. No alpha-125I-ANP was displaced by completely unrelated peptides. The reversible binding of 125I-Tyr0-ANP-(5-25), another relatively selective ligand of the clearance receptor, was also concentrated on arachnoid mater. Therefore, high-affinity binding sites for alpha-ANP on arachnoid mater may be clearance receptors for ANP.