LOCALIZATION OF ATRIAL-NATRIURETIC-PEPTIDE RECEPTORS IN THE RAT TONGUE AND HARD PALATE

Atrial natriuretic peptide (ANP) receptors were characterized in rat o ral mucosa using quantitative in vitro autoradiography and activation of particulate guanylyl cyclase (GC) by natriuretic peptides. Competit ion-binding analysis performed by quantitative in vitro autoradiograph y demonstrated specific [I-125]rANP((1-28)), binding sites in the tong ue and hard palate. The precise location of this binding was revealed on the basal and parabasal cells of the epithelia by microautoradiogra phy. The dissociation constant (K-d) and maximal binding capacity (B-m ax) of these sites were 3.34 +/- 1.35 nM and 2.71 +/- 2.21 fmol/mm(2) on the epithelium of the tongue, and 4.09 +/- 1.52 nM and 3.45 +/- 3.0 1 fmol/mm(2) on the epithelium of the hard palate, respectively. Recep tor subtypes were characterized by competition with des [Gln(18), Ser( 19), Gly(20), Leu(21), Gly(22)] ANP((4-23)) (C-ANP), a specific ligand for the clearance receptor (NPR-C). These binding sites were displace d by C-ANP with inhibition constant (K-i) of 8.96 +/- 3.18 nM and B-ma x of 2.89 +/- 2.45 fmol/mm(2) on the epithelium of the tongue, and K-i of 9.12 +/- 2.71 nM and B-max of 3.08 +/- 2.94 fmol/mm(2) on the epit helium of the hard palate, respectively. Production of cyclic GMP by p articulate GC in the epithelial membranes of the tongue and hard palat e was stimulated by rANP((1-28)), porcine brain natriuretic peptide (B NP)((1-26)), and C-type natriuretic peptide (CNP)((1-22)) in a dose-de pendent manner. These results indicate that ANP-binding sites in the e pithelium of the tongue and hard palate are mainly clearance receptors (NPR-C) but biological receptors (NPR-A and/or NPR-B) with GC activit y are also present, and suggest that ANP may have a role in the prolif eration of the oral epithelial cells, especially in the tongue and har d palate. (C) 1998 Elsevier Science Ltd. All rights reserved.