ATRIAL-NATRIURETIC-PEPTIDE INHIBITS MINERALOCORTICOID RECEPTOR FUNCTION IN RAT COLONIC SURFACE CELLS

Atrial natriuretic peptide (ANP) inhibits and aldosterone (ALDO) stimu lates Na conductive transport. Therefore, the effects of ANP and its s econd messenger cGMP on mineralocorticoid receptor (MR) function in ra t colon surface and crypt cells were examined. 100 nM 8-Br-cGMP decrea sed surface [H-3]ALDO binding by 42+/-4% but increased crypt [H-3]ALDO binding by 52+/-16%. ANP decreased surface [H-3]ALDO binding by simil ar to 50% after a 2.5-h lag period but had no effect on crypt ALDO bin ding, ANP and cGMP rapidly (< 15 min) inhibited surface cell ALDO-indu ced MR nuclear translocation but did not affect crypt MR nuclear trans location. Inhibition of cGMP-dependent protein kinase with KT5823 bloc ked the inhibitory effects of ANP and 8-Br-cGMP on surface cell ALDO b inding and MR nuclear translocation. In crypt, KT5823 increased baseli ne [H-3]ALDO binding but did not inhibit the stimulatory effect of exo genous cGMP, DEAE-cellulose chromatography and gel mobility shift assa y showed that ANP did not inhibit surface MR activation, ANP inhibited ALDO stimulated short circuit current in distal colon, These data dem onstrate cell-specific regulation of MR function, In surface cells, AN P rapidly inhibits MR nuclear translocation and ALDO-induced short cir cuit current, ANP inhibition of MR function may be an additional mecha nism of ANP antagonism of Na reabsorption.