DIFFERENT ATP EFFECTS ON NATRIURETIC PEPTIDE RECEPTOR SUBTYPES IN LLC-PK1 AND NIH-3T3 CELLS

We have observed different ATP interactions in two guanylate cyclase ( GC)-coupled natriuretic peptide (NP) receptor subtypes, designated NPR -A and NPR-B. The NPR-A is selectively expressed by LLC-PK1 epithelial cells and the NPR-B by NIH-3T3 fibroblast cells. In LLC-PK1 membranes , ATP-Mg2+ potentiated ANP-stimulated GC activity (ANP-s-GC). In contr ast, in NIH-3T3 membranes, ATP-Mg2+ inhibited ANP-s-GC but enhanced CN P-stimulated GC activity (CNP-s GC). ATP in the presence of Mn2+ inhib ited LLC-PK1 and NIH-3T3 membrane ANP-s-GC and CNP-s-GC. These are the first data suggesting that the ATP-Mg2+ produces different effects be tween membrane NPR-A and -B subtypes. We have also demonstrated that G C of NPR-B is sensitive to methylene blue.