Non-steriodal anti-inflammatory drug-mediated regulation of COX-2 and EP3 receptor expression in the M-1 murine cortical collecting duct cell line.

Abstract

The cortical collecting duct (CCD) is a major site of intrarenal prostaglandin E2 (PGE2) synthesis. By indirect immunofluorescence using isoform specific antibodies, we have localized COX-1 and -2 immunoreactivity to all cell types of the murine M-1 CCD cell line. By, immunohistochemistry, both COX-1 and COX-2 were localized to the intercalated cells of the collecting duct on paraffin embedded mouse kidney sections. When COX enzyme activity was measured in the M-1 cells, both indomethacin (COX-1 and -2 inhibitor) and the specific COX-2 inhibitor NS-398 effectively blocked PGE2 synthesis. These results demonstrate that COX-2 is a major contributor to the pool of PGE2 synthesized by the CCD. PGE2 exerts predominantly diuretic and natriuretic effects upon the CCD. Our results which document the expression of COX-2 in the CCD provide a mechanism through which the newly developed class of COX-2 specific inhibitors could exert side effects with respect to the regulation of fluid and electrolyte homeostasis. (Abstract shortened by UMI.)