Regulation of renal proximal tubule Na-K-ATPase by prostaglandins

(PGs) play a number of roles in the kidney, including regulation of salt and water reabsorption. In this report, evidence was obtained for stimulatory effects of PGs on Na-K-ATPase in primary cultures of rabbit renal proximal tubule (RPT) cells. The results of our real-time PCR studies indicate that in primary RPTs the effects of PGE2, the major renal PG, are mediated by four classes of PGE (EP) receptors. The role of these EP receptors in the regulation of Na-K-ATPase was examined at the transcriptional level. Na-K-ATPase consists of a catalytic -subunit encoded by the ATP1A1 gene, as well as a -subunit encoded by the ATP1B1 gene. Transient transfection studies conducted with pH1-1141 Luc, a human ATP1B1 promoter/lucif-erase construct, indicate that both PGE1 and PGE2 are stimulatory. The evidence for the involvement of both the cAMP and Ca2 signaling pathways includes the inhibitory effects of the myristolylated PKA inhibitor PKI, the adenylate cyclase (AC) inhibitor SQ22536, and th