The stimulatory effect of PGE(1) on the activity of the Na,K-ATPase in MDCK cells is associated with all increase in the rate of transcription of the Na,K-ATPase beta 1 subunit gene and an increase in the rate of biosyntliesis of the Na,K-ATPase [M.L. Taub, Y. Wang, I.S. Yang, P. Fiorella, S.M. Lee, Regulation of the Na,K-ATPase activity of Madin-Darby canine kidney cells in defined medium by prostaglandin El and 8-bromocyclic AMP, J. Cell. Physiol. 151 (1992) 337-346]. In order to further define the molecular mechanisms, transient transfection and biosynthesis studies were conducted with dibutyryl cAMP resistant (DBr) MDCK cells, defective in cAMP dependent protein kinase, and PGE(1) independent (PGE(1) Ind) MDCK cells with elevated intracellular cAMP. Transient transfection studies with the human NaX-ATPase beta 1 promoter/luciferase construct, pH beta 1-1141 Luc [J. Feng, J. Orlowski, J.B. Linerel, Identification of a functional thyroid hormone response element in the upstream flanking region of the human Na,K-ATPase beta I gene, Nucleic Acids Res. 21 (1993) 2619-2626], showed that the stimulatory effect of PGE(1) and 8Br-cAMP on beta 1 subunit gene transcription is retained in the DBr and PGE(1) independent variants. However, the stimulatory effect of PGE(1) and 8Br-cAMP on Na,K-ATPase biosynthesis was lost in DBr (unlike PGE(1) Ind) variants. These results can be explained by a defect in post-transcriptional regulation. (c) 2006 Elsevier Inc. All rights reserved.