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Regulation of Transcription of Renal Proximal Tubule Na,K‐ATPase by G‐Protein Coupled Receptors
Author(s) -
Taub Mary,
Springate James E,
Khrovi Sudha
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.602.20
Subject(s) - medicine , prostaglandin e2 receptor , receptor , endocrinology , chemistry , stimulation , dopamine , agonist , microbiology and biotechnology , biology
Our previous studies indicate that transcription of the Na,K‐ATPase beta subunit gene in MDCK cells is regulated by Prostaglandins, via 2 Prostaglandin Regulatory Elements (PGREs). In order to determine whether 1) our studies with MDCK have a broader physiologic significance, and 2) similar regulation occurs in the renal proximal tubule (RPT), transient transfection studies were conducted with primary rabbit RPT cells. When transfecting using pH ?1‐1141Luc, a beta subunit promoter/luciferase construct, we observed a stimulation by PGE 1 and PGE 2 , as well as the Gs‐coupled EP2 and EP4 receptor agonists butaprost and PGE 1 ‐OH (respectively). The PGE 1 stimulation was inhibited by the antagonists SC51089 and AH6909 (which block Gq coupled EP1 receptors). Na,K‐ATPase in the renal proximal tubule is regulated by epinephrine and dopamine, which, like PGE, act via G‐ Protein Coupled Receptors (GPCRs). Indeed, 1 µM epinephrine stimulated transcription, as well as the alpha 1 and beta agonists phenylephrine and isoprenaline, respectively. Similarly, dopamine was stimulatory, an effect which was inhibited both by the D1 and D2 receptor antagonists, SCH23390 and L741, 626, respectively. These results are consistent with previously reported chronic stimulatory effects of dopamine on renal Na,K‐ATPase (in addition to acute inhibition), and may be mediated transcriptionally via PGREs.