Glucocorticoid regulation of genes in the amiloride-sensitive sodium transport pathway by semicircular canal duct epithelium of neonatal rat.

The lumen of the inner ear has an unusually low concentration of endolymphatic Na+, which is important for transduction processes. We have recently shown that glucocorticoid receptors (GR) stimulate absorption of Na+ by semicircular canal duct (SCCD) epithelia. In the present study, we sought to determine the presence of genes involved in the control of the amiloride-sensitive Na+ transport pathway in rat SCCD epithelia and whether their level of expression was regulated by glucocorticoids using quantitative real-time RT-PCR. Transcripts were present for alpha-, beta-, and gamma-subunits of the epithelial sodium channel (ENaC); the alpha1-, alpha3-, beta1-, and beta3-isoforms of Na+-K+-ATPase; inwardly rectifying potassium channels [IC50 of short circuit current (Isc) for Ba2+: 210 microM] Kir2.1, Kir2.2, Kir2.3, Kir2.4, Kir3.1, Kir3.3, Kir4.1, Kir4.2, Kir5.1, and Kir7.1; sulfonyl urea receptor 1 (SUR1); GR; mineralocorticoid receptor (MR); 11beta-hydroxysteroid dehydrogenase (11beta-HSD) types 1 and 2; serum- and glucocorticoid-regulated kinase 1 (Sgk1); and neural precursor cell-expressed developmentally downregulated 4-2 (Nedd4-2). On the other hand, transcripts for the alpha4-subunit of Na+-K+-ATPase, Kir1.1, Kir3.2, Kir3.4, Kir6.1, Kir6.2, and SUR2 were found to be absent, and Isc was not inhibited by glibenclamide. Dexamethasone (100 nM for 24 h) not only upregulated the transcript expression of alpha-ENaC (approximately 4-fold), beta2-subunit (approximately 2-fold) and beta3-subunit (approximately 8-fold) of Na+-K+-ATPase, Kir2.1 (approximately 5-fold), Kir2.2 (approximately 9-fold), Kir2.4 (approximately 3-fold), Kir3.1 (approximately 3- fold), Kir3.3 (approximately 2-fold), Kir4.2 (approximately 3-fold), Kir7.1 (approximately 2-fold), Sgk1 (approximately 4-fold), and Nedd4-2 (approximately 2-fold) but also downregulated GR (approximately 3-fold) and 11beta-HSD1 (approximately 2-fold). Expression of GR and 11beta-HSD1 was higher than MR and 11beta-HSD2 in the absence of dexamethasone. Dexamethasone altered transcript expression levels (alpha-ENaC and Sgk1) by activation of GR but not MR. Proteins were present for the alpha-, beta-, and gamma-subunits of ENaC and Sgk1, and expression of alpha- and gamma-ENaC was upregulated by dexamethasone. These findings are consistent with the genomic stimulation by glucocorticoids of Na+ absorption by SCCD and provide an understanding of the therapeutic action of glucocorticoids in the treatment of Meniere's disease.

Citation

Satyanarayana R Pondugula, Nithya N Raveendran, Zuhal Ergonul, Youping Deng, Jun Chen, Joel D Sanneman, Lawrence G Palmer, Daniel C Marcus. Glucocorticoid regulation of genes in the amiloride-sensitive sodium transport pathway by semicircular canal duct epithelium of neonatal rat. Physiological genomics. 2006 Jan 12;24(2):114-23

Mesh Tags

Substances

PMID: 16263802

search → result