1. Gamma-melanocyte stimulating hormone regulates the expression and cellular localization of epithelial sodium channel in inner medullary collecting duct cells.
- Author
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Cope G, Kaushik G, O'Sullivan SM, and Healy V
- Subjects
- Animals, Cell Line, Culture Media, Cyclic AMP metabolism, Epithelial Cells cytology, Epithelial Cells drug effects, Epithelial Sodium Channels metabolism, Gene Expression Regulation, Immediate-Early Proteins genetics, Immediate-Early Proteins metabolism, Ion Transport, Kidney Tubules, Collecting cytology, Kidney Tubules, Collecting drug effects, Mice, Natriuresis genetics, Osmolar Concentration, Protein Serine-Threonine Kinases genetics, Protein Serine-Threonine Kinases metabolism, Receptor, Melanocortin, Type 3 genetics, Receptor, Melanocortin, Type 3 metabolism, Signal Transduction, Sodium metabolism, alpha-MSH analogs & derivatives, alpha-MSH pharmacology, gamma-MSH metabolism, Epithelial Cells metabolism, Epithelial Sodium Channels genetics, Kidney Tubules, Collecting metabolism, gamma-MSH genetics
- Abstract
Gamma(2)-melanocyte-stimulating hormone (γ2MSH) is a peptide hormone released by the pituitary gland which is thought to act directly on the renal inner medulla to promote increased sodium excretion into urine (natriuresis). The aim of this study was to determine if a stable analog, [Nle(3), D-Phe(6)]-γ2MSH (NDP-γ2MSH), of the native peptide regulated the activity, expression and cellular localization of epithelial sodium channel (ENaC) in a murine inner medullary collecting duct (mIMCD-3) cell line. Our results indicate that expression of the γ2MSH receptor, melanocortin receptor 3 receptor (MC3R), is up-regulated by culturing the cells in media with an increased osmolality (∼400mOsm/kg). Furthermore, stimulation of cAMP signaling and sodium transport by 1nM NDP-γ2MSH occurs only in cells cultured in the high osmolality media. Finally, treatment of mIMCD-3 cells cultured in high osmolality medium for 1h with 1nM NDP-γ2MSH causes a reduction in expression of serum- and glucocorticoid-induced kinase (sgk1) and a reduction in expression and cell surface abundance of the alpha subunit of ENaC. Collectively, this data suggest that γ2MSH directly regulates both ENaC expression and cellular localization in the inner medulla to exert its natriuretic effect., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
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