title: Gamma-melanocyte stimulating hormone regulates the expression and cellular localization of epithelial sodium channel in inner medullary collecting duct cells.
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.
authors.affiliation: Department of Physiology, University College Cork, Ireland.
authors.forename: Georgina
authors.initials: G
authors.lastname: Cope
authors.forename: Gaurav
authors.initials: G
authors.lastname: Kaushik
authors.forename: Siobhan M
authors.initials: SM
authors.lastname: O'Sullivan
authors.forename: Vincent
authors.initials: V
authors.lastname: Healy
mesh_terms: D000818:Animals; D002460:Cell Line; D003470:Culture Media; D000242:Cyclic AMP / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D017136:Ion Transport; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009318:Natriuresis / Q000235:genetics; D009994:Osmolar Concentration; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D044104:Receptor, Melanocortin, Type 3 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000494:pharmacology; D019825:gamma-MSH / Q000235:genetics* / Q000378:metabolism; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D003470:Culture Media; D000242:Cyclic AMP; D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D044104:Receptor, Melanocortin, Type 3; D012964:Sodium; D000521:alpha-MSH; D019825:gamma-MSH; D000099184:Serum-Glucocorticoid Regulated Kinases; C470053:Mc3r protein, mouse; C027756:MSH, 4-Nle-7-Phe-alpha-
keywords: Blood pressure; Cell culture; Gamma-MSH; Kidney; Natriuresis; Sodium chloride