Gamma-melanocyte stimulating hormone regulates the expression and cellular localization of epithelial sodium channel in inner medullary collecting duct cells

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• 作者：Georgina Cope ; Gaurav Kaushik ; Siobhan M. O'Sullivan ; Vincent Healy
• 关键词：Kidney ; Sodium chloride ; Gamma-MSH ; Natriuresis ; Blood pressure ; Cell culture
• 刊名：Peptides
• 出版年：2013
• 出版时间：September, 2013
• 年：2013
• 卷：47
• 期：Complete
• 页码：54-59
• 全文大小：995 K

文摘

Gamma₂-melanocyte-stimulating hormone (¦Ã₂MSH) 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, [Nle³, D-Phe⁶]-¦Ã₂MSH (NDP-¦Ã₂MSH), 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 ¦Ã₂MSH receptor, melanocortin receptor 3 receptor (MC3R), is up-regulated by culturing the cells in media with an increased osmolality (¡«400 mOsm/kg). Furthermore, stimulation of cAMP signaling and sodium transport by 1 nM NDP-¦Ã₂MSH occurs only in cells cultured in the high osmolality media. Finally, treatment of mIMCD-3 cells cultured in high osmolality medium for 1 h with 1 nM NDP-¦Ã₂MSH 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 ¦Ã₂MSH directly regulates both ENaC expression and cellular localization in the inner medulla to exert its natriuretic effect.