Gamma-melanocyte stimulating hormone regulates the expression and cellular localization of epithelial sodium channel in inner medullary collecting duct cells |
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Institution: | 1. Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH;2. Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX;3. Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium;4. Hasselt University, Diepenbeek, Belgium;1. Cardiovascular Division, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States;2. Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States;3. Cardiovascular Division, Department of Medicine, University of Texas Southwestern, Dallas, TX, United States |
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Abstract: | Gamma2-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, Nle3, D-Phe6]-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 (∼400 mOsm/kg). Furthermore, stimulation of cAMP signaling and sodium transport by 1 nM NDP-γ2MSH 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-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. |
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Keywords: | Kidney Sodium chloride Gamma-MSH Natriuresis Blood pressure Cell culture |
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