Gamma-melanocyte stimulating hormone regulates the expression and cellular localization of epithelial sodium channel in inner medullary collecting duct cells
Gamma-melanocyte stimulating hormone regulates the expression and cellular localization of epithelial sodium channel in inner medullary collecting duct cells
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DOI：
10.1016/j.peptides.2013.07.007
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发表时间：
2013-09-01
期刊：
影响因子：
3
通讯作者：
Healy, Vincent
中科院分区：
文献类型：
--
作者：
Cope, Georgina;Kaushik, Gaurav;Healy, Vincent
γ（2）-促黑素细胞激素（γ 2 MSH）是由脑垂体释放的肽激素，其被认为直接作用于肾内髓质以促进增加的钠排泄到尿中（尿钠排泄）。本研究的目的是确定天然肽的稳定类似物[Nle（3），D-Phe（6）]-γ 2 MSH（NDP-γ 2 MSH）是否调节小鼠内髓集合管（mIMCD-3）细胞系中上皮钠通道（ENaC）的活性、表达和细胞定位。我们的研究结果表明，表达的γ 2 MSH受体，黑皮质素受体3受体（MC 3R），是上调培养中的细胞与增加的渗透压（类似于400 mOsm/kg）。此外，1 nM NDP-γ 2 MSH刺激cAMP信号传导和钠转运仅发生在高渗透压培养基中培养的细胞中。最后，用1 nM NDP-γ 2 MSH处理在高渗透压培养基中培养1小时的mIMCD-3细胞，导致血清和糖皮质激素诱导的激酶（sgkl）的表达减少，以及ENaC α亚基的表达和细胞表面丰度减少。总的来说，这些数据表明，γ-2 MSH直接调节ENaC表达和细胞定位在内髓质发挥其利钠作用。(C)2013 Elsevier Inc. All rights reserved.
Gamma(2)-melanocyte-stimulating hormone (gamma 2MSH) 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)]-gamma 2MSH (NDP-gamma 2MSH), 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 gamma 2MSH receptor, melanocortin receptor 3 receptor (MC3R), is up-regulated by culturing the cells in media with an increased osmolality (similar to 400 mOsm/kg). Furthermore, stimulation of cAMP signaling and sodium transport by 1 nM NDP-gamma 2MSH 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-gamma 2MSH causes a reduction in expression of serum- and glucocorticoid-induced kinase (sgkl) and a reduction in expression and cell surface abundance of the alpha subunit of ENaC. Collectively, this data suggest that gamma 2MSH directly regulates both ENaC expression and cellular localization in the inner medulla to exert its natriuretic effect. (C) 2013 Elsevier Inc. All rights reserved.