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Epithelial Na+ channel delta subunit mediates acid-induced ATP release in the human skin
Authors:Yamamura Hisao  Ugawa Shinya  Ueda Takashi  Nagao Masataka  Shimada Shoichi
Affiliation:a Department of Molecular Morphology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi Mizuhocho Mizuhoku, Nagoya 467-8601, Japan
b Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan
c Department of Forensic Medical Science, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan
Abstract:The amiloride-sensitive epithelial Na+ channel (ENaC) regulates Na+ homeostasis in cells and across epithelia. Although we described that ENaCδ is a candidate molecule for a pH sensor in the human brain, the physiological and pathological roles of ENaCδ in non-neuronal tissues are still unknown. Here we show a novel physiological function of ENaCδ in peripheral tissues in humans. Expression analyses at the level of mRNA clearly revealed that ENaCδ was abundantly expressed in human epidermis and keratinocytes. In addition, ENaCδ protein was detected in there. In cultured keratinocytes, acidic stress (pH 5.0) evoked ATP release, which was significantly reduced in the presence of 100 μM amiloride or 10 μM benzamil. In conclusion, ENaCδ may be involved in the mechanism underlying pH sensing followed by the regulation of cell viability in the human skin.
Keywords:Epithelial Na+ channel   δ subunit   Skin   Keratinocyte   ATP   pH   Amiloride
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