Epithelial Na+ channel delta subunit is an acid sensor in the human oesophagus.
Epithelial Na+ channel delta subunit is an acid sensor in the human oesophagus.
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上皮钠通道δ亚基是人类食道中的酸传感器。
DOI：
10.1016/j.ejphar.2008.10.022
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发表时间：
2008
影响因子：
5
通讯作者：
S. Shimada
中科院分区：
文献类型：
--
作者：
H. Yamamura;S. Ugawa;T. Ueda;M. Nagao;T. Joh;S. Shimada
胃食管反流病是由于胃内容物反流到食管，导致食管管腔受到胃酸损害而引起的。参与食管上皮防御的酸传感器仍不清楚。最近，我们描述了上皮Na+通道δ亚基（ENaCδ）是人脑pH传感器的候选分子。在这里，利用逆转录聚合酶链反应和原位杂交方法，我们发现质子敏感的ENaCδ在人类食管上皮层中强烈表达，这是可以暴露于酸性环境的代表性外周组织。其他 ENaC 亚基（α、β 和 γ）也位于此处。根据表达模式，在非洲爪蟾卵母细胞表达系统中模拟人食管 ENaC 复合物，并使用两电极电压钳技术记录对酸性 pH 值的反应。模仿人类食管的 ENaCδβγα 复合物在 -60 mV 的保持电位下产生阿米洛利敏感的内向电流。 ENaCδβγα电流被酸性pH（pH 4.0）显着激活，大约等于胃酸反流到食道时的管腔值。总之，ENaCδ 是人类胃肠系统 pH 传感的候选分子，为胃食管反流病提供了新的治疗靶点。
Gastro-oesophageal reflux disease is caused by the reflux of gastric contents into the oesophagus, and thus the oesophageal lumen is damaged by gastric acid. The acid sensor involved in oesophageal epithelial defense is still unclear. Recently, we described that the epithelial Na+channel δ subunit (ENaCδ) is a candidate molecule for a pH sensor in the human brain. Here, using reverse transcription-polymerase chain reaction and in situ hybridization methods, we showed that the proton-sensitive ENaCδ was strongly expressed in the epithelial layer of the human oesophagus, representative peripheral tissue that can be exposed to an acidic environment. Other ENaC subunits (α, β, and γ) were also localized there. Based on the expression pattern, human oesophageal ENaC complex was mimicked in the Xenopus oocyte expression system and the response to acidic pH was recorded using a two-electrode voltage-clamp technique. The human oesophageal-mimicking ENaCδβγα complex generated an amiloride-sensitive inward current at the holding potential of −60 mV. The ENaCδβγα current was significantly activated by acidic pH (pH 4.0), approximately equal to the luminal value when gastric acid refluxes into the oesophagus. In conclusion, ENaCδ is a candidate molecule for pH sensing in the gastrointestinal system in humans, providing a novel therapeutic target for gastro-oesophageal reflux disease.
DOI：
10.1046/j.1523-1747.1999.00742.x
发表时间：
1999
期刊：
The Journal of investigative dermatology.
影响因子：
--
作者：
Oda,Y;Imanzahrai,A;Kwong,A;Komuves,L;Elias,PM;Largman,C;Mauro,T
通讯作者：
Mauro,T
影响因子：
6.5
作者：
Mauro, T;Guitard, M;Hummler, E
通讯作者：
Hummler, E
大鼠结肠和肺上皮钠通道亚基 mRNA 表达的发育调节。
DOI：
10.1152/ajpgi.1998.275.6.g1227
发表时间：
1998
期刊：
The American journal of physiology
影响因子：
--
作者：
Watanabe,S;Matsushita,K;Stokes,JB;McCrayJr,PB
通讯作者：
McCrayJr,PB