首页> 外文期刊>American Journal of Physiology >Human duodenal mucosal brush border Na(+)/H(+) exchangers NHE2 and NHE3 alter net bicarbonate movement.
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Human duodenal mucosal brush border Na(+)/H(+) exchangers NHE2 and NHE3 alter net bicarbonate movement.

机译:人十二指肠粘膜刷边界Na(+)/ H(+)交换器NHE2和NHE3改变净碳酸氢盐运动。

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摘要

The proximal duodenal mucosa secretes HCO that serves to protect the epithelium from injury. In isolated human duodenal enterocytes in vitro, multiple luminal membrane proteins are involved in acid/base transport. We postulated that one or more isoforms of the Na(+)/H(+) exchanger (NHE) family is located on the apical surface of human duodenal mucosal epithelial cells and thereby contributes to duodenal mucosal HCO transport. Duodenal biopsies were obtained from human volunteers, and the presence of NHE2 and NHE3 was determined by using previously characterized polyclonal antibodies (Ab 597 for NHE2 and Ab 1381 for NHE3). In addition, proximal duodenal mucosal HCO(3)(-) transport was measured in humans in vivo in response to luminal perfusion of graded doses of amiloride; 10(-5)--10(-4) M amiloride was used to inhibit NHE2 and 10(-3) M amiloride to inhibit NHE3. Both NHE2 and NHE3 were localized principally to the brush border of duodenal villus cells. Sequential doses of amiloride resulted in significant, step-wise increases in net duodenal HCO(3)(-) output. Inhibition of NHE2 with 10(-5) M and 10(-4) M amiloride significantly increased net HCO(3)(-) output. Moreover, there was an additional, equivalent increase (P < 0.05) in duodenal HCO(3)(-) output with 10(-3) M amiloride, which inhibited NHE3. We conclude that 1) NHE2 and NHE3 are localized principally to the brush border of human duodenal villus epithelial cells; 2) sequential inhibition of NHE2 and NHE3 isoforms resulted in step-wise increases in net HCO(3)(-) output; 3) NHE2 and NHE3 participate in human duodenal villus cell HCO(3)(-) transport; and 4) the contribution of NHE-related transport events should be considered when studying duodenal HCO(3)(-) transport processes.
机译:十二指肠近端粘膜分泌HCO,可保护上皮不受损伤。在体外分离的人十二指肠肠上皮细胞中,多种腔膜蛋白参与酸/碱转运。我们假定Na(+)/ H(+)交换器(NHE)家族的一种或多种同工型位于人十二指肠粘膜上皮细胞的顶表面,从而有助于十二指肠粘膜HCO的运输。十二指肠活检取自人类志愿者,通过使用先前鉴定的多克隆抗体(NHE2为Ab 597,NHE3为Ab 1381)来确定NHE2和NHE3的存在。此外,响应于腔内灌注分级剂量的阿米洛利,在体内测量了十二指肠近端HCO(3)(-)转运。 10(-5)-10(-4)M阿米洛利用于抑制NHE2,10(-3)M阿米洛利用于抑制NHE3。 NHE2和NHE3都主要定位在十二指肠绒毛细胞的刷状缘。连续剂量的阿米洛利导致十二指肠HCO(3)(-)净输出量显着逐步增加。用10(-5)M和10(-4)M阿米洛利抑制NHE2会显着增加净HCO(3)(-)的产量。此外,在十二指肠HCO(3)(-)的输出中,有10(-3)M阿米洛利产生了额外的等效增加(P <0.05),这会抑制NHE3。我们得出以下结论:1)NHE2和NHE3主要位于人十二指肠绒毛上皮细胞的刷状缘; 2)NHE2和NHE3亚型的顺序抑制导致净HCO(3)(-)输出的逐步增加; 3)NHE2和NHE3参与人十二指肠绒毛细胞HCO(3)(-)的运输; 4)在研究十二指肠HCO(3)(-)的转运过程时,应考虑NHE相关转运事件的贡献。

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