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去乙酰基比沙可啶诱导大鼠结肠和直肠上皮细胞氯离子分泌

Desacetyl bisacodyl-induced epithelial Cl(-) secretion in rat colon and rectum.

作者信息

Fujita Takuya, Karaki Shin-ichiro, Tateoka Takashi, Kuwahara Atsukazu

机构信息

Laboratory of Physiology, Department of Environmental and Life Sciences/Graduate School of Nutritional and Environmental Sciences, University of Shizuoka.

出版信息

Biomed Res. 2016;37(1):13-20. doi: 10.2220/biomedres.37.13.

Abstract

The purpose of this study was to clarify the mode of desacetyl bisacodyl (DAB)-induced secretory action in intestinal tissues using an Ussing chamber assay. DAB is the active metabolite of the laxative bisacodyl. In mucosal-submucosal preparations, mucosal application of DAB induced a transient decrease followed by subsequent increases in short-circuit current and tissue conductance in a concentration-dependent manner. DAB-induced responses occurred from the middle colon to the rectal segment but not in the proximal colon. Moreover, these responses were not observed under chloride (Cl(-))-free conditions or in the presence of DAB on the serosal side of the mucosalsubmucosal specimens. Treatment with tetrodotoxin had no effect on the DAB-induced responses; however, mucosal treatment with a COX inhibitor piroxicam resulted in the elimination of responses. These results suggest that DAB may contribute to the laxative action by inducing Cl(-) secretion which is associated with the COX signaling pathway. This study also demonstrated that the DAB target molecule is present on the mucosal side from the middle colon to the rectal segment.

摘要

本研究的目的是使用尤斯灌流小室分析法阐明去乙酰比沙可啶(DAB)在肠道组织中诱导分泌作用的模式。DAB是泻药比沙可啶的活性代谢产物。在黏膜-黏膜下层制剂中,黏膜应用DAB会引起短路电流和组织电导先短暂降低,随后以浓度依赖的方式升高。DAB诱导的反应从中结肠到直肠段均可发生,但在近端结肠未出现。此外,在无氯离子(Cl(-))条件下或在黏膜-黏膜下层标本浆膜侧存在DAB时未观察到这些反应。用河豚毒素处理对DAB诱导的反应没有影响;然而,用环氧化酶(COX)抑制剂吡罗昔康进行黏膜处理可消除反应。这些结果表明,DAB可能通过诱导与COX信号通路相关的Cl(-)分泌来促进泻药作用。本研究还表明,DAB靶分子存在于从中结肠到直肠段的黏膜侧。

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