臨牀消化器内科 Vol.33 No.11(3-4)


特集名 消化器病漢方治療―理論と実践
題名 理論:漢方薬作用機序の科学的解明 (4) 潤腸湯/麻子仁丸
発刊年月 2018年 10月
著者 沼田 朋大 福岡大学医学部生理学講座
著者 井上 隆司 福岡大学医学部生理学講座
【 要旨 】 便秘は日常生活に大きなストレスをもたらす.便秘の症状を緩和するためにいくつかの作用機序の異なる薬物が使用されているが,漢方薬をはじめそれらの分子作用基盤はよく理解されていないことが多い.最近,慢性便秘漢方薬である潤腸湯/麻子仁丸の効果機序が分子生理学的手法を用いた機能解析によって明らかにされた.興味深いことに潤腸湯の投与は,細胞内cAMP上昇によってCFTRチャネルの活性化を介したクロライドイオン流出を誘発し,腸管内への水分泌を促進することが明らかとなった.本稿では,この話題を中心に,類似の作用機序を有し,近年新しい範疇の緩下剤として注目されている小腸刺激性下剤,ルビプロストンについても議論したい.
Theme Kampo Medicine for Gastrointestinal Diseases -- Theory and Practice
Title Novel Mechanism of Kampo Laxatives, Junchoto / Mashiningan
Author Tomohiro Numata Department of Physiology, Fukuoka University School of Medicine
Author Ryuji Inoue Department of Physiology, Fukuoka University School of Medicine
[ Summary ] Several people experience stress in daily life due to constipation. Several drugs that differ mechanistically have been used to mitigate unpleasant symptoms of constipation including Japanese herbal (Kampo) medicines. However, their mechanisms of action are often not well understood. Recently, there has been substantial advancement in this respect of Chinese medicine Junchoto (JCT)/Mashiningan (MNG) empirically prescribed for chronic constipation. In functional analyses at both a cellular and tissue level, JCT/MNG dose-dependently induced channel activities with biophysical and pharmacological features typical of CFTR. Treatment with each adenylate cyclase (AC)-inhibitor, CFTR inhibitor, and siRNA targeting CFTR abolished the JCT-induced channel activity, suggesting that JCT-induced elevated intracellular cAMP causes CFTR activation. Blockade of CFTR activity by the CFTR inhibitor, siRNA-knockdown of CFTR, or application of AC-inhibitor markedly reduced the degree of cell-volume decrease induced by JCT. Moreover, JCT induced Cl-efflux through the CFTR channel to promote water secretion, possibly through increased cAMP production. In this report, we discuss the action mechanisms of lubiprostone, which has recently attracted growing attention as a small intestinal irritant laxative with comparable effect to that of JCT.
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