Kim Hyungwoo, Kim Hyun Jung, Yang Dongki, Jung Myeong Ho, Kim Byung Joo
Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do 50612, Republic of Korea.
Division of Longevity and Biofunctional Medicine and Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do 50612, Republic of Korea.
Pharmacogn Mag. 2017 Jan-Mar;13(49):141-147. doi: 10.4103/0973-1296.196312.
Daikenchuto (DKT; TJ-100, TU-100), a traditional herbal medicineis used in modern medicine to treat gastrointestinal (GI) functional disorders. Interstitial cells of Cajal (ICCs) are the pacemaker cells of the GI tract and play important roles in the regulation of GI motility.
The objective of this study was to investigate the effects of DKT on the pacemaker potentials (PPs) of cultured ICCs from murine small intestine.
Enzymatic digestions were used to dissociate ICCs from mouse small intestine tissues. All experiments on ICCs were performed after 12 h of culture. The whole-cell patch-clamp configuration was used to record ICC PPs (current clamp mode). All experiments were performed at 30-32°C.
In current-clamp modeDKT depolarized and concentration-dependently decreased the amplitudes of PPs. Y25130 (a 5-HT receptor antagonist) or SB269970 (a 5-HT receptor antagonist) did not block DKT-induced PP depolarization, but RS39604 (a 5-HT receptor antagonist) did. Methoctramine (a muscarinic M receptor antagonist) failed to block DKT-induced PP depolarization, but pretreating 4-diphenylacetoxy-N-methylpiperidine methiodide (a muscarinic M receptor antagonist) facilitated blockade of DKT-induced PP depolarization. Pretreatment with an external Ca-free solution or thapsigargin abolished PPsand under these conditions, DKT did not induce PP depolarization. Furthermore radix and rhizomes depolarized PPs, whereas Zanthoxyli fructus fruit (the third component of DKT) hyperpolarized PPs.
These results suggest that DKT depolarizes ICC PPs in an internal or external Ca-dependent manner by stimulating 5-HT and M receptors. Furthermore, the authors suspect that the component in DKT largely responsible for depolarization is probably also a component of radix and rhizomes.
Daikenchuto (DKT) depolarized and concentration-dependently decreased the amplitudes of pacemaker potentials (PPs)Y25130 (a 5-HT receptor antagonist) or SB269970 (a 5-HT receptor antagonist) did not block DKT-induced PP depolarization, but RS39604 (a 5-HT receptor antagonist) didMethoctramine (a muscarinic M receptor antagonist) failed to block DKT-induced PP depolarization, but pretreating 4-DAMP (a muscarinic M receptor antagonist) facilitated blockade of DKT-induced PP depolarizationGinseng radix and Zingiberis rhizomes depolarized PPswhereas Zanthoxyli fructus fruit (the third component of DKT) hyperpolarized PPs. DKT: Daikenchuto, GI: Gastrointestinal, ICCs: Interstitial cells of Cajal, PPs: Pacemaker Potentials.
大建中汤（DKT；TJ - 100，TU - 100），一种传统草药，在现代医学中用于治疗胃肠道（GI）功能紊乱。 Cajal间质细胞（ICCs）是胃肠道的起搏细胞，在胃肠动力调节中起重要作用。
本研究的目的是探讨大建中汤对从小鼠小肠分离培养的ICCs起搏电位（PPs）的影响。
采用酶消化法从小鼠小肠组织中分离ICCs。所有关于ICCs的实验均在培养12小时后进行。采用全细胞膜片钳配置记录ICCs的PPs（电流钳模式）。所有实验均在30 - 32°C下进行。
在电流钳模式下，大建中汤使PPs去极化并呈浓度依赖性降低其幅度。Y25130（一种5 - HT受体拮抗剂）或SB269970（一种5 - HT受体拮抗剂）不能阻断大建中汤诱导的PPs去极化，但RS39604（一种5 - HT受体拮抗剂）可以。甲溴东莨菪碱（一种毒蕈碱M受体拮抗剂）未能阻断大建中汤诱导的PPs去极化，但预先使用4 - 二苯基乙酰氧基 - N - 甲基哌啶甲基碘化物（一种毒蕈碱M受体拮抗剂）可促进对大建中汤诱导的PPs去极化的阻断。用无钙外部溶液或毒胡萝卜素预处理可消除PPs，在这些条件下，大建中汤不会诱导PPs去极化。此外，人参根和干姜使PPs去极化，而花椒果实（大建中汤的第三成分）使PPs超极化。
这些结果表明，大建中汤通过刺激5 - HT和M受体以细胞内或细胞外钙依赖的方式使ICCs的PPs去极化。此外，作者怀疑大建中汤中主要负责去极化的成分可能也是人参根和干姜的一种成分。
大建中汤（DKT）使起搏电位（PPs）去极化并呈浓度依赖性降低其幅度；Y25130（一种5 - HT受体拮抗剂）或SB269970（一种5 - HT受体拮抗剂）不能阻断大建中汤诱导的PPs去极化，但RS39604（一种5- HT受体拮抗剂）可以；甲溴东莨菪碱（一种毒蕈碱M受体拮抗剂）未能阻断大建中汤诱导的PPs去极化，但预先使用4 - DAMP（一种毒蕈碱M受体拮抗剂）可促进对大建中汤诱导的PPs去极化的阻断；人参根和干姜使PPs去极化，而花椒果实（大建中汤的第三成分）使PPs超极化。DKT：大建中汤，GI：胃肠道，ICCs：Cajal间质细胞，PPs：起搏电位 。
