Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan, Republic of Korea.
Department of Physiology, College of Medicine, Dongguk University, Kyungju, Republic of Korea.
Digestion. 2020;101(3):227-238. doi: 10.1159/000498986. Epub 2019 Mar 19.
Rikkunshito has been used to treat gastrointestinal (GI) disorders. The purpose of this study was to investigate the effects of Rikkunshito, a traditional Japanese herbal medicine, on the pacemaker potentials of interstitial cells of Cajal (ICCs) from the small intestines of mice.
We isolated ICCs from the small intestines of mice, and the whole-cell patch-clamp configuration was used to record the pacemaker potentials in cultured ICCs and membrane currents.
Rikkunshito depolarized ICC pacemaker potentials in a dose-dependent manner. Pretreatment with GSK1614343 or (D-Lys3)-growth hormone-releasing peptide-6 inhibited Rikkunshito-induced depolarization of pacemaker potentials. Intracellular GDP-β-S inhibited Rikkunshito-induced effects. In Ca2+-free solution or in the presence of thapsigargin, Rikkunshito did not depolarize pacemaker potentials. Moreover, in the presence of U-73122 or xestospongin C, Rikkunshito-induced effects were inhibited. However, in the presence of staurosporine, Go6976 or Rottlerin, Rikkunshito depolarized pacemaker potentials. Furthermore, Rikkunshito inhibited both transient receptor potentials melastatin 7 (TRPM7) and Ca2+-activated Cl- channels (ANO1) currents.
Rikkunshito depolarized pacemaker potentials of ICCs via ghrelin receptor and G protein through internal or external Ca2+-, phospholipase C-, and inositol triphosphate-dependent and protein kinase C-, TRPM7-, and ANO1-independent pathways. The study shows that Rikkunshito may alleviate GI motility disorders through its depolarizing effects on ICCs.
和胃汤已被用于治疗胃肠（GI）疾病。本研究旨在探讨和胃汤（一种传统的日本草药）对从小鼠小肠分离的间质细胞 Cajal（ICC）起搏电位的影响。
我们从小鼠小肠中分离 ICC，并使用全细胞膜片钳记录培养 ICC 中的起搏电位和膜电流。
和胃汤以剂量依赖性方式使 ICC 起搏电位去极化。GSK1614343 或（D-Lys3）-生长激素释放肽-6 的预处理抑制了和胃汤诱导的起搏电位去极化。细胞内 GDP-β-S 抑制了和胃汤诱导的作用。在无钙溶液中或存在 thapsigargin 时，和胃汤不会使起搏电位去极化。此外，在 U-73122 或 xestospongin C 存在下，和胃汤诱导的作用被抑制。然而，在 staurosporine、Go6976 或 Rottlerin 存在下，和胃汤使起搏电位去极化。此外，和胃汤抑制瞬时受体电位 melastatin 7（TRPM7）和 Ca2+-激活 Cl-通道（ANO1）电流。
和胃汤通过生长激素释放肽受体和 G 蛋白通过内或外 Ca2+、磷脂酶 C、三磷酸肌醇依赖性和蛋白激酶 C、TRPM7 和 ANO1 非依赖性途径使 ICC 起搏电位去极化。该研究表明，和胃汤可能通过对 ICC 的去极化作用缓解 GI 运动障碍。
