Modulation of Pacemaker Potentials in Murine Small Intestinal Interstitial Cells of Cajal by Gamisoyo-San, a Traditional Chinese Herbal Medicine

作者：Kim Doeun; Kim Jung Nam; Nam Joo Hyun; Lee Jong Rok; Kim Sang Chan; Kim Byung Joo^*

来源：Digestion, 2018, 98(1): 56-68.

DOI：10.1159/000487186

• Gamisoyo-San
• Interstitial cells of Cajal
• Gastrointestinal tract
• Prokinetic agent
• Gastrointestinal motility

Background: The Gamisoyo-san (GSS) has been used for improving the gastrointestinal (GI) symptoms. The purpose of this study was to investigate the effects of GSS, a traditional Chinese herbal medicine, on the pacemaker potentials of mouse small intestinal interstitial cells of Cajal (ICCs). Methods: ICCs from the small intestines were dissociated and cultured. Whole-cell patch-clamp configuration was used to record pacemaker potentials and membrane currents. Results: GSS depolarized ICC pacemaker potentials in a dose-dependent manner. Pretreatment with 4-diphenyl-acetoxypiperidinium iodide completely inhibited GSS-induced pacemaker potential depolarizations. Intracellular GDP-beta-S inhibited GSS-induced effects, and in the presence of U-73122, GSS-induced effects were inhibited. Also, GSS in the presence of a Ca2+-free solution or thapsigargin did not depolarize pacemaker potentials. However, in the presence of calphostin C, GSS slightly depolarized pacemaker potentials. Furthermore, GSS inhibited both transient receptor potential melastatin 7 and Ca2+-activated Cl- channel (anoctamint) currents. Conclusion: GSS depolarized pacemaker potentials of ICCs via G protein and muscarinic M-3 receptor signaling pathways and through internal or external Ca2+-, phospholipase C-, and protein kinase C-dependent and transient receptor potential melastatin 7-, and anoctamin 1-independent pathways. The study shows that GSS may regulate GI tract motility, suggesting that GSS could be a basis for developing novel prokinetic agents for treating GI motility dysfunctions.

• 出版日期2018