Format

Send to

Choose Destination
Digestion. 2019 Mar 19:1-12. doi: 10.1159/000498986. [Epub ahead of print]

Rikkunshito Depolarizes Pacemaker Potentials of Cultured Interstitial Cells of Cajal through Ghrelin Receptors in Murine Small Intestine.

Author information

1
Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan, Republic of Korea.
2
Department of Physiology, College of Medicine, Dongguk University, Kyungju, Republic of Korea.
3
Department of Pharmaceutical Engineering, Daegu Haany University, Gyeongsan, Republic of Korea.
4
College of Oriental Medicine, Daegu Haany University, Gyeongsan, Republic of Korea.
5
Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan, Republic of Korea, vision@pusan.ac.kr.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

KEYWORDS:

Gastrointestinal tract; Interstitial cells of Cajal; Motility; Pacemaker potentials ; Rikkunshito

PMID:
30889598
DOI:
10.1159/000498986

Supplemental Content

Full text links

Icon for S. Karger AG, Basel, Switzerland
Loading ...
Support Center