In:
Digestion, S. Karger AG, Vol. 101, No. 3 ( 2020), p. 227-238
Abstract:
〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 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. 〈 sup 〉 〈 /sup 〉 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 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. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 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 Ca 〈 sup 〉 2+ 〈 /sup 〉 -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 Ca 〈 sup 〉 2+ 〈 /sup 〉 -activated Cl 〈 sup 〉 – 〈 /sup 〉 channels (ANO1) currents. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Rikkunshito depolarized pacemaker potentials of ICCs via ghrelin receptor and G protein through internal or external Ca 〈 sup 〉 2+ 〈 /sup 〉 -, 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.
Type of Medium:
Online Resource
ISSN:
0012-2823
,
1421-9867
Language:
English
Publisher:
S. Karger AG
Publication Date:
2020
detail.hit.zdb_id:
1482218-0
