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Tytuł:
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Rikkunshito Depolarizes Pacemaker Potentials of Cultured Interstitial Cells of Cajal through Ghrelin Receptors in Murine Small Intestine.
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Autorzy:
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Kim JN; Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan, Republic of Korea.
Nam JH; Department of Physiology, College of Medicine, Dongguk University, Kyungju, Republic of Korea.
Lee JR; Department of Pharmaceutical Engineering, Daegu Haany University, Gyeongsan, Republic of Korea.
Kim SC; College of Oriental Medicine, Daegu Haany University, Gyeongsan, Republic of Korea.
Kwon YK; Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan, Republic of Korea.
Kim BJ; Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan, Republic of Korea, .
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Źródło:
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Digestion [Digestion] 2020; Vol. 101 (3), pp. 227-238. Date of Electronic Publication: 2019 Mar 19.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Original Publication: Basel, Karger.
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MeSH Terms:
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Drugs, Chinese Herbal/*pharmacology
Gastrointestinal Motility/*drug effects
Interstitial Cells of Cajal/*drug effects
Membrane Potentials/*drug effects
Receptors, Ghrelin/*metabolism
Animals ; Cells, Cultured ; Dose-Response Relationship, Drug ; Gastrointestinal Motility/physiology ; Interstitial Cells of Cajal/physiology ; Intestine, Small/cytology ; Intestine, Small/physiology ; Mice ; Patch-Clamp Techniques ; Primary Cell Culture ; Signal Transduction/drug effects
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Contributed Indexing:
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Keywords: Gastrointestinal tract; Interstitial cells of Cajal; Motility; Pacemaker potentials ; Rikkunshito
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Substance Nomenclature:
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0 (Drugs, Chinese Herbal)
0 (Receptors, Ghrelin)
0 (liu-jun-zi-tang)
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Entry Date(s):
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Date Created: 20190320 Date Completed: 20210301 Latest Revision: 20210301
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Update Code:
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20240105
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DOI:
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10.1159/000498986
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PMID:
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30889598
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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.
(© 2019 S. Karger AG, Basel.)
