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Depolarizing Effects of Daikenchuto on Interstitial Cells of Cajal from Mouse Small Intestine
- Source :
- Pharmacognosy Magazine
- Publication Year :
- 2017
-
Abstract
- Background: Daikenchuto (DKT; TJ-100, TU-100), a traditional herbal medicineis used in modern medicine to treat gastrointestinal (GI) functional disorders. Interstitial cells of Cajal (ICCs) are the pacemaker cells of the GI tract and play important roles in the regulation of GI motility. Objective: The objective of this study was to investigate the effects of DKT on the pacemaker potentials (PPs) of cultured ICCs from murine small intestine. Materials and Methods: Enzymatic digestions were used to dissociate ICCs from mouse small intestine tissues. All experiments on ICCs were performed after 12 h of culture. The whole-cell patch-clamp configuration was used to record ICC PPs (current clamp mode). All experiments were performed at 30-32°C. Results: In current-clamp modeDKT depolarized and concentration-dependently decreased the amplitudes of PPs. Y25130 (a 5-HT3 receptor antagonist) or SB269970 (a 5-HT7 receptor antagonist) did not block DKT-induced PP depolarization, but RS39604 (a 5-HT4 receptor antagonist) did. Methoctramine (a muscarinic M2 receptor antagonist) failed to block DKT-induced PP depolarization, but pretreating 4-diphenylacetoxy-N-methylpiperidine methiodide (a muscarinic M3 receptor antagonist) facilitated blockade of DKT-induced PP depolarization. Pretreatment with an external Ca2+-free solution or thapsigargin abolished PPsand under these conditions, DKT did not induce PP depolarization. Furthermore Ginseng radix and Zingiberis rhizomes depolarized PPs, whereas Zanthoxyli fructus fruit (the third component of DKT) hyperpolarized PPs. Conclusion: These results suggest that DKT depolarizes ICC PPs in an internal or external Ca2+-dependent manner by stimulating 5-HT4 and M3 receptors. Furthermore, the authors suspect that the component in DKT largely responsible for depolarization is probably also a component of Ginseng radix and Zingiberis rhizomes. SUMMARY Daikenchuto (DKT) depolarized and concentration-dependently decreased the amplitudes of pacemaker potentials (PPs)Y25130 (a 5-HT3 receptor antagonist) or SB269970 (a 5-HT7 receptor antagonist) did not block DKT-induced PP depolarization, but RS39604 (a 5-HT4 receptor antagonist) didMethoctramine (a muscarinic M2 receptor antagonist) failed to block DKT-induced PP depolarization, but pretreating 4-DAMP (a muscarinic M3 receptor antagonist) facilitated blockade of DKT-induced PP depolarizationGinseng radix and Zingiberis rhizomes depolarized PPswhereas Zanthoxyli fructus fruit (the third component of DKT) hyperpolarized PPs. Abbreviation used: DKT: Daikenchuto, GI: Gastrointestinal, ICCs: Interstitial cells of Cajal, PPs: Pacemaker Potentials.
- Subjects :
- 0301 basic medicine
Modern medicine
medicine.medical_specialty
medicine.drug_class
Pharmaceutical Science
interstitial cells of Cajal
Biology
03 medical and health sciences
symbols.namesake
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
Drug Discovery
Muscarinic acetylcholine receptor
medicine
Methoctramine
Muscarinic acetylcholine receptor M3
Depolarization
Muscarinic acetylcholine receptor M2
Receptor antagonist
Interstitial cell of Cajal
030104 developmental biology
Endocrinology
chemistry
030220 oncology & carcinogenesis
symbols
Original Article
gastrointestinal tract
pacemaker potentials
Daikenchuto
Subjects
Details
- ISSN :
- 09731296
- Volume :
- 13
- Issue :
- 49
- Database :
- OpenAIRE
- Journal :
- Pharmacognosy magazine
- Accession number :
- edsair.doi.dedup.....11e2a9f9d90df98eb8d6fc7c9833ff9f