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    Depolarizing Effects of Daikenchuto on Interstitial Cells of Cajal from Mouse Small Intestine

    Hyungwoo Kim1, Hyun Jung Kim2, Dongki Yang3, Myeong Ho Jung2, Byung Joo Kim2★★ Corresponding author

    1. 1Division of Pharmacology, School of Korean Medicine, Pusan National University.
    2. 2Division of Longevity and Biofunctional Medicine and Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam‑do 50612.
    3. 3Department of Physiology, College of Medicine, Gachon University, Incheon, Republic of Korea.

    CORRESPONDENCE

    Byung Joo Kim

    Division of Longevity and Biofunctional Medicine and Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam‑do 50612.

    vision@pusan.ac.kr

    Received: 15-12-2015; Revised: 21-01-2016.

    Volume 13, Issue 49 · pp. 141–147 · PUBLISHED 6 January 2017 · DOI: 10.4103/0973-1296.196312

    View on Pharmacogn. Mag. original site ↗

    ABSTRACT

    Background: Daikenchuto (DKT; TJ‑100, TU‑100), a traditional herbal medicine, is 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 mode, DKT 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 PPs, and 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.

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      Kim, H., Kim, H. J., Yang, D., Jung, M. H., & Kim, B. J. (2017). Depolarizing Effects of Daikenchuto on Interstitial Cells of Cajal from Mouse Small Intestine. Pharmacognosy Magazine, 13(49), 141–147. https://doi.org/10.4103/0973-1296.196312