title: Depolarizing Effects of Daikenchuto on Interstitial Cells of Cajal from Mouse Small Intestine.
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.
  
  
  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-HT3receptor antagonist) or SB269970 (a 5-HT7receptor antagonist) did not block DKT-induced PP depolarization, but RS39604 (a 5-HT4receptor antagonist) did. Methoctramine (a muscarinic M2receptor antagonist) failed to block DKT-induced PP depolarization, but pretreating 4-diphenylacetoxy-N-methylpiperidine methiodide (a muscarinic M3receptor 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. FurthermoreGinsengradix andZingiberisrhizomes depolarized PPs, whereas Zanthoxyli fructus fruit (the third component of DKT) hyperpolarized PPs.
  
  
  CONCLUSIONS
  These results suggest that DKT depolarizes ICC PPs in an internal or external Ca2+-dependent manner by stimulating 5-HT4and M3receptors. Furthermore, the authors suspect that the component in DKT largely responsible for depolarization is probably also a component ofGinsengradix andZingiberisrhizomes.
  
  
  CONCLUSIONS
  Daikenchuto (DKT) depolarized and concentration-dependently decreased the amplitudes of pacemaker potentials (PPs)Y25130 (a 5-HT3receptor antagonist) or SB269970 (a 5-HT7receptor antagonist) did not block DKT-induced PP depolarization, but RS39604 (a 5-HT4receptor antagonist) didMethoctramine (a muscarinic M2receptor antagonist) failed to block DKT-induced PP depolarization, but pretreating 4-DAMP (a muscarinic M3receptor 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.
authors.affiliation: Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do 50612, Republic of Korea.
authors.forename: Hyungwoo
authors.initials: H
authors.lastname: Kim
authors.affiliation: Division of Longevity and Biofunctional Medicine and Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do 50612, Republic of Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Physiology, College of Medicine, Gachon University, Incheon, Republic of Korea.
authors.forename: Dongki
authors.initials: D
authors.lastname: Yang
authors.affiliation: Division of Longevity and Biofunctional Medicine and Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do 50612, Republic of Korea.
authors.forename: Myeong Ho
authors.initials: MH
authors.lastname: Jung
authors.affiliation: Division of Longevity and Biofunctional Medicine and Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do 50612, Republic of Korea.
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Kim
keywords: Daikenchuto; gastrointestinal tract; interstitial cells of Cajal; pacemaker potentials