Brief Article
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World J Gastroenterol. Apr 14, 2013; 19(14): 2249-2255
Published online Apr 14, 2013. doi: 10.3748/wjg.v19.i14.2249
Effects of Lizhong Tang on cultured mouse small intestine interstitial cells of Cajal
Min Woo Hwang, Jung Nam Kim, Ho Jun Song, Bora Lim, Young Kyu Kwon, Byung Joo Kim
Min Woo Hwang, Department of Sasang Constitutional Medicine, College of Korean Medicine, Kyung-hee University, Seoul 130-701, South Korea
Jung Nam Kim, Ho Jun Song, Bora Lim, Young Kyu Kwon, Byung Joo Kim, School of Korean Medicine, Pusan National University, Yangsan 626-870, South Korea
Author contributions: Kwon YK and Kim BJ designed the research; Hwang MW, Kim JN and Song HJ performed the experiments; Lim B, Kwon YK and Kim BJ analyzed the data; and Hwang MW and Kim BJ wrote the paper.
Supported by The Traditonal Korean Medicine R and D Project, Ministry of Health and Welfare, South Korea, No. B120008
Correspondence to: Byung Joo Kim, PhD, School of Korean Medicine, Pusan National University, Beomeori, Mulgeum-eup, Yangsan 626-870, South Korea. vision@pusan.ac.kr
Telephone: +82-51-5108469 Fax: +82-51-5108420
Received: November 12, 2012
Revised: February 6, 2013
Accepted: February 8, 2013
Published online: April 14, 2013
Abstract

AIM: To investigate the effects of Lizhong Tang, an herbal product used in traditional Chinese medicine, on mouse small intestine interstitial cells of Cajal (ICCs).

METHODS: Enzymatic digestions were used to dissociate ICCs from mouse small intestine tissues. The ICCs were morphologically distinct from other cell types in culture and were identified using phase contrast microscopy after verification with anti c-kit antibody. A whole-cell patch-clamp configuration was used to record potentials (current clamp) from cultured ICCs. All of the experiments were performed at 30-32  °C.

RESULTS: ICCs generated pacemaker potentials, and Lizhong Tang produced membrane depolarization in current-clamp mode. The application of flufenamic acid (a nonselective cation channel blocker) abolished the generation of pacemaker potentials by Lizhong Tang. Pretreatment with thapsigargin (a Ca2+-ATPase inhibitor in the endoplasmic reticulum) also abolished the generation of pacemaker potentials by Lizhong Tang. However, pacemaker potentials were completely abolished in the presence of an external Ca2+-free solution, and under this condition, Lizhong Tang induced membrane depolarizations. Furthermore, When GDP-β-S (1 mmol/L) was in the pipette solution, Lizhong Tang still induced membrane depolarizations. In addition, membrane depolarizations were not inhibited by chelerythrine or calphostin C, which are protein kinase C inhibitors, but were inhibited by U-73122, an active phospholipase C inhibitors.

CONCLUSION: These results suggest that Lizhong Tang might affect gastrointestinal motility by modulating pacemaker activity in interstitial cells of Cajal.

Keywords: Interstitial cells of Cajal, Lizhong Tang, Motility, Gastrointestinal tract, Whole-cell patch clamp configuration

Core tip: The gastroprokinetic effects of Lizhong Tang are mediated by the induction of pacemaker potentials in interstitial cells of Cajal (ICCs). Taken together, our data suggest that the gastroprokinetic effects of Lizhong Tang are mediated by the induction of pacemaker potentials in ICCs. Considering the effects of this drug on ICCs, further research is required to identify the compounds responsible for the effects of Lizhong Tang and to determine their mechanisms of action.