Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2017; 23(29): 5313-5323
Published online Aug 7, 2017. doi: 10.3748/wjg.v23.i29.5313
Hwangryunhaedok-tang induces the depolarization of pacemaker potentials through 5-HT3 and 5-HT4 receptors in cultured murine small intestine interstitial cells of Cajal
Hyun Jung Kim, Guem San Lee, Hyungwoo Kim, Byung Joo Kim
Hyun Jung Kim, Byung Joo Kim, Division of Longevity and Biofunctional Medicine, Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan 50612, South Korea
Guem San Lee, Wonkwang University College of Korean Medicine, Iksan 54538, South Korea
Hyungwoo Kim, Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan 50612, South Korea
Byung Joo Kim, Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Gyeongsangnamdo 50612, South Korea
Author contributions: Kim HJ and Kim BJ designed the research; Kim HJ, Lee GS and Kim H performed the experiments; Kim HJ and Kim BJ analyzed the data; and Kim HJ and Kim BJ wrote the paper.
Supported by the National Research Foundation of Korea Grant funded by the Korea Government (MSIP), No. 2014R1A5A2009936.
Institutional animal care and use committee statement: The animal care and experiments in accordance with the guidelines issued by the Institutional Animal Care and Use Committee at Pusan National University (Busan, Republic of Korea; Approval No. PNU-2015-1036).
Conflict-of-interest statement: The authors have no disclosures to report.
Data sharing statement: No additional are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Byung Joo Kim, PhD, Associate Professor, Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Beomeori, Mulgeum-eup, Yangsan, Gyeongsangnamdo 50612, South Korea. vision@pusan.ac.kr
Telephone: +82-51-5108469 Fax: +82-51-5108420
Received: March 2, 2017
Peer-review started: March 4, 2017
First decision: April 6, 2017
Revised: April 18, 2017
Accepted: June 9, 2017
Article in press: June 12, 2017
Published online: August 7, 2017
Abstract
AIM

To investigate the effects of a water extract of Hwangryunhaedok-tang (HHTE) on the pacemaker potentials of mouse interstitial cells of Cajal (ICCs).

METHODS

We dissociated ICCs from small intestines and cultured. ICCs were immunologically identified using an anti-c-kit antibody. We used the whole-cell patch-clamp configuration to record the pacemaker potentials generated by cultured ICCs under the current clamp mode (I = 0). All experiments were performed at 30 °C-32 °C

RESULTS

HHTE dose-dependently depolarized ICC pacemaker potentials. Pretreatment with a 5-HT3 receptor antagonist (Y25130) or a 5-HT4 receptor antagonist (RS39604) blocked HHTE-induced pacemaker potential depolarizations, whereas pretreatment with a 5-HT7 receptor antagonist (SB269970) did not. Intracellular GDPβS inhibited HHTE-induced pacemaker potential depolarization and pretreatment with a Ca2+-free solution or thapsigargin abolished the pacemaker potentials. In the presence of a Ca2+-free solution or thapsigargin, HHTE did not depolarize ICC pacemaker potentials. In addition, HHTE-induced pacemaker potential depolarization was unaffected by a PKC inhibitor (calphostin C) or a Rho kinase inhibitor (Y27632). Of the four ingredients of HHT, Coptidis Rhizoma and Gardeniae Fructus more effectively inhibited pacemaker potential depolarization.

CONCLUSION

These results suggest that HHTE dose-dependently depolarizes ICC pacemaker potentials through 5-HT3 and 5-HT4 receptors via external and internal Ca2+ regulation and via G protein-, PKC- and Rho kinase-independent pathways.

Keywords: Hwangryunhaedok-tang, Interstitial cells of Cajal, Pacemaker potentials, Gastrointestinal tract, Motility

Core tip: Hwangryunhaedok-tang, a traditional herbal medicine, has been used to treat gastrointestinal diseases. Our data suggest that HHT can depolarize the pacemaker potentials of cultured interstitial cells of Cajal from mouse small intestine and may be a novel prokinetic agent.