Regulation of the pacemaker activities in cultured interstitial cells of Cajal by Citrus unshiu peel extracts

Shim,Ji  Hwan; Lee,Soo  Jin; Gim,Huijin; Kim,Hyun  Jung; Han,Taewon; Kim,Jae  Goo; Lim,Eun  Yeong; Kim,Yun  Tai; Kim,Byung  Joo

doi:10.3892/mmr.2016.5689

Regulation of the pacemaker activities in cultured interstitial cells of Cajal by Citrus unshiu peel extracts

Authors:
- Ji Hwan Shim
- Soo Jin Lee
- Huijin Gim
- Hyun Jung Kim
- Taewon Han
- Jae Goo Kim
- Eun Yeong Lim
- Yun Tai Kim
- Byung Joo Kim
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Affiliations: Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnamdo 50612, Republic of Korea, Research Group of Innovative Special Food, Korea Food Research Institute, Seongnam, Gyeonggi 13539, Republic of Korea
Published online on: August 30, 2016 https://doi.org/10.3892/mmr.2016.5689
Pages: 3908-3916

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Abstract

The Citrus unshiu peel has been widely used for the treatment of gastrointestinal (GI) disorders in Eastern traditional medicine. The present study aimed to investigate the effects of Citrus unshiu peel extract (CPE) on the pacemaker activity of the GI tract in cultured interstitial cells of Cajal (ICCs) derived from the mouse small intestine. The whole‑cell patch‑clamp configuration was used to record pacemaker potentials. In current clamp mode, exposure to CPE caused membrane pacemaker depolarization in a concentration‑dependent manner. In the presence of the muscarinic M2 receptor antagonist, methoctramine, CPE induced membrane pacemaker depolarization, whereas treatment with the muscarinic M3 receptor antagonist, 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide, inhibited CPE‑induced responses. When the pipette solution contained guanosine 5'-(β-thio) diphosphate trilithium salt (1 mM), CPE marginally induced membrane pacemaker depolarization. In addition, CPE‑induced membrane pacemaker depolarization was inhibited following exposure to the active phospholipase C (PLC) inhibitor U‑73122, but not the inactive PLC inhibitor U‑73343. In the presence of a p42/p44 mitogen‑activated protein kinase (MAPK) inhibitor (PD98059), a p38 MAPK inhibitor (SB203580) or a c‑jun NH2‑terminal kinase (JNK) II inhibitor, CPE failed to induce membrane pacemaker depolarization. These results suggest that CPE may affect GI motility through modulating ICC pacemaker activity by activating the muscarinic M3 receptor and inducing the G‑protein dependent PLC and MAPK signaling pathways.

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