title: Regulation of the pacemaker activities in cultured interstitial cells of Cajal by Citrus unshiu peel extracts.
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.
authors: Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnamdo 50612, Republic of Korea.
authors: Ji Hwan
authors: JH
authors: Shim
authors: Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnamdo 50612, Republic of Korea.
authors: Soo Jin
authors: SJ
authors: Lee
authors: Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnamdo 50612, Republic of Korea.
authors: Huijin
authors: H
authors: Gim
authors: Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnamdo 50612, Republic of Korea.
authors: Hyun Jung
authors: HJ
authors: Kim
authors: Research Group of Innovative Special Food, Korea Food Research Institute, Seongnam, Gyeonggi 13539, Republic of Korea.
authors: Taewon
authors: T
authors: Han
authors: Research Group of Innovative Special Food, Korea Food Research Institute, Seongnam, Gyeonggi 13539, Republic of Korea.
authors: Jae Goo
authors: JG
authors: Kim
authors: Research Group of Innovative Special Food, Korea Food Research Institute, Seongnam, Gyeonggi 13539, Republic of Korea.
authors: Eun Yeong
authors: EY
authors: Lim
authors: Research Group of Innovative Special Food, Korea Food Research Institute, Seongnam, Gyeonggi 13539, Republic of Korea.
authors: Yun Tai
authors: YT
authors: Kim
authors: Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnamdo 50612, Republic of Korea.
authors: Byung Joo
authors: BJ
authors: Kim
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002957:Citrus / Q000737:chemistry*; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects; D056885:Interstitial Cells of Cajal / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018408:Patch-Clamp Techniques; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004365:Drugs, Chinese Herbal; D043587:Receptor, Muscarinic M3; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins