Ginsenoside Re inhibits pacemaker potentials via adenosine triphosphate-sensitive potassium channels and the cyclic guanosine monophosphate/nitric oxide-dependent pathway in cultured interstitial cells of Cajal from mouse small intestine

被引:20
作者
Hong, Noo Ri [1 ,2 ]
Park, Hyun Soo [1 ,2 ]
Ahn, Tae Seok [1 ,2 ]
Kim, Hyun Jung [1 ,2 ]
Ha, Ki-Tae [2 ,3 ]
Kim, Byung Joo [1 ,2 ]
机构
[1] Pusan Natl Univ, Sch Korean Med, Div Longev & Biofunct Med, Yangsan 626870, Gyeongsangnamdo, South Korea
[2] Pusan Natl Univ, Sch Korean Med, Healthy Aging Korean Med Res Ctr, Yangsan 626870, Gyeongsangnamdo, South Korea
[3] Pusan Natl Univ, Sch Korean Med, Div Appl Med, Yangsan 626870, Gyeongsangnamdo, South Korea
基金
新加坡国家研究基金会;
关键词
gastrointestinal tract; ginsenoside Re; interstitial cells of Cajal; patch clamp configuration; NITRIC-OXIDE; CURRENTS; CONDUCTANCE; GINTONIN; VACCINE; ARTERY;
D O I
10.1016/j.jgr.2015.02.004
中图分类号
Q94 [植物学];
学科分类号
071001 [植物学];
摘要
Background: Ginseng belongs to the genus Panax. Its main active ingredients are the ginsenosides. Interstitial cells of Cajal (ICCs) are the pacemaker cells of the gastrointestinal (GI) tract. To understand the effects of ginsenoside Re (GRe) on CI motility, the authors investigated its effects on the pacemaker activity of ICCs of the murine small intestine. Methods: Interstitial cells of Cajal were dissociated from mouse small intestines by enzymatic digestion. The whole-cell patch clamp configuration was used to record pacemaker potentials in cultured ICCs. Changes in cyclic guanosine monophosphate (cGMP) content induced by GRe were investigated. Results: Ginsenoside Re (20-40 mu M) decreased the amplitude and frequency of ICC pacemaker activity in a concentration-dependent manner. This action was blocked by guanosine 5'[beta-thio]diphosphate [a guanosine-5'-triphosphate (GTP)-binding protein inhibitor] and by glibenclamide [an adenosine triphosphate (ATP)-sensitive K+ channel blocked. To study the GRe-induced signaling pathway in ICCs, the effects of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (a guanylate cyclase inhibitor) and RP-8-CPT-cGMPS (a protein kinase G inhibitor) were examined. Both inhibitors blocked the inhibitory effect of GRe on ICC pacemaker activity. L-NG-nitroarginine methyl ester (100 mu M), which is a nonselective nitric oxide synthase (NOS) inhibitor, blocked the effects of GRe on ICC pacemaker activity and GRe-stimulated cGMP production in ICCs. Conclusion: In cultured murine ICCs, GRe inhibits the pacemaker activity of ICCs via the ATP-sensitive potassium (K+) channel and the cGMP/NO-dependent pathway. Ginsenoside Re may be a basis for developing novel spasmolytic agents to prevent or alleviate GI motility dysfunction. Copyright (C) 2015, The Korean Society of Ginseng, Published by Elsevier. All rights reserved.
引用
收藏
页码:314 / 321
页数:8
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