Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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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

  • Hong, Noo Ri (Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine) ;
  • Park, Hyun Soo (Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine) ;
  • Ahn, Tae Seok (Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine) ;
  • Kim, Hyun Jung (Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine) ;
  • Ha, Ki-Tae (Healthy Aging Korean Medical Research Center, Pusan National University School of Korean Medicine) ;
  • Kim, Byung Joo (Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine)
  • Received : 2014.12.08
  • Accepted : 2015.02.25
  • Published : 2015.10.15
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Abstract

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 GI 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 50-[${\beta}-thio$]diphosphate [a guanosine-5'-triphosphate (GTP)-binding protein inhibitor] and by glibenclamide [an adenosine triphosphate (ATP)-sensitive $K^{+}$ channel blocker]. 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.

Keywords

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