Byung Joo Kim a, Hyungwoo Kim b, Guem San Lee c, Insuk So d, Seon Jeong Kim e
a Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 626-870, Republic of Korea
b Division of Pharmacology, Pusan National University School of Korean Medicine, Yangsan 626-870, Republic of Korea
c Wonkwang University College of Korean Medicine, Iksan 570-749, Republic of Korea
d Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea
e Center for Bio-Artificial Muscle and Department of Biomedical Engineering, Hanyang University, Seoul 133-791, Republic of Korea
*Corresponding author.E-mail: sjk@hanyang.ac.kr.
원문 링크 : http://www.sciencedirect.com/science/article/pii/S0378874114004723
Abstract
Ethnopharmacological relevance: San-Huang-Xie-Xin-Tang(SHXXT)isatraditionalChinesemedicinal
formula composedofCoptidisrhizoma(Coptis chinesis Franch),Scutellariaeradix(Scutellaria baicalensis
Georgi), andRheirhizoma(Rheum officinale Baill) andiswidelyusedinEasternAsia,especiallyto
amelioratethesymptomsofgastrointestinal(GI)disordersrelatedtogastritis,gastricbleeding,peptic
ulcers, andabnormalGImotility
Aim ofthestudy: InterstitialcellsofCajal(ICCs)arepacemakercellsintheGItractthatgeneraterhythmic
oscillations inmembranepotentialsknownasslowwaves.BecauseGIdisorders,especiallyabnormalGI
motility,aremajorlifelongproblems,theauthorsinvestigatedtheeffectsofSHXXTonmousesmall
intestine ICCs,andsoughttoidentifythereceptorsandtheactionmechanismsinvolved.
Materials andmethods: Enzymatic digestionswereusedtodissociateICCsfromsmallintestines,andthe
whole-cell patch-clampconfigurationwasusedtorecordpotentialsgeneratedbyculturedICCs.
Results: SHXXT producedmembranedepolarizationincurrent-clampmode,andY25130(a5-HT3
receptorantagonist)andRS39604(a5-HT4 receptorantagonist)blockedSHXXT-inducedmembrane
depolarizations, whereasSB269970(a5-HT7 receptorantagonist)didnot.However,duringexternalCa2þ
free conditionsorinthepresenceofthapsigargin,SHXXTdidnotexhibitmembranedepolarization.
Furthermore,theapplicationof flufenamic acid(anonselectivecationchannel(NSCC)blocker)orDIDS
(a chloridechannelblocker)abolishedpacemakerpotentialgenerationandblockedSHXXT-induced
membrane depolarizations.Inaddition,SHXXT-inducedmembranedepolarizations,whicharedepen-
dent onG-protein,inICCswereblockedbyPD98059(ap42/44mitogen-activatedproteinkinase(MAPK)
inhibitor), SB203580(ap38MAPKinhibitor),andbyac-junNH2-terminalkinase(JNK)IIinhibitor.
RegardingthecomponentsofSHXXT,CoptidisrhizomeandRheirhizomamodulatedICCpacemaking
activity,whereasScutellariaeradixdidnot.
Conclusion: SHXXT modulatespacemakerpotentialsvia5-HT3 and 5-HT4 receptor-mediatedpathways,
externalCa2þ influx, andCa2þ release frominternalstores.Furthermore,NSCCsandCl-channelsplay
important rolesintheregulationofpacemakingactivityinaMAPKdependentmannerinICCs.The
regulation ofpacemakingactivitybySHXXTmaybeduetotheactivityofCoptidisrhizomeandRhei
rhizome. ThestudyshowsSHXXTcanmodulatethepacemakingactivityofICCsintheGItract,andthus,
suggests SHXXThaspotentialpharmacologicalrelevanceforthetreatmentofGImotilitydisorders.