【文题】InhibitionofCa2+-activatedandvoltage-dependentK+currentsby2-mercaptophenyl-1,4-naphthoquinoneinpituitaryGH3cellsContributiontoitsantiproliferativeeffect
【杂志】lifescience7020021185-1203
【作者】Mei-HanHuang,Sheng-NanWu,Chi-PienChen,Ai-YuShen
【单位】DepartmentofPharmaceuticalScience,FooYinInstituteofTechnology,Ta-Liao,KaohsiungCounty,Taiwan,R.O.C.DepartmentofMedicalEducationandResearch,KaohsiungVeteransGeneralHospital,KaohsiungCity,TaiwanDepartmentofPharmacy,TajenInstituteofTechnology,Pingtung,Taiwan,R.O.C.
【文摘】Quinoneshavebeenshowntopossessantineoplasticactivity;however,theireffectsonioniccurrentsremainunclear.Theeffectsof2-mercaptophenyl-1,4-naphthoquinone(2-MPNQ),menADIone(MD)and1,4-naphthoquinone(1,4NQ)oncellproliferationandioniccurrentsinpituitaryGH3lactotrophswereinvestigatedinthisstudy.2-MPNQwasmorepotentthanmenadioneor1,4-naphthoquinoneininhibitingthegrowthofGH3cells.2-MPNQdecreasedcellproliferationinaconcentration-dependentmannerwithanIC50valueof3mM.Inwhole-cellrecordingexperiments,2-MPNQreversIBLycausedaninhibitionofCa21-activatedK+current(IK(Ca))inaconcentrationdependentmanner.TheIC50valuefor2-MPNQ-inducedinhibitionofIK(Ca)was7mM.Intheinsideoutconfigurationofsinglechannelrecording,2-MPNQ(30mM)appliedintracellularlysuppressedtheactivityoflarge-conductanceCa21-activatedK+(BKCa)channelsbutdidnotmodifysinglechannelconductance.Menadione(30mM)hadnoeffectonthechannelactivity,whereas1,4-naphthoquinone(30mM)suppresseditbyabout26%.Both2-MPNQandthimerosalsuppressedthedithiothreitol-stimulatedchannelactivity.2-MPNQalsoblockedvoltage-dependentK+currents,butitproducedaslightreductionofL-typeCa21inwardcurrent.However,unlikeE-4031,2-MPNQ(30mM)didnotsuppressinwardlyrectifyingK+currentpresentinGH3cells.Underthecurrentclampconfiguration,thepresenceof2-MPNQ(30mM)depolarizedthecells,andincreasedthefrequencyanddurationofspontaneousactionpotentials.The2-MPNQ-mediatedinhibitionofK+currentswouldaffecthormonesecretionandcellexcitABIlity.Theblockadeoftheseionicchannelsby2-MPNQmaypartlyexplainitsinhibitoryeffectontheproliferationofGH3cells.

【翻译】醌类化合物已经发现具有抗肿瘤的作用，然而它对于离子通道的影响还不是很清楚。此研究的内容是MPNQ和1，4NO的对于垂体瘤GH3细胞的增殖和离子通道方面的影响。2-MPNQ对于GH3细胞的生长抑制作用较甲萘醌和1，4NO更强。2-MPNQ以3uM的浓度能降低细胞增殖的浓度依赖IC50.在全细胞记录的实验中,MPNQ可逆性的引起I(Kca)浓度依赖的抑制。IC50的MPNQ抑制I(Kca)的浓度是7uM。在单一通道的记录中，2-MPNQ(30mM)可以抑制细胞内BKCa的传导，但并不影响单通道的传导。甲萘醌(30mM)对于此通道没有影响，1，4NO在此浓度下的抑制率大约为26％。2-MPNQ和硫柳汞可以抑制二硫苏糖醇刺激性通道的活动。2-MPNQ也可以阻滞电压依赖的钾通道，但对于L型钙通道的内流有轻微的抑制作用。2-MPNQ与E4031不同的是它并不抑制GH3细胞的内流的钾电流。在当前的研究下表明，2-MPNQ可以使GH3细胞增殖，并且能够增加自发动作电位的频率和持续时间。2-MPNQ介导的钾电流的抑制可能会影响到激素的分泌和细胞兴奋性。2-MPNQ对于这些离子通道的阻滞作用可以部分解释它是如何对GH3细胞增殖的抑制作用。

【点评】比较标准的电生理的SCI文章