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ß-NicotinicAcetylcholineReceptorContributestotheWoundRepairoftheRespiratoryEpitheliumbyModulatingIntracellularCalciuminMigratingCells
【摘要】Nicotinicacetylcholinereceptors(nAChRs),presentinhumanbronchialepithelialcells(HBECs),havebeenshowninvitrotomodulatecellshape.Becausecellspreadingandmigrationareimportantmechanismsinvolvedintherepairofthebronchialepithelium,weinvestigatedthepotentialroleofnAChRsinthewoundrepairofthebronc...
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ExpressionofNigrostriatal6-ContainingNicotinicAcetylcholineReceptorsIsSelectivelyReduced,butNotEliminated,by3SubunitGeneDeletion
...,Colorado(J.M.M.)AbstractmRNAsfortheneuronalnicotinicacetylcholinereceptor(nAChR)6and3subunitsareabundantlyexpressedandcolocalizedindopaminergiccellsofthesubstantianigraandventraltegmentalarea.Studiesusingsubunit-nullmutantmicehaveshownthat6-or3-dependentnAChRsbind-conotoxinMII(-CtxMII)withhighaffin...
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不同化学结构肌松药对骨骼肌成人型和胎儿型乙酰胆碱受体的作用
...药主要作用于神经肌肉突触后膜的烟碱型乙酰胆碱受体(nAChR),阻断神经冲动的传导,从而使肌肉松弛。突触后膜的乙酰胆碱受体存在两种亚型即存在于健康成人肌细胞突触后膜的成人型乙酰胆碱受体(ε-nAChR)和存在于胎儿和某些病...
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2-Fluoro-3-(4-nitro-phenyl)deschloroepibatidineIsaNovelPotentCompetitiveAntagonistofHumanNeuronal42nAChRs
...).Thechallengeistodesignanalogsthataredevoidofepibatidine‘stoxicityandlownAChRsubtypeselectivity.Effortstomodifyepibatidine‘sstructureincludechangesinstereochemistry,replacementoftheN-Hwithothergroups,changesinthe2-chloropyridinering,replacementofthe2-chloropyridineringwithbioisostericrings,chan...
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42NicotinicReceptorswithHighandLowAcetylcholineSensitivity:Pharmacology,Stoichiometry,andSensitivitytoLong-TermExposuretoNicotine
【关键词】42NicotinicReceptors4and2nicotinicacetylcholinereceptor(nAChR)subunitsexpressedheterologouslyassembleintoreceptorswithhigh(HS)andlow(LS)sensitivitytoacetylcholine(ACh);theirrelativeproportionsdependonthe4to2ratio.Inthisstudy,injectionofoocyteswith1:104/2subunitcDNAratiosfavoredexpress...
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第二军医大学CellRes发表免疫研究新发现
...,ACh(AChR)跨膜受体可以分为毒蕈碱AChRs(mAChRs)和烟碱AChRs(nAChRs)两类。mAChRs是一种G蛋白偶联受体,而nAChRs是一种阳离子通道。α7nAChR是在大脑中最为丰富的一种nAChRs,并且在包括上皮细胞、内皮细胞、免疫细胞和一些癌细胞等许多...
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RoleintheSelectivityofNeonicotinoidsofInsect-SpecificBasicResiduesinLoopDoftheNicotinicAcetylcholineReceptorAgonistBindingSite
...relatedneonicotinoidsactselectivelyoninsectnicotinicacetylcholinereceptors(nAChRs).Toinvestigatethemechanismofneonicotinoidselectivity,wehaveexaminedtheeffectsofmutationstobasicaminoacidresiduesinloopDofthenAChRacetylcholine(ACh)bindingsiteontheinteractionswithimidacloprid.Thereceptorsinvestigatedar...
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SpeciesSelectivityofaNicotinicAcetylcholineReceptorAgonistIsConferredbyTwoAdjacentExtracellular4AminoAcidsthatAreImplicatedintheCoupling
...-4-yl)methyl-1H-quinolin-2-one(TMAQ)isanovelnicotinicacetylcholinereceptor(nAChR)agonistwithstrongselectivityfor4-containingreceptors.TMAQalsoexhibitsremarkablespeciesselectivity,beingapotentagonistofnAChRscontainingthehuman4subunitbuthavingnodetectableagonistactivityonnAChRscontainingtherat4subunit...
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StructuralDeterminatesforApolipoproteinE-DerivedPeptideInteractionwiththe7NicotinicAcetylcholineReceptor
【关键词】StructuralNeuronalnicotinicacetylcholinereceptor(nAChR)signalinghasbeenimplicatedinavarietyofnormalcentralnervoussystem(CNS)functionsaswellasanarrayofneuropathologies.PreviousstudieshavedemonstratedbothneurotoxicandneuroprotectiveactionsofpeptidesderivedfromapolipoproteinE(apoE).Ithas...
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Splenectomyinactivatesthecholinergicantiinflammatorypathwayduringlethalendotoxemiaandpolymicrobialsepsis
...agesthroughamechanismdependentonthe7nicotinicacetylcholinereceptorsubunit(7nAChR)(8,11,12).ElectricalvagusnervestimulationfailstoreduceserumTNFlevelsin7nAChR-deficientmice,andmacrophagesderivedfromtheseknockoutmiceareinsensitivetothecytokine-inhibitingeffectsofcholinergicagonists,indicatingthatthe7n...
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Deletionofthe7,2,or4NicotinicReceptorSubunitGenesIdentifiesHighlyExpressedSubtypeswithRelativelyLowAffinityfor[3H]Epibatidine
...higher-affinity[3H]epibatidinebindingsites.Nicotinicacetylcholinereceptors(nAChRs)areligand-gatedionchannelsthatareexpressedinskeletalmuscle,autonomicganglia,andthecentralnervoussystem(Lindstrom,2000).Thesereceptorsinfluencesimpleandcomplexbehaviors(Picciotto,2003)andshort-andlong-termresponsestonic...
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α7尼古丁胆碱受体的分子成像:放射性配体[18F]NS10743的设计与评价
...一篇文章报道了一种可以定量分析α7尼古丁胆碱受体(α7nAChR)的示踪剂。在α7尼古丁胆碱受体(α7nAChR)激动剂NS10743(4-[5-(4-fluoro-phenyl)-[1,3,4]oxadiazol-2-yl]-1,4-diaza-bicyclo[3.2.2]nonane)上引入放射性同位素,体内外分析其结合特性。...
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AnalogsofMethyllycaconitineasNovelNoncompetitiveInhibitorsofNicotinicReceptors:PharmacologicalCharacterization,ComputationalModeling,andPharmac
...velapproachtodrugdiscoveryinvolvingneuronalnicotinicacetylcholinereceptors(nAChRs),ourlaboratorytargetednonagonistbindingsites(i.e.,noncompetitivebindingsites,negativeallostericbindingsites)locatedonnAChRs.Culturedbovineadrenalcellswereusedasneuronalmodelstoinvestigateinteractionsof67analogsofmethyl...
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Sazetidine-A,ANovelLigandThatDesensitizes4β2NicotinicAcetylcholineReceptorswithoutActivatingThem
【关键词】Sazetidine-ANeuronalnicotinicacetylcholinereceptors(nAChRs)areligand-gatedionchannelsfoundthroughoutthecentralandperipheralnervoussystems.Theyarecrucialtonormalphysiologyandhavebeenclearlyimplicatedinnicotineaddiction.Inaddition,theyarepossibletherapeutictargetsinawiderangeofpathologi...
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NigrostriatalDamagePreferentiallyDecreasesaSubpopulationof62*nAChRsinMouse,Monkey,andParkinson‘sDiseaseStriatum
...paminergicnerveterminals.Theseincludethe62*nicotinicacetylcholinereceptors(nAChRs),whicharelocalizedexclusivelyondopamineterminalsinstriatum(*denotesthepresenceofpossibleadditionalsubunits).Inthisstudy,weusedanovel-conotoxinMII(-CtxMII)analogE11Atofurtherinvestigate62*nAChRsubtypesinmouse,monkey,and...
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DistinctProfilesof7nAChRPositiveAllostericModulationRevealedbyStructurallyDiverseChemotypes
...关键词】DistinctSelectivemodulationof7nicotinicacetylcholinereceptors(nAChRs)isthoughttoregulateprocessesimpairedinschizophrenia,Alzheimer‘sdisease,andotherdementias.Oneapproachtotarget7nAChRsisbypositiveallostericmodulation.Structurallydiversecompounds,includingPNU-120596,4-naphthalene-1-yl-3...
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吸烟者比非吸烟者烟碱受体密度增大:2-18F-FA-85380-正电子发射断层扫描(PET)检查
...烟者脑内非吸烟者含有的烟碱高亲和力的乙酰胆碱受体(nAChRs)密度高。尸脑研究显示吸烟者脑内多个区域比非吸烟者或曾经吸烟但已戒烟者含有的烟碱高亲和力的乙酰胆碱受体(nAChRs)密度高,Maryland的研究人员则运用2FA和PET扫描进...
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PNAS:戒烟为什么那么难?
...研究已经证明了尼古丁与大脑中的尼古丁乙酰胆碱受体(nAChRs)结合,随着时间的推移,持续的结合可能改变神经回路从而促进成瘾。尼古丁乙酰胆碱受体(nAChRs)的α3、β4和α5亚单位在重尼古丁使用和复吸方面起到了关键的作...
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研究发现尼古丁通过糖类对神经起作用
...获得好处。研究首次提供了老鼠的尼古丁乙酰胆碱受体(nAChR)部分详细结构,nAChR属于一类很重要的分子,它们充当离子通道蛋白,使信号在两个神经元间传递。而研究结果显示糖分子在这种蛋白中起到了重要作用。分子和计...
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ExpressionofNative34NeuronalNicotinicReceptors:BindingandFunctionalStudiesInvestigatingTurnoverofSurfaceandIntracellularReceptorPopulations
...onsinvolvealterationsinexpressionofneuronalnicotinicacetylcholinereceptors(nAChRs).AlthoughsomestudieshaveaddressedprocessesinvolvedwithmusclenAChRexpression,knowledgeoftheregulationofneuronalnAChRsisparticularlysparse.Thefollowingstudiesweredesignedtoinvestigatecellularmechanismsinvolvedwithexpress...
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Decreasein3/6NicotinicReceptorsbutNotNicotine-EvokedDopamineReleaseinMonkeyBrainafterNigrostriatalDamage
...ityofUtah,SaltLakeCity,Utah(J.M.M.)AbstractNicotinicacetylcholinereceptors(nAChRs)aredecreasedinthestriataofpatientswithParkinson‘sdisease(PD)orinexperimentalmodelsafternigrostriataldamage.BecausepresynapticnAChRsonstriataldopamineterminalsmediatedopaminerelease,receptorlossmaycontributetobehavior...
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TheEndocannabinoidAnandamideInhibitstheFunctionof4β2NicotinicAcetylcholineReceptors
...nylethanolamide,AEA)onthefunctionof4β2nicotinicacetylcholinereceptors(nAChR)stablyexpressedinSH-EP1cellswereinvestigatedusingthewhole-cellpatch-clamptechnique.Intheconcentrationrangeof200nMto2µM,AEAsignificantlyreducedthemaximalamplitudesandincreasedthedesensitizationofacetylcholine(ACh)-...
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RIC-3EnhancesFunctionalExpressionofMultipleNicotinicAcetylcholineReceptorSubtypesinMammalianCells
...se(ric-3),canenhancefunctionalexpressionof7nicotinicacetylcholinereceptors(nAChRs).Inthepresentstudy,theinfluenceofC.elegansandhumanRIC-3uponmultiplehomomeric(7,8,and9)andheteromeric(32,34,42,44,and910)nAChRsubtypeshasbeenexaminedintransfectedmammaliancellsbyradioligandbindingandfunctionalcharacteri...
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UntranslatedRegion-DependentExclusiveExpressionofHigh-SensitivitySubformsof42and32NicotinicAcetylcholineReceptors
【关键词】Untranslated42nicotinicacetylcholinereceptors(nAChRs)arerecognizedastheprincipalnicotinebindingsiteinbrain.Recombinant42nAChRdemonstratebiphasicconcentration-responserelationshipswithlow-andhigh-EC50components.Thisstudyshowsthatuntranslatedregions(UTR)caninfluenceexpressionofhigh-sens...
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Long-TermNicotineTreatmentDecreasesStriatal6NicotinicAcetylcholineReceptorSitesandFunctioninMice
...Utah(J.M.M.)Abstract-ConotoxinMII-sensitivenicotinicacetylcholinereceptors(nAChRs)aredistinctfromothersubtypesintheirrelativelyrestrictedlocalizationtothestriatumandsomeotherbrainregions.TheeffectofnicotinetreatmentonnAChRsubtypeshasbeenextensivelyinvestigated,withtheexceptionofchangesin-conotoxinMI...
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Are910NicotinicAcetylcholineReceptorsaPainTargetfor-Conotoxins?
...nproposedthattheprimarytargetofVc1.1isthe910nicotinicacetylcholinereceptor(nAChR).WeshowthatVc1.1anditspost-translationallymodifiedanalogsvc1a,[P6O]Vc1.1,and[E14]Vc1.1areequallypotentatinhibitingACh-evokedcurrentsmediatedby910nAChRs.Thissuggeststhat910nAChRsareunlikelytobethemolecularmechanismorther...
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精神疾病药物研发面临困境
...坚实的联系。最典型的例子就是α7烟碱型乙酰胆碱受体(nAChR),该受体被认为是改善精神分裂症认知症状的重要靶点。对动物采用α7nAChR刺激可提升听觉-运动门控系统,而精神分裂症听觉-运动门控系统是缺失的,因此α7nAChR备受...
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EffectsofQuinine,Quinidine,andChloroquineon910NicotinicCholinergicReceptors
...merquinidine,andchloroquineon910-containingnicotinicacetylcholinereceptors(nAChRs).Thecompoundsblockedacetylcholine(ACh)-evokedresponsesin910-injectedXenopuslaevisoocytesinaconcentration-dependentmanner,witharankorderofpotencyofchloroquine(IC50=0.39e)quinine(IC50=0.97e)quinidine(IC50=1.37e).Moreover...
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SubunitCompositionofNicotinicReceptorsinMonkeyStriatum:EffectofTreatmentswith1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineorL-DOPA
...tyofUtah,SaltLakeCity,Utah(J.M.M.).AbstractNicotinicacetylcholinereceptors(nAChRs)representanimportantmodulatorofstriatalfunctionbothundernormalconditionsandinpathologicalstatessuchasParkinson‘sdisease.BecausedifferentnAChRsubtypesmayhaveuniquefunctions,immunoprecipitationandligandbindingstudieswe...
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聚集蛋白基因转染促进移植肌肉功能恢复的实验研究
...神经源性agrin蛋白表达,以及终板区烟碱型乙酰胆碱受体(nAChR)数量的变化。结果术后早期agrin基因转染组肌肉功能恢复明显优于空质粒转染组以及生理盐水注射组(4、5、10周,P<0.05),但术后晚期15及20周时各组肌肉功能间差异无...