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简介:Inmanytissuestheparasympatheticandsympatheticnervoussystemregulatesmoothmusctoneviatheirtransmittersaeetylcholineandnoradrenaline,respectively.Directsmoothmusceeeffectsofacetylcholineviamuscarinicreceptorsalwayspromotecontraction,butnon-neuronalsourcescanimportantlycontributetosuchstimulation.Directsmoothmuscleeffectsofnoradren-alinecanpromotecontractionviaal-andsometimesalsoα2-adrenoceptorsbutcanpromotere-laxationandinhibitcontractionviaβ-adrenoceptors.Iwillfocusontheinteractionbetweensub-typesofmuscarinicandβ-adrenergicreceptors,largelyusingtheurinarybladderasanexam-ple.
简介:Modulationbybalancingactivatingandinhibitoryreceptorsconstitutesanimportantmechanismforregulatingimmuneresponses.Cellsthatareactivatedfollowingligationofreceptorsbearingimmunoreceptortyrosine-basedactivationmotifs(ITAMs)canbenegativelyregulatedbyotherreceptorsbearingimmunoreceptortyrosine-basedinhibitionmotifs(ITIMs).Humanmastcells(MCs)arethemajoreffectorcellsoftypeIhypersensitivityandimportantparticipantsinanumberofdiseaseprocesses.Antigen-mediatedaggregationofIgEboundtoitshigh-affinityreceptoronMCsinitiatesacomplexseriesofbiochemicaleventsleadingtoMCactivation.WithgreatdetaileddescriptionandanalysisofseveralinhibitoryreceptorsonhumanMCs,acentralparadigmofnegativeregulationofhumanMCactivationbythesereceptorshasemerged.Cellular&MolecularImmunology.2004;1(6):408-415.
简介:Coactivatorsandcorepressorsregulatetranscriptionbycontrollinginteractionsbetweensequence-specifictranscriptionfactors,thebasaltranscriptionalmachineryandthechromatinenvironment,Thisreviewconsidertheaccessofnuclearandsteroidreceptorstochromatin,theiruseofcorepressorsandcoactivatorstomodifychromatinstructureandtheimplicationsfortranscriptionalcontrol.Theassemblyofspecificnucleoproteinarchitecturesandtargetedhistonemodificationemergeascentralcontrollingelementsforgeneexpression.
简介:Hormonesandtheirreceptorsregulatecellgrowth,differentiationandapoptosisandalsoplayimportantrolesinimmunefunction.Recentstudiesonthesubfamilyoftheorphannuclearreceptorsknownasretinoid-acidrelatedorphanreceptors(ROR)haveshedimportantinsightsontherolesofthisgroupofnuclearproteinsinthedevelopmentandfunctionoftheimmunesystem.RORαregulatesinflammatorycytokineproductioninbothinnateandadaptiveimmunesystemwhileRORγregulatesthenormaldevelopmentofTlymphocyterepertoireandsecondarylymphoidorgans.Cellular&MolecularImmunology.2004;1(6):401-407.
简介:三3,3-di(4-substituted-phenyl)-1,1-isophthaloylbis(thiourea)混合物作为新奇中立阴离子受体被设计,并且在好收益由简单步骤综合了。受体1的单个晶体结构证明一个溶剂分子被主人分子通过分子间的氢结合捕获。而且,它作为为存在的一个超分子的系统自我装配丰富内部--并且intramolecular氢结合并且-在苯基组之间的相互作用。他们阴离子受体被检验了由的申请紫外力并且1HNMR光谱学,证明他们比另外的卤化物为氟化物有一种更高的选择。主人和客人在第一个步骤通过氢结合相互作用形成了1:1stoichiometry建筑群,然后在F的过量的存在跟随deprotonation的一个过程吗?在DMF的溶剂。
简介:Curativetherapyforspinalcordinjury(SCI)remainselusive,howeveridentifyingoptionsfortailoredtreatmentstrategiesisinfullswing.Likeinthebraintherearedistinctregionsintheadultspinalcordthatharborneuralprogenitorcells(NPCs)(Horneretal.,2000).Thisoffersthepossibilityofrecruitingthesecellsinreparativeapproachestosupportendogenousspinalcordregenerativecapacities.Hereby,one
简介:ObjectivesToinvestigatetheexpressionofhistamineH1receptors(H1R)inthevestibularnucleusofbrainsteminratsandtheroleofH1Rinmotionsickness(MS).MethodsAtotalof24healthySprague-Dawleyratsweredividedrandomlyintofourgroups(n=6each)whichdeterminediftheanimalswouldreceiveinductionofMSordrug(promethazine)treatment:MS(-)/Drug(-);MS(+)/Drug(-);MS(-)/Drug(+at0.25mg);andMS(+)/Drug(+).MSwasinducedbycomplexmotionstimulationandtheconditionedtasteaversionwasusedasabehavioralindicatorofMS.Thevolumeof0.15%sodiumsaccharinsolution(SS)intakewithin45minutesaftermotionstimulationwasmeasured.H1Rinthevestibularnucleuswasexaminedbyimmunofluorescencestaining.TheexpressionofH1Rproteininbrainstemtissueatvestibularnucleuslevelwasdetectedbywesternblot.ResultsThemeanSSintakevolumeintheMS(+)/Drug(-)group(8.8ml)wassignificantlylessthanthatoftheMS(-)/Drug(-)group(15.1ml)(P<0.01).ThemeanSSintakevolumeoftheMS(-)/Drug(+)group(14.8ml)wassimilartothatoftheMS(-)/Drug(-)group.ThemeanSSintakevolume(9.6ml)oftheMS(+)/Drug(+)groupwasmorethanthatoftheMS(+)/Drug(-)group(P<0.01),butlessthanthatoftheMS(-)/Drug(-)grouporMS(-)/Drug(+)group(P<0.01).ImmunofluorescencestainingshowedpositiveexpressionofH1Rinthevestibularnucleusofbrainstemandtheexpressionwasenhancedbymotionstimulation.WesternblotanalysisshowedthatH1Rproteinexpressedinthebrainstemtissueatvestibularnucleuslevelandtheexpressionalsoincreasedsignificantlyaftermotionstimulation.TheMS-inducedincreaseofH1Rwasnotaffectedsignificantlybypromethazine.ConclusionsH1RsexistinthevestibularnucleusinratsandH1Rexpressionisup-regulatedbymotionstimulation,butnotaffectedbypromethazine.ThefindingsindicatethatthehistaminergicsystemisinvolvedinMS.Promethazine,asanH1Rblocker,mayplayitsanti-MSrolebycompetingthebindingsiteon
简介:在病原体识别的像使用费的受体(TLR)的角色在最近的年里是快速地先进的。然而,进在非传染的织物损害的TLR的功能的调查刚开始了。以前,我们和其它表明了那碎裂的hyaluronan(哈)在织物损害期间积累。CD44被要求在织物损害期间清除HA,并且损害了清理哈在不停的发炎的结果。另外,碎裂哈在损害地点由煽动性的房间刺激煽动性的基因的表示。最近,我们识别了那哈碎片要求TLR2和TLR4刺激老鼠巨噬细胞生产煽动性的chemokines和cytokines。在一个非传染的肺损害模型,在TLR2和TLR4缺乏的老鼠显示出煽动性的房间的损害transepithelial迁居,增加的织物损害,提高的肺上皮的房间apoptosis,和减少的幸存。在高分子的质量的表示上的肺上皮的房间哈对尖锐的肺损害和apoptosis的保护的老鼠,部分地通过NF-kappaB的TLR依赖的基础激活。在TLR2和TLR4的夸大的损害缺乏的老鼠看起来由于上皮的房间上的损害HA-TLR相互作用。这些研究识别那个主机矩阵部件哈并且TLR相互作用提供开始煽动性的回答的信号,维持上皮的房间完整,并且支持从尖锐的肺损害的恢复。房间研究(2006)16:693-701。做i:10.1038/sj.cr.7310085;出版联机2006年8月8日。
简介:Thenuclearreceptorsuperfamilyandthetranscriptionalfactorsassociatedwithcytokinesareinherentlydifferentfamiliesofsignalingmoleculesandactivategenetranscriptionbybindingtotheirrespectiveresponsiveelement.However,ithasbecomeincreasinglyclearfromourworksandothersthatnuclearreceptorsareimportantregulatorsofcytokineproductionandfunctionthroughcomplexandvariedinteractionsbetweenthesedistincttranscriptionalfactors.Thisreviewprovidesageneraloverviewofthemechanismofactionofnuclearreceptorsandtheirtranscriptionalcrosstalkwithtranscriptionalfactorsassociatedwithcytokinetransductionpathways.Oneofthemostimportantmechanisticaspectsisproteintoproteininteractionthroughadirectorco-regulator-mediatedindirectmanner.Suchcrosstalkiscruciallyinvolvedinphysiologicalandtherapeuticrolesofnuclearreceptorsandtheirligandsinimmunity,inflammationandcytokine-relatedtumors.Cellular&MolecularImmunology.2004;1(6):416-424.
简介:ObjectiveTostudytheeffectofsalicylateontheexpressionandfunctionofNMDAreceptorsinspiralganglionneurons(SGNs).MethodsThemRNAofNR1subunitofNMDAreceptorinmodiolustissuesweredetectedbyRealtimefluorescencequantitativePCR(FQ-PCR).NMDAreceptorwhole-cellcurrentswererecordedusingpatchclampinacuteisolatedSGNs.ResultsComparedwiththecontrolgroup,salicylatesignificantlyincreasedthemRNAlevelofNR1subunitinSGNs.NMDAofconcentrationsrangingfrom0.1mMto10mMevokednocurrentinSGNs.NMDA(0.1mMand0.5mM)appliedwithsalicylate(5mM),however,inducedinwardcurrents(212.6±15.2pA,n=5;607.9±44.3pA,n=5)inadose-dependentmanner,whichcouldbeinhibitedbyAPV.SalicylatealonedidnotproduceanycurrentinSGNs.ConclusionSalicylateincreasestheexpressionofNMDAreceptorsandfacilitatesthecurrentsmediatedbyNMDAreceptorsinSGNs.
简介:Two-armedneutralanionreceptors(4,5),calix[4]arenesbeatingthioureaandamidebindingsites,werepreparedandexaminedtheiranion-bindingabilitybytheUV-visspectra.Theresultsofnon-linearcurvefittingandJobplotindicatethat4or5forms1:1stoichiometrycomplexwithfluoridebyhydrogenbondinginteractions.Receptors4and5haveanexcellentselectivityforfluoridebuthavenobindingabilitywithacetate,dihydrogenphosphateandthehalogenanions(Cl^-,Br^-,I^-).
简介:Hemocytecountsandphenoloxidase(PO)activitywereexaminedafterhemolymphbeingincubatedindopamine(DA),noradrenaline(NE)andserotonin(5-HT).Resultsshowedthatallthethreebiogenicamines(BAs)hadasignificantimpactontotalhemocytecount(THC),differentialhemocytecount(DHC),andintracelluarandextracelluarphenoloxidase(PO)activity.AmongtheseBas,DAhadthestrongesteffectontheaboveparameters,whereas5-HThadtheleasteffect.PreincubationwithD1receptorantagonistSCH23390,D2receptorantagonistSulpirideand1:1admixtureofthetwocouldsignificantlyinhibittheeffectofDAontheseparameters.SCH23390showedastrongerinhibitoryeffectthanSulpiride,andtheadmixtureexhibitedthestrongesteffect.Theseresultssuggestedthatthechangeofhemocytecountandactivationofprophenoloxidase(proPO)systeminLitopenaeusvan-nameihemocytecanberegulatedbyBAs,andDAmodulatesthetwoparametersviaitsreceptors.
简介:原子受体在细胞的环境察觉到,区别,开发,动态平衡,和新陈代谢起一个必要作用并且高度因此被保存到对面多重的种类。在有免疫力的房间的原子受体的反煽动性的角色最近获得了识别。原子受体在myeloid和淋巴的房间起关键作用,特别地在助手CD4+;T房间类型17(Th17)并且规章的T房间(Treg)。Th17和Treg通过他们和表明小径的cytokine的相互作用在细胞的命运上有主要影响。最近的研究强调了在原子受体和已知的cytokine信号之间的相互作用并且这些相互作用怎么在Th17和Treg子集影响主人抄写因素的表示和功能。这评论将在调整Th17/Treg房间命运决心有关原子受体的角色集中于最近的发现。
简介:backgroundIt'sestablishedthatAngiotensinⅡanditsreceptorsareinvolvedinintimalhyperplasiaafterballooninjuryandstentrestenosis.Recentevidencealsosuggeststhatstatinshavesomeanti-intimalhyperplasiaeffects.Inthisstudy,theeffectofRosuvastatinonexpressionofangiotensinⅡreceptorsinrataorticendotheliumafterballooninjuryisthereforeinvestigated.MethodsAll52WistarKyotoratswereestablishedtoaortainjurymodelsby2Fballooncatheter,thenwererandomlydividedintoshamoperationgroup,aortainjurygroupandRosuvastatin-treatmentgroup.After14days,theaorticspecimensoftheanimalswereharvestedandperformedimmunohistochemistryanddeterminationofmolecularbiology.ResultsTheresultsshowedthat(i)The14days-ballooninjuryinducedobviousintimathickening(P<0.01),however,thephenomenonwasreducedby14days-treatmentwithRosuvastatin(P<0.01).(ii)TheexpressionsofangiotentionⅡtypeⅠ(AT1)andtypeⅡ(AT2)receptormRNAandproteinweremarkedlyup-regulatedbytheballooninjury(P<0.01),after14days-treatmentwithRosuvastatin,theexpressionofAT1receptormRNAanditsproteinwasdecreased(P<0.01),buttheexpressionofAT2receptormRNAanditsproteinwasfurtherincreased(P<0.05).ConclusionInthisstudy,weobservedthattheballooninjuryinduced-intimathickeningwasreducedbyRosuvastatininrats,whichmightbelinkedwiththeregulationofexpressionofangiotensinⅡreceptors.
简介:Arachidonicacid-metabolizingenzyme5-lipoxygenase(5-LOX)producespro-inflammatorymediators:leukotrienes(includingcysteinylleukotrienes,CysLTs).5-LOXandCysLTsareinvolvedinthepathophysiologicalprocessafterbraininjury,andtheactionsofCysLTsaremediatedviaactivationoftheirreceptors,CysLT1andCysLT2.Wehaverecentlyreportedtheexpressionsof5-LOX,CysLT1andCysLT2inhumanbrainswithtraumaticinjuryandtumors,andshort-termneuroprotectiveeffectsofCys-LT1antagonistsinstrokemodelsofratsandmice.
简介:AIM:Toexaminetheassociationofgeneticpolymorphisms(-308)G/ATNFα,(+250)A/GLtα,(+36)A/GTNFR1,(+1663)A/GTNFR2withthedevelopmentofprimaryopenangleglaucoma(POAG)amongpeopleinCentralRussia.METHODS:Thestudysampleincluded443individuals,ofwhich252patientswithPOAGand191individualsinthecontrolgroup.Genotypingof(-308)G/ATNFα,(+250)A/GLtα,(+36)A/GTNFR1,(+1663)A/GTNFR2wasperformedusingpolymerasechainreaction.ThedistributionofallelesandgenotypesofthestudiedDNAmarkersinthegroupswasexaminedby2×2contingencytablesandχ2withtheYates'scorrectionforcontinuityandoddsratios(OR)with95%confidenceintervals(CI).RESULTS:Allele(-308)GTNFα(Р=0.01,OR=1.78,95%CI1.12-2.85)wasidentifiedasariskfactorforPOAG.Homozygotes(-308)AATNFαareatalowestriskfordevelopmentofthedisease(Р=0.01,OR=0.0005).ThefollowingcombinationofgeneticvariantsofcytokineswereassociatedwithareducedriskofPOAG:(+1663)ATNFR2and(+250)GLtα(OR=0.34)CONCLUSION:Geneticpolymorphisms(-308)G/ATNFα,(+250)A/GLtα,(+1663)A/GTNFR2associatedwiththedevelopmentofPOAGinthepopulationofCentralRussia.