2013-10-15神经递质 组胺等_wjj.ppt

Chapter12OtherneurotransmittersWangJijiangSectionI:HistamineRecognitionofhistamineasanintercellularmessenger:Anaphylaxis(allergy)ArousalDistributionPeripheral:mastocyte,basicyte.Central:Neuronalhistamineintuberomammillarynucleus(TMN).Non-neuronalhistamine:mastocyte,gliacell,endothelialcellH2-receptorantagonistsasdrugscuringpepticulcerMechanismofactionCompetitivelyblockthehistamine(H2)receptorofacid-producingparietalcellsrenderingcellslessresponsivetonotonlyhistaminebutalsotothestimulationofacetylcholineandgastrin.Alsoupto90%pleteinhibitionhasnotbeenshownH2-receptorantagonistsFourFDA-approved:Cimetidine西咪替丁（Tagamet®）Ranitidine雷尼替丁（Zantac®）Famotidine法莫替丁（Pepcid®）Nizatidine尼扎替丁（Axid®）Roxatidine罗沙替丁TheL-amino-acid-transporterbringshistidineintoneuronswherehistamineissynthesizedbythespecificenzymehistidinedecarboxylase.Histamineisthentakenupintovesiclesbythevesicularmonoamine-transporterVMAT-2.Afterrelease,histamineismethylatedbyhistaminemethyltransferasewhichislocatedpostsynapticallyandinglia—totele-methylhistamine,ametabolitethatdoesnotshowanyhistamine-likeactivity.1.Histaminetransportandmetabolisminneurons2.Histaminergicneurons1)Locationandprojections:localizeddistributionofcellbodyandwidespreadprojectionsofmonoaminergicsystems.2)Sitesofsynapses:dendrites(predominately),cellbody(less).3)Co-localizationwithotherneurotransmittersandneuro-modulators2.Histaminergicneurons4)Firingproperties:Spontaneouslyactive:pace-makerproperty.Mechanism:persistentsodiumcurrent;voltage-gatedcalciumcurrent.b.Lowfiringfrequency:LongerAPduration.Obviousafterhyperpolariztion(AHP):voltage-gatedKcurrent,calcium-dependentKcurrent.e.H3autoreceptorsregulatethefiringrate:inhibitionofVDCCs.I-clampV-clamp(H3receptorantagonist)Pleasedescribethefiringpropertiesofhistaminergicneuronsandthemechanisms.Question3.Histaminergicreceptorshyperpolarizing-activatedcationcurrentH1receptors.DepolarizationofaneuronofthepontinereticularformationthroughblockofaK+conductance.H2receptors.Blockofthelong-lastingafterhype