细胞生理2教学课件

1、Definition and identification of neurotransmitterDiscovering of neurotransmitter Category and distribution of neurotransmitterDefinition of modulatorCoexistence of transmitterMetabolism of transmitterSection Outline1. Neurotransmitter1.1 Definition and identification of neurotransmitterDefinition: A

2、 chemical released from a presynaptic terminal diffuses to another neuron where it causes excitation or inhibition.Is synthesised, stored, and released from neuronsActivates receptors to produce an effect on the post-synaptic cellHas agonist or antagonist to mimic or block its effectsHas its action

3、terminated1.1 Definition and identification of neurotransmitterA chemical substance that:In the night of Easter Saturday, 1921, I awoke, turned on the light, and jotted down a few notes on a tiny slip of paper. Then I fell asleep again. It occurred to me at six oclock in the morning that during the

4、night I had written down something most important, but I was unable to decipher the scrawl. That Sunday was the most desperate day in my whole scientific life. During the next night, however, I awoke again, at three oclock, and I remembered what it was. This time I did not take any risk; I got up im

5、mediately, went to the laboratory, made the experiment on the frogs heart, described above, and at five o clock the chemical transmission of nervous impulse was conclusively proved.- quoted from Loewi, O., From the Workshop of Discoveries, Lawrence: University of Kansas Press, 1953.Otto Loewi 1921Ot

6、to Loewi1873-1961He connected two frogs hearts by a solutionThe electrical stimulation of the first heart affected the second through the solutionConcluded that there was a chemical released that affected the second heart Frogs and hearts* Awarded 1936 Nobel Prize in Physiology or Medicine1.3 Catego

7、ry and distribution of neurotransmitterBiogenic AminesAmino AcidsPeptidesOthersAcetylcholineMonoaminesSerotoninCatecholaminesNoradrenaline/NorepinephrineDopamineAdrenaline/EpinephrineSubstance PATPNitric OxideGlutamateGABAAcetylcholine, AChIn CNS: Distribution: motor neuron, the ascending reticular

8、activating system, thalamus, striatum, hippocampus. Effects: most of them are excitatory. In PNS: Distribution: Cholinergic fibers includes: Somatic nerve fibers (neuromuscular junction)ANS preganglionic fiberParasympathetic postganglionic fiberA few sympathetic postganglionic fiberEffects: excitato

9、ry or inhibitory which depends on its receptorAcetylcholine, AChMonoamine neurotransmitterNoradrenalin, NA and adrenalin, ADopamine, DASerotonin, 5-HTAdrenergic pathwayDopaminergic pathwaySerotoninergic pathwayPeptides neurotransmitterEnkephalin-endorphinDynorphinSubstance PNeurotensinAmino acid neu

10、rotransmittersExcitatory amino acid, EAAGlutamateAspartateInhibitory amino acid, IAAGABAGlycineGlutamate is the major excitatory neurotransmitter which plays an important role in learning and memoryGABA is the major inhibitory neurotransmitter which plays anxiolytic, antiepileptic and anticonvulsant

11、 effects Amino acid neurotransmittersPurine neurotransmitterPurines neurotransmitter: inhibitory neurotransmitter, ATPNitric oxideOthersCarbon monoxide, COHistamine1.4 Definition of modulatorCharacteristics of neuromodulatorGenerated and released by neuron or glia cellModulate presynaptic neurotrans

12、mitter releaseModulate postsynaptic response 1.5 Coexistence of transmitterDales principle:Coexistence of transmitter:NA and neuropeptide YAch and VIP1.6 Metabolism of transmitterAch1.6 Metabolism of transmitterNANA1.6 Metabolism of transmitterDopamine, DA1.6 Metabolism of transmitter2.Neurotransmit

13、ter receptorCholinergic receptorAdrenergic receptor Receptor of neurotransmitter in CNSPresynaptic receptorSection OutlineReceptorCharacteristics of binding of ligand and receptor:SpecificitySaturabilityReversibilityAgonist and antagonistBasis of Neuropharmacology Agonists and AntagonistsAgonistsStr

14、ucturally similar to neurotransmitter to activate receptorAntagonistsAntagonists block receptorDiverse structures often unrelated to neurotransmitterAbout neurotransmitter receptor Different subtypes of receptorPre- and postsynaptic receptor Presynaptic autoreceptorIonotropic receptor G-protein coup

15、led receptor Enzyme coupled receptorDesensitization 2.1 Cholinergic receptorMuscarinic receptor, MNicotinic receptor, NMuscarinic receptorDistribution: Membrane innervated by most parasympathetic postganglionic fiber and few sympathetic postganglionic fiber. Subtypes: M1, M2, M3, M4, M5G-protein cou

16、pled receptorMultiple effects:Antagonist: atropineNicotinic receptorNeuron-type nicotinic receptor, N1 Located at postsynaptic membrane of both sympathetic and parasympathetic ganglia Ligand gated ion channelAntagonist: tubocurarine (N1 and N2) hexamethonium Nicotinic receptorMuscle-type nicotinic r

17、eceptor, N2Located at end plate of neuromuscular junction Ligand gated ion channelAntagonist: tubocurarine (N1 and N2) decamethonium receptor1 receptor2 receptorreceptor1 receptor2 receptor3 receptor2.2 Adrenergic receptorreceptorAction1 receptor: mainly excitatory2 receptor: autoreceptorAntagonistr

18、eceptor: phentolamine (1 2 ) 1 receptor: prazosin2 receptor: yohimbinereceptorAction1 receptor: excitatory2 receptor: inhibitoryAntagonistreceptor: propranolol 1 receptor: practolol2 receptor: butoxamine2.3 Receptor in CNSDA receptor5-HT receptorGlutamate receptorGABA receptorGlycine receptorPeptide

19、 receptorPurine receptorHistamine receptorDopamine receptorG-protein coupled receptorSubtypes: DA1, DA2, DA3, DA4, DA5Action: DA1, DA5cAMP DA2, DA3, DA4 cAMP Antagonist: DA receptor: pimozide DA1 receptor: SCH23390 DA2 receptor: butyrophenonesSerotonin receptor7 families, 5-HT1-714 structurally and

20、pharmacologically distinct subtypes 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT1F5-HT2A, 5-HT2B, 5-HT2C5-HT3: ligand-gated ion channel5-HT45-HT5A, 5-HT5B5-HT65-HT7Antagonist:5-HT: cinanserin5-HT1A: spiperone, methiothepin5-HT3: ICS20930Serotonin receptorGlutamate receptorSubtypes of glutamate receptorNMDAA

21、MPA & KainateMetabotropicGlutamate receptorGlutamate ReceptorsAMPA receptorNMDA receptorGlutamate is important for learning and memoryHigh densities of NMDA and AMPA receptors in the hippocampusRole for glutamate receptors in long term potentiationGlutamate receptor antagonists inhibit LTP and learn

22、ing and memoryAMPA receptor potentiators enhance LTP and learning and memoryField EPSPsHigh-frequency stimulationGABA receptorGABA-A receptor ionotropic receptorGABA-B receptor metabotropic receptorGABA-C receptor ionotropic receptorIonotropic GABA-A receptorAntagonist:BicucullinePicrotoxinGABA-A re

23、ceptors mediate fast inhibitory synaptic potentials7 transmembrane domain Structural model of GABA-B receptor GiCa2+GiCa2+ BaclofenPresynaptic GABA-B receptorGiGiK+K+Postsynaptic GABA-B receptorIonic mechanism of GABA-B receptorGlycine receptorStrychnine sensitive: Cl- channel, IPSPStrychnine insens

24、itive: modulate glutamate receptor2.4 Presynaptic receptorGABAB1GABAB2glutamatergic terminalGABAergic terminalglutamatergic terminalGABAergic terminalGP dendriteGP dendritePresynapticPostsynaptic GABAB receptorsauto-GABAB receptorshetero-GABAB receptorsSummary - NeurotransmissionAch receptorNicotini

25、c receptors (nAchR), ligand-gated, located in autonomic ganglia(N1), neuromuscular junction(N2), Renshaw cell.Muscarinic receptor: metabotropic.M1 Gq IP3/DAG Ca2+ ,in brain, activates myenteric plexus.1.2 Discovering of neurotransmittervagus nerveelectricalstimulationHEART RATE SLOWSHEART RATE SLOWS

26、secreted chemical messenger“Vagusstoff”(acetylcholine)superfusateOtto Loewi1873-1961* Awarded 1936 Nobel Prize in Physiology or MedicineExperiment on frog heart (1921)Acetylcholine, AChNorepinephrine, NE and Epinephrine,E (Catecholamine)Dopamine, DA5-hydroxytryptamine, 5-HTHistamineAmino acids: glut

27、amate, aspartate, -aminobutyric acid, glycinePeptides: substance P, tachykinin,opioid peptide, brain-gut peptidePurines: adenosine, ATPOthers: nitric oxide, NO and carbon monoxide, CO1.3 Category and distribution of neurotransmitter1.1 Definition and identification of neurotransmitterDefinition: A c

28、hemical released from a N.ending diffuses to another N. or effector C. where it causes Exc.or Inh.Criteria: Synthesized or taken up by pre-S-N.Released in sufficient amount to cause Exc. or Inh. Specific receptor on the post-S-N. or effector cell.Mechanism for removal or inactivation.Agonist, antago

29、nist to mimic or block its effects.Pharmacologist are able to develop drugs that regulate somatic, visceral activities, emotion, behaviors. 1.1 Definition and identification of neurotransmitterAcetylcholine, AChIn CNS: Cholinergic neurons are located in motor neuron, the ascending reticular activati

30、ng system, thalamus, striatum, hippocampus. Most of them are excitatory.Alzheimers disease: loss of cholinergic fiber in basal forebrain.The major NE-ergic cell group is locus ceruleus(LC,A6) which contributes most of axons of dorsal NE-ergic bundle in MFB, sending axons to cerebellum, cerebral cort

31、ex, thalamus, hippocampus, hypothalamus, form part of ascending reticular activating system, regulates attention, arousal, circadian rhythms.Noradrenergic PathwaysDopamine, DANigrostriatal tract: substantia nigro pars compacta (SNc) axons caudate nucleus and putamen. This tract triggering of self-in

32、itiated movement and postural adjustments.Arcuate Nucleus axons median eminence release of PRLDopaminergic TractsDopamineDA plays a role in movement, behavioral disorders.Parkinson disease: degeneration of DA-erginc neurons in SNc.Schizophrenia, excess DA release, increased DA receptors, antipsychot

33、ic drugs function by blocking D2 receptors. SerotoninSerotoninSerotonin5-HT plays a role in the following: Mood control (drug that augment serotonergic transmission are used to treat depression, obsessive-compulsive behavior, schizophrenia). Regulation of circadian rhythms. Food intake. 5-HT in Mental illnessWell known drug Prozat (fluxetine hydro-chloride), a serotonin reuptake inhibitor, is used in the treatment of depression.In the US, severe depression affects 18.8 million(9.5%) over 18 years of age and is almost always a factor in the more than 30000 suici