1 Neurotransmitter Su Bo Institute of neurobiology 0531-88382329; [email protected].

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Neurotransmitter Neurotransmitter

Su BoSu Bo

Institute of neurobiologyInstitute of neurobiology0531-88382329; [email protected]; [email protected]

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OutlineOutline

Neurotransmitter categoriesNeurotransmitter categories

Neurotransmitter chemistryNeurotransmitter chemistry

Some important neurotransmittersSome important neurotransmitters

Discovery of NeurotransmitterDiscovery of Neurotransmitter

1904, Renton Elliott, hypothesis 1904, Renton Elliott, hypothesis neurotransmitter;neurotransmitter;

1914, Henry Dale discovered 1914, Henry Dale discovered acetylcholine;acetylcholine; stimulation of the parasympathetic nervous stimulation of the parasympathetic nervous

system;system; 1920, Otto Loewi (1920, Otto Loewi ( 奥托奥托洛维洛维 ) ;) ; 1929 Dale purified acetylcholine from 1929 Dale purified acetylcholine from

mammalian organsmammalian organs

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1936 Nobel prize winner

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Basic Concepts of NT

NeurotransmitterNeurotransmitter 递质递质 Endogenous signaling molecules that Endogenous signaling molecules that alter alter the the

behaviour of neurons or effector cells.behaviour of neurons or effector cells.

NeuromodulatorNeuromodulator 调质调质 Endogenous signaling molecules that Endogenous signaling molecules that regulateregulate the the

behaviour of neurons or effector cells.behaviour of neurons or effector cells.

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Criteria for neurotransmitterCriteria for neurotransmitter

The molecule must be synthesized The molecule must be synthesized

and stored in the presynaptic neuron.and stored in the presynaptic neuron.

The molecule must be released by The molecule must be released by

the presynaptic axon terminal upon the presynaptic axon terminal upon

stimulation. stimulation.

The molecule ,when experimentally The molecule ,when experimentally

applied, must produce a response in applied, must produce a response in

the postsynaptic cell that mimics the the postsynaptic cell that mimics the

response produced by the release of response produced by the release of

neurotransmitter from the presynaptic neurotransmitter from the presynaptic

neuron.neuron.

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Classical Transmitters Classical Transmitters

(small-molecule transmitters)(small-molecule transmitters)

Large-molecule Large-molecule neurotransmittersneurotransmitters

others others

CholinesCholines AminesAmines Amino acidsAmino acids NeuropeptidesNeuropeptides

Acetylcholine Acetylcholine (Ach)(Ach)

Dopamine (DA)Dopamine (DA) GlutamateGlutamate CCKCCK NONO

EpinephrineEpinephrine（（ EE ））

AspartateAspartate DynorphinDynorphin COCO

Norepinephrine(NENorepinephrine(NE))

GABAGABA EnkephalinsEnkephalins ATPATP

Serotonin (5-HT)Serotonin (5-HT) GlycineGlycine VIPVIP

Histamine(HIS)Histamine(HIS) Neuropeptide YNeuropeptide Y

Substance PSubstance P

Categories of neurotransmittersCategories of neurotransmitters

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Neuropeptides

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OutlineOutline




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Elements of Neurotransmitter SystemElements of Neurotransmitter System

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SynthesisSynthesisSmall-molecule neurotransmitter Neuropeptide

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Vesicular transporterVesicular transporter ATP-dependent H+ accumulationATP-dependent H+ accumulation

Reverse transportReverse transport

VVesicular ACh transporter (VAChT)esicular ACh transporter (VAChT)

VVesicular monoamine transporter (VMAT)esicular monoamine transporter (VMAT)

VVesicular Glu transporter (VGLUT)esicular Glu transporter (VGLUT)

Vesicular inhibitory amino acid transporter (VIAAT)Vesicular inhibitory amino acid transporter (VIAAT)

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small clear-core vesiclessmall clear-core vesicles40-60nm40-60nm

Storage

large dense-core vesicleslarge dense-core vesicles90-250nm90-250nm

Ach, Amino acidsAch, Amino acids Neuropeptides, AminesNeuropeptides, Amines

囊泡储存是递质储存的主要方式囊泡储存是递质储存的主要方式递质合成后储存在囊泡内，囊泡内可以有数千个递质分

子。待释放的活动囊泡聚集在突触前膜活动区，为递质的胞裂外排作好准备– 小分子递质如乙酰胆碱、氨基酸类递质储存在直径

40~60 nm 的小囊泡中，在电镜下囊泡中央清亮，为小的清亮囊泡

– 神经肽储存在直径约 90~250nm 的大囊泡中，电镜下，囊泡中央电子密度较高，为大的致密核心囊泡

– 单胺类递质储存的囊泡既有小的致密核心囊泡，也有大的（直径 60~120 nm ）不规则形状的致密囊泡

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Neurotransmitter Co-existenceNeurotransmitter Co-existence

Dale’s principle:Dale’s principle: A neuron has only one neurotransmitter. A neuron has only one neurotransmitter.

Both a classical neurotransmitter (ACh or

catecholamine) and a polypeptide neurotransmitter exist

in the terminal of one neurons.

They are contained in different synaptic vesicles that can

be distinguished using the electron microscope.

The neuron can thus release either the classical

neurotransmitter or the polypeptide neurotransmitter

under different conditions.

CotransmissionCotransmission CotransmissionCotransmission is the release of several types of is the release of several types of

neurotransmitters from a single nerve terminal.neurotransmitters from a single nerve terminal. Some neurons can release at least two neurotransmitters at the same Some neurons can release at least two neurotransmitters at the same

time, the other being a time, the other being a cotransmittercotransmitter, in order to provide the stabilizing , in order to provide the stabilizing

negative feedback required for meaningful encoding, in the absence of negative feedback required for meaningful encoding, in the absence of

inhibitory interneurons.inhibitory interneurons.

GABA–glycine co-release. GABA–glycine co-release.

Dopamine–glutamate co-release. Dopamine–glutamate co-release.

Acetylcholine–glutamate co-release.Acetylcholine–glutamate co-release.

Glutamate–dynorphin co-releaseGlutamate–dynorphin co-release

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fast 300us

slow 50ms

Release

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CaCa2+2+ dependent Release dependent Release

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Ca2+ dependent release

Fura-2 staining

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Tetanus

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Lambert-Eaton myasthenic syndrome(LEMS)

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Transmitter Termination

Diffusion

Reuptake

Enzymatic degradation: neuropeptidesneuropeptides

Autoreceptor

Combination of above

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Transporter exist in the Transporter exist in the presynaptic membrane presynaptic membrane or the membrane of glia or the membrane of glia surrounding the synapsesurrounding the synapse

Na+/K+-dependent Na+/K+-dependent transportertransporter ：： GlutamateGlutamateNa+/Cl--dependent Na+/Cl--dependent transporter: GABA, Aminestransporter: GABA, Amines

Reuptake

Two Families of Postsynaptic Receptors

Transmitter-gated ion

channels

directly controls

channel

fast

G-protein-coupled

receptors

second messenger

systems

receptor indirectly

controls channel

slow

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Transmitter-gated ion channelsTransmitter-gated ion channels

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The general architecture of ligand-gated receptors

(A)One of the subunits of a complete receptor(B)Assembly of either four or five subunits into a complete receptor

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A diversity of subunits come together to form functional ionotropic receptors

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The basic structure of GPCRThe basic structure of GPCR

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Structure of GPCRsStructure of GPCRs

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These receptor proteins contain

seven transmembrane domains.

Portions of domains II, III, VI, and

VII make up the neurotransmitter-

binding region.

G-proteins bind to both the loop

between domains V and VI and to

portions of the C-terminal region.

Structure of GPCRsStructure of GPCRs

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G-protein-coupled receptorsG-protein-coupled receptors

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The basic mode of operation of G-proteinsThe basic mode of operation of G-proteins

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The basic mode of operation of G-proteinsThe basic mode of operation of G-proteins

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Gs/GiGs/Gi －－ ACAC －－ cAMPcAMP

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Gs AC

ATP cAMP

细胞膜

核膜

C

C

R

R

C

C

R

R

2cAMP

2cAMP+

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ＣＣ

结构基因

ＣＲＥＢ

ＣＲＥＢ

细胞核

PiPi

ＣＲＥＢ

Pi

ＣＲＥＢ

Pi

ＣＲＥDNA

蛋白质生理效应

QIAGENQIAGEN

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Gq-PLC-IP3/DAGGq-PLC-IP3/DAG

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Varieties of metabotropic neurotransmitter receptors

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Agonist and AntagonistAgonist and Antagonist

Each neurotransmitter exerts its postsynaptic Each neurotransmitter exerts its postsynaptic

effects by binding to specific receptors.effects by binding to specific receptors.

Neuropharmacological analysisNeuropharmacological analysis: studying : studying

different receptor subtypes using agonist and different receptor subtypes using agonist and

antagonist.antagonist.

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AgonistAgonist

A substance that mimics a specific neurotransmitter, is

able to attach to that neurotransmitter's receptor and

thereby produces the same action that the

neurotransmitter usually produces.

Drugs are often designed as receptor agonists to treat a

variety of diseases and disorders when the original

chemical substance is missing or depleted.

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Antagonist

Drugs that bind to but do not activate neuroreceptors,

thereby blocking the actions of neurotransmitters or the

neuroreceptor agonists.

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Neuropharmacology of Receptor SubtypesNeuropharmacology of Receptor Subtypes

NeurotransmitterNeurotransmitter Receptor subtypeReceptor subtype AgonistAgonist AntagonistAntagonist

Acetylcholine(ACh)Acetylcholine(ACh) Nicotinic receptorNicotinic receptor NicotineNicotine CurareCurare

Muscarinic receptorMuscarinic receptor MuscarineMuscarine AtropineAtropine

Norepinephrine(NE)Norepinephrine(NE) αα receptor receptor PhenylephrinePhenylephrine PhenixybenzaminePhenixybenzamine

ββ receptor receptor IsoproterenolIsoproterenol PropranololPropranolol

Glutamate(Glu)Glutamate(Glu) AMPAAMPA AMPAAMPA CNQXCNQX

NMDANMDA NMDANMDA AP5AP5

GABAGABA GABAGABAAA MuscimolMuscimol BicucullineBicuculline

GABAGABABB BaclofenBaclofen PhaclofenPhaclofen

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OutlineOutline




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Acetylcholine (ACh)Acetylcholine (ACh)

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ACh systemACh system

Arising from the basal forebrain Arising from the basal forebrain

(( 基底前脑基底前脑 ) and brain stem () and brain stem ( 脑脑干干 ) )

The medial septal nuclei The medial septal nuclei (( 隔内隔内侧核侧核 ) and basal nucleus of ) and basal nucleus of

Meynert project widely upon the Meynert project widely upon the

cerebral cortex (hippocampus)cerebral cortex (hippocampus)

The pontomesencephalo-The pontomesencephalo-

tegmental complex tegmental complex (( 脑桥脑桥 -- 中中脑脑 -- 被盖复合体被盖复合体 ))projects to the projects to the

thalamus and parts of the thalamus and parts of the

forebrainforebrain

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Choline acetyltransferase (ChAT)Choline acetyltransferase (ChAT)

Be manufactured in the soma and transported to the Be manufactured in the soma and transported to the

axon terminalaxon terminal

Only cholinergic neurons contain ChAT: a marker of Only cholinergic neurons contain ChAT: a marker of

chonlinergic neuronschonlinergic neurons

Transport of choline into neuron is the rate-limiting step Transport of choline into neuron is the rate-limiting step

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Acetylcholinesterase (AChE)

Can be manufactured by cholinergic neurons or Can be manufactured by cholinergic neurons or

noncholinergic neuronsnoncholinergic neurons

Specific for ACh degradation and has fast catalytic ratesSpecific for ACh degradation and has fast catalytic rates

Target of pharmacologyTarget of pharmacology

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Ach ReceptorsAch Receptors

ACh is both an excitatory and inhibitory

Nicotinic ACh receptors (Ligand-gated ion channels)

N1(nicotinic neruronal, NN) : all autonomic ganglia and

hormone producing cells of adrenal medulla

N2(nicotinic muscle, NM): neuromuscular junction

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Nicotinic ACh receptorNicotinic ACh receptor

Permeable for

Na+, K+ and little

Ca2+

Depolarization:

EPSP

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Muscarinic ACh receptors (GPCR)Muscarinic ACh receptors (GPCR)

Muscarinic ACh receptors (M1-M5)

Found in the plasma membrane of Found in the plasma membrane of

smooth and cardiac muscle cells, and in smooth and cardiac muscle cells, and in

cells of particular glandscells of particular glands

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Muscarinic ACh receptors (GPCR)Muscarinic ACh receptors (GPCR)

MM11-R: ganglion-R: ganglion

MM22-R: heart-R: heart

MM33-R: exocrine glands, smooth muscle, endothelium -R: exocrine glands, smooth muscle, endothelium

(produce NO)(produce NO)

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MonoamineMonoamine

Catecholamines (CAT)

Dopamine (DA) Norepinephrine (NE) Epinephrine

Serotonin (5-HT)

Histamine

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The biosynthetic pathway The biosynthetic pathway for the catecholaminesfor the catecholamines

TyrosineTyrosine

Tyrosine hydroxylase:Tyrosine hydroxylase:

Rate-limiting enzymeRate-limiting enzyme

a marker of a marker of

catecholaminergic catecholaminergic

neuronsneurons

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Termination Reuptake: NaReuptake: Na++/Cl/Cl---dependent transporter-dependent transporter

Dopamine transporter (DATDopamine transporter (DAT ））

Norepinepherine transporter (NET)Norepinepherine transporter (NET)

Target of different drugs: amphetamine and cocaineTarget of different drugs: amphetamine and cocaine

EnzymaticEnzymatic degradation:degradation:

Monoamine oxidase (MAO): Monoamine oxidase (MAO):

MAOI: antidepressant – phenelzine (MAOI: antidepressant – phenelzine ( 苯乙肼苯乙肼 ) and ) and

tranylcypromine (tranylcypromine ( 强内心百乐明强内心百乐明 ))

Catechol-O-methyl transferase (COMT)Catechol-O-methyl transferase (COMT)

Postsynapse, Synaptic cleftPostsynapse, Synaptic cleft

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Stimulant drug action on the Stimulant drug action on the catecholamine axon terminalcatecholamine axon terminal

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Dopamine (DA)Dopamine (DA) Arising from the Arising from the

substantia nigra and substantia nigra and

the ventral tegmental the ventral tegmental

areaarea （腹侧被盖区）（腹侧被盖区）

Project to the Project to the

striatum (caudate striatum (caudate

nucleus and nucleus and

putamen), limbic and putamen), limbic and

frontal cortical region frontal cortical region

respectively.respectively.

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DA receptorsDA receptors

D1-D5: all are GPCRsD1-D5: all are GPCRs

D1-like receptors: D1 and D5D1-like receptors: D1 and D5

D2-like receptors: D2-like receptors:

D2:D2: domperidone domperidone 多潘立酮多潘立酮

D3: autoreceptorD3: autoreceptor

D4: psychotropic drugs (chlorpromazine D4: psychotropic drugs (chlorpromazine 氯丙嗪氯丙嗪 ))

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Norepinephrine (NE) as NT NE in both PNS and CNSNE in both PNS and CNS PNS: PNS:

Smooth muscles, cardiac muscle and glandsSmooth muscles, cardiac muscle and glands.. Increase in blood pressure, constriction of arteriesIncrease in blood pressure, constriction of arteries

CNS: CNS:

Arising from the Arising from the locus coeruleuslocus coeruleus

（蓝斑核）（蓝斑核） , project to vast area of , project to vast area of

the CNS, including the spinal cord, the CNS, including the spinal cord,

cerebellum, thalamus and cerebral cerebellum, thalamus and cerebral

cortexcortex

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Adrenergic receptorAdrenergic receptor

α1 : α1A 、 α1B 、 α1D

α2: α2A 、 α2B 、 α2C

β : β1 、 β2 、 β3

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　 location function atagonist

α1blood vessels of skin, mucosa, abdominal viscera, kidneys, salivary glands

vasoconstriction, sphincter constriction

Phentolamine ( 酚妥拉明） Prazosin ( 哌唑嗪 )

α2

Membrane of adrenergic axon terminals (pre-synaptic receptors), platelets

inhibition of NE release (autoreceptor);promotes blood clotting, pancreas decreased insulin secretion

Phentolamine ( 酚妥拉明） Yohimbine ( 育亨宾 )

β1 Mainly heart muscle cellsincreased heart rate and strength

Propranolol ( 普萘洛尔 ) Atenolol ( 阿替洛尔 )

β2

Lungs, most other sympathetic organs, blood vessels serving the heart (coronary vessels);

dilation of bronchioles & blood vessels (coronary vessels), relaxation of smooth muscle in uterus

Propranolol ( 普萘洛尔 ) Butoxamine

β3 Adipose tissuestimulation of lipolysis 　

Adrenergic receptorAdrenergic receptor

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Serotonin (5-HT)Serotonin (5-HT)

Arising from the raphe Arising from the raphe

nucleinuclei （中缝核群）（中缝核群） , ,

clustered along the clustered along the

midline of the brain midline of the brain

stemstem

Project extensively to Project extensively to

all levels of the CNSall levels of the CNS

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TryptophanTryptophan

TPH: rate-limiting enzymeTPH: rate-limiting enzyme

SSRI: serotonin reuptake SSRI: serotonin reuptake

inhibitorinhibitor

----antidepressant antidepressant

Fluoxetine Fluoxetine 氟西汀氟西汀 (( 百忧解百忧解 ))

Serotonin (5-HT)Serotonin (5-HT)

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Medications Available to Treat DepressionMedications Available to Treat Depression

Tricyclic antidepressants (TCA): amitriptylineTricyclic antidepressants (TCA): amitriptyline （阿米替林）（阿米替林）

MAO inhibitors (MAOI): moclobemideMAO inhibitors (MAOI): moclobemide （马氯贝胺）（马氯贝胺）

NE reuptake inhibitors (NRI): NE reuptake inhibitors (NRI): maprotilinemaprotiline （马普替林）（马普替林）

SerotoninSerotonin reuptake inhibitors reuptake inhibitors (SSRI): fluoxetineSSRI): fluoxetine （氟西汀）（氟西汀）

Serotonin/NE reuptake inhibitors (SNRI): venlafaxineSerotonin/NE reuptake inhibitors (SNRI): venlafaxine （文拉法新）（文拉法新）

NaSSA: mirtazapineNaSSA: mirtazapine （米氮平）（米氮平）

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5-HT receptors5-HT receptors

GPCR:GPCR: 5-HT5-HT11 －－ Gi: cerebrovascular constriction (migraine) Gi: cerebrovascular constriction (migraine)

5-HT5-HT22 －－ Gq: Gq: vasoconstriction (hypertension)vasoconstriction (hypertension)

Ligand-gated ion channelLigand-gated ion channel 5-HT5-HT33: permeable for Na: permeable for Na++/K/K+ +

（（ ondansetron ondansetron 昂丹司琼）昂丹司琼）

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Amino acidsAmino acids

Excitatory amino acid, EAA

Inhibitory amino acid, IAA

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GlutamateGlutamate

Glutamine cycle

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Glutamate receptorsGlutamate receptors

Ligand-gated ion channelsLigand-gated ion channels

NMDA receptor: NMDA receptor: NN-methyl-D-aspartate (N--methyl-D-aspartate (N- 甲基甲基 -D--D- 天天冬氨酸冬氨酸 ))

AMPA receptor:α-amino-3-hydroxyl-5-methyl-4-AMPA receptor:α-amino-3-hydroxyl-5-methyl-4-

isoxazole-propionate (α-isoxazole-propionate (α- 氨基氨基 -3--3- 羟基羟基 -5--5- 甲基甲基 -4--4- 异异噁唑噁唑 -- 戊酸戊酸 ))

KA receptor: kainic acid (KA receptor: kainic acid ( 海人藻酸海人藻酸 ))

GPCRsGPCRs

mGluRs: metabotropic glutamate receptor 1-7mGluRs: metabotropic glutamate receptor 1-7

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NMDA receptorNMDA receptor

Four subunits: Four subunits:

NR1 and NR2NR1 and NR2

Glycine binding site Glycine binding site

(co-agonist) (co-agonist)

MgMg2+2+ binding site binding site

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NMDA and AMPA NMDA and AMPA receptorreceptor

AMPA receptors are AMPA receptors are permeable to Napermeable to Na++ and K and K++, , not Canot Ca2+2+

AMPA produce fast EPSCAMPA produce fast EPSC

NMDA receptors produce NMDA receptors produce

slower EPSCslower EPSC

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Transmitter-gated Transmitter-gated

and voltage and voltage

dependentdependent

MK-801: open-MK-801: open-channel blockerchannel blocker

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Coexistence of NMDA and AMPA receptorsCoexistence of NMDA and AMPA receptors

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CNQX: 6- 氰基 -7- 硝基喹喔啉 -2 ， 3- 二酮AP5: D-2- 氨基 -5- 磷酸基戊酸

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NMDA receptors are permeable to NaNMDA receptors are permeable to Na++/K/K++//CaCa2+2+

CaCa2+2+ is very important for cell function. It can trigger is very important for cell function. It can trigger

neurotransmitter release, active many enzymes, regulate the neurotransmitter release, active many enzymes, regulate the

opening of a variety of channels, and affect gene expression; opening of a variety of channels, and affect gene expression;

in excessive amounts, Cain excessive amounts, Ca2+2+ can even trigger the death of cell can even trigger the death of cell

((ExcitotoxicityExcitotoxicity).).

Activation of NMDA receptors can cause widespread and Activation of NMDA receptors can cause widespread and

lasting changes in the postsynaptic neuron, especially lasting changes in the postsynaptic neuron, especially long-long-

term memoryterm memory. .

NMDA and AMPA receptorNMDA and AMPA receptor

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GABA (γ-aminobutyric acid)

GABAergic neurons are distributed widely GABAergic neurons are distributed widely

in the NS. They are the major source of in the NS. They are the major source of

synaptic inhibition in the NS. synaptic inhibition in the NS.

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GABA (γ-aminobutyric acid)

GAD (glutamic acid GAD (glutamic acid

decarboxylase): decarboxylase):

a good marker of a good marker of

GABAergic neuronsGABAergic neurons

Pyridoxal Pyridoxal

phosphate: VBphosphate: VB66

lack of Black of B66 --- GABA --- GABA

content↓--- loss of content↓--- loss of

synaptic inhibition synaptic inhibition

--- seizures--- seizures

GAD

GABA tansaminase

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GABAGABA receptorsreceptors

Ligand-gated ion channelsLigand-gated ion channels GABAGABAAA and GABA and GABACC: Cl: Cl-- channel channel ↑↑---IPSP ---IPSP

In CNS, GABAIn CNS, GABAAA is the major receptor. is the major receptor.

GABAGABAAA is the target of sedative-hypnotics and is the target of sedative-hypnotics and

antiepileptic drugsantiepileptic drugs

GPCR:GPCR:

GABAGABABB: Gi---AC: Gi---AC↓/↓/KK++↑↑---IPSP---IPSP

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GABAGABAA A receptorreceptor

Five subunits: Five subunits: αβγαβγare are

absolutely necessary absolutely necessary

(2(2αα22βγβγ))

GABA: GABA: ββ subunit subunit

Agonist: Muscimol Agonist: Muscimol

（蝇蕈醇）（蝇蕈醇） Antagonist: Bicuculline Antagonist: Bicuculline

（荷包牡丹碱）（荷包牡丹碱）

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GABAGABAA A receptorreceptor Benzodiazepine: Benzodiazepine: αα subunit subunit

Sedative-hypnotics Sedative-hypnotics （镇静催眠药）（镇静催眠药）

Agonist: diazepam Agonist: diazepam （地西泮）安定（地西泮）安定

Inverse agonist: Inverse agonist: ββ-carboline -carboline （卡波（卡波

林）林）

Antagonist: flumazenil Antagonist: flumazenil （（氟马西尼）氟马西尼）

Barbiturate: antiepileptic drugs Barbiturate: antiepileptic drugs （（抗癫痫抗癫痫

药）药） and anaesthesiaand anaesthesia （麻醉）（麻醉）

Neurosteroids: as barbiturateNeurosteroids: as barbiturate

Picrotoxin: antagonist Picrotoxin: antagonist

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GlycineGlycine

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GlycineGlycine

Glycine is the major NT in interneurons at spinal cord Glycine is the major NT in interneurons at spinal cord

(Renshaw cell)(Renshaw cell)

Serine hydroxymethyltransferase: Serine hydroxymethyltransferase:

Mutations---hyperglycinemia (a devastating neonatal disease)--- Mutations---hyperglycinemia (a devastating neonatal disease)---

lethargylethargy （嗜睡）（嗜睡） seizuresseizures （抽搐）（抽搐） and mental retardationand mental retardation （智力（智力低下）低下）

Co-agonist for NMDA receptorCo-agonist for NMDA receptor

Glycine receptor: ClGlycine receptor: Cl-- channel 3 channel 3αα22ββ

Antagonist: strychinine Antagonist: strychinine （士的宁）（士的宁） ---excited effect or ---excited effect or

eclampsiaeclampsia

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NeuropeptideNeuropeptide

Pre-propeptidePre-propeptide

PropeptidePropeptide

Active peptideActive peptide

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Differentia between classical transmitters Differentia between classical transmitters and neuropeptidesand neuropeptides

classical classical transmitterstransmitters

neuropeptidesneuropeptides

MolecularMolecular smallsmall largelarge

SynthesisSynthesis axon terminalaxon terminal propeptide cleavepropeptide cleave

StorageStorage small clear-coresmall clear-core large dense-corelarge dense-core

TerminationTermination reuptakereuptake enzymatic enzymatic degradationdegradation

EffectEffect fast and accuratefast and accurate slow and longslow and long

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Neuropeptide

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Opioid peptidesOpioid peptides

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POMC: Proopiomelanocortin( 阿黑皮原）

Proenkephalin（脑啡肽原）

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Opioid receptorOpioid receptor

GPCR: GPCR:

μμ: : ββ-EP (midbrain and thalamus) -EP (midbrain and thalamus)

κκ: Dyn A and Dyn B: Dyn A and Dyn B

δδ: L-ENK and : L-ENK and ββ-EP -EP

Agonist: Morphine(Agonist: Morphine( 吗啡吗啡 ) Codeine() Codeine( 可待因）可待因）

Antagonist: Naloxone (Antagonist: Naloxone ( 纳洛酮）纳洛酮）

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NONO

Robert F. Furchgott Louis J. Ignarro Ferid Murad

1998: Nobel prize for Physiology or Medicine

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Differentia between classical transmitters and NODifferentia between classical transmitters and NO

NONO Classical transmittersClassical transmitters

SynthesisSynthesis enzymatic promotionenzymatic promotion enzymatic promotionenzymatic promotion

StorageStorage no vesicleno vesicle vesiclevesicle

ReleaseRelease diffusediffuse exocytosisexocytosis

TerminationTermination diffusediffuse enzymatic degradation enzymatic degradation or reuptakeor reuptake

ReceptorReceptor effect enzymeeffect enzyme receptorreceptor

Effecting siteEffecting site extensiveextensive mainly at synapsemainly at synapse

DirectionDirection bidirectionalbidirectional unidirectionalunidirectional

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Synthesis, release, and termination of NO

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NONO

eNOS: Smooth muscle relaxation;eNOS: Smooth muscle relaxation;

nNOS: Involved in 1) memory and learning; nNOS: Involved in 1) memory and learning;

2)regulation of neurotransmitter release.2)regulation of neurotransmitter release.

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EmphasesEmphases


AchAch 、、 NENE

5-HT SSRI5-HT SSRI


GABAGABAAA receptor receptor

Differentia between classical transmitters and Differentia between classical transmitters and

neuropeptides neuropeptides

NO signal pathwayNO signal pathway

1 Neurotransmitter Su Bo Institute of neurobiology 0531-88382329; [email protected].

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Transcript of 1 Neurotransmitter Su Bo Institute of neurobiology 0531-88382329; [email protected].