neurotransmitters ii (iua, fm, 2012)
TRANSCRIPT
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Neurotransmitters
. . . .
Department of Biochemistry
Faculty of Medicine
International University of Africa.
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Neurotransmittersarechemicalsmessengersthatrelay,amplify andmodulate signalsbetweenaneuronand
anothercell.
Neurotransmitters enablethetransmissionofimpulses
.
4/3/2012 2Dr.AtifHassanKhirelsied
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Neurotransmitters
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Basedontheirchemicalnature,therearethreemajortypes:
1. Aminoacidsandamines.
2. Neuropeptides.
3. Gases.
4/3/2012 4Dr.AtifHassanKhirelsied
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Catecholamines:
Dopamine
Norepinephrine Epinephrine
Serotonin.
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DOPA).
Norepinephrine
p nep r ne
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Catecholaminessynthesis
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.
Producedinseveralareasofthebrain,includingthe
substantia nigra andtheventraltegmental area.
Has five t es of rece tors D D D .
n ravenous n us onpro uces ncrease ear ra e
andbloodpressure..
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TherearefivedifferentDAreceptorsubtypesthatbelongtotwo
1,
2.
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D min
Inactivationanddegradation
Therearetwomajordegradationpathwaysfordopamine.
Inthebrain(striatum,basalganglia),dopamineis
removedbydopaminetransporter(DAT1),thendegraded
bymonoamineoxidase (MAOAandMAOB)into3,4
dihydroxyphenylaceticacid.
Intheprefrontalcortex,itisremovedbynorepinephrinetransporter(NET),thendegradedbycatecholOmethyl
transferase (COMT)into3methoxytyramine.
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Thedegradationofdopamine
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Thedegradationofcatecholamines
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withthedopaminesystem.
Parkinson'sdisease,iscausedbylossof
nigra.
Schizophrenia involveselevatedlevelsof
anddecreasedlevelsofdopamineinthere rontalcortex.
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'
ymp oms:
Motorandcognitiveimpairment. remors
Rigidity
Cause:
egenera ono neurons n esu s an a n gra.
rea men :
Ldopa,DAcannotcrosstheBBB.
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Parkinson'sdisease,iscausedbylossofdopaminesecreting
.
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Allaremetabotropic receptors.
Therearetwobasictypes:
Man dru susedtotreatnon s chiatricconditions
actonadrenergicreceptorsinthePNS.
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epr mary ocat ono nora renerg cneurons nt e
CNSisthelocuscoerulus.
NEisinvolvedin:
Hunger Sex
Fear
Anxiet Pain
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Examplesofdrugsaffecting adrenergicsystem
Drug Action
Phenelzine (antidepressant) Increasecatecholaminesby
inhibitingMAOmethylparatyrosine(AMPT)
(Pheochromocytoma)
Depletescatecholaminesby
inhibitingtyrosinehydroxylase
Reserpine (antipsychotic
and
antihypertensive) Depletescatecholaminesbyinhibitingvesicular uptake
mp e am ne psyc os mu an e easeca ec o am nes
Cocaine s chostimulant Inhibitscatecholaminesreu take
Propranolol (hypertensive) Blocks receptors
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Indolamines
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Theaminoacidtryptophan isaprecursorof
neuro ransm ersero on n w c n urn s e
recursorofhormonemelatonin..
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Biosynthesisofserotonin
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SSRI:Selectiveserotoninreuptake
inhibitors
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Thedegradationofserotonin
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Featuresofthe5HTsynapse
5HTreleasingneuronssharemanyofthesamefeaturesas
Dopamineandnorepinephrine releasingneurons.
Reuptakeoccursviathe5HTtransporter.
BreakdownoccursviaMAO,butnotCOMT.
Thereareatleast15different5HTreceptorsubtypes.
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Doeseatingtryptophanincrease5HTlevels?
Largedosesoftryptophandoincrease5HTlevelsin
uptakeintothebrain).
HighCHOmealsreleaseinsulinwhichstoresamino
aci s, utnottrp,t usincreasingt eamounto trp
availableby14%.
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Theaminoacids
Excitatoryaminoacids:createEPSPS
Glutamate
MainexcitatoryNTinCNS spartate
Inhibitoryaminoacids:createIPSPS Gammaaminobutyric acids(GABA)
MaininhibitoryNTinCNS
yc ne
Normallyinhibitsmotorneuronactivityinspinalcord
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.
Therearetwobroadcategoriesofglutamatereceptors:
1. Ionotro ic rece torsareli and atedionchannels.
2. Metabotropic areGproteincoupledreceptors.
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Glutamaterece tors
inthebrain:1. AMPA: standardionotropicEPSPcreatingreceptor,
.
2. NMDA:special. NormallyblockedbyMg+2
AMPA=(amino3hydroxyl5methyl4isoxazolepropionate)isa
.
NMDA = Nmeth lDas articacid isanaminoacidderivativeactin asa
specificagonistattheNMDAreceptor.
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Glutamatereceptors
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GABAissynthesizedfromGlutamateinonestep.
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GABAisremovedfromthesynapsebytransporter
proteinslocatedinglial cells.
A roximatel 40% of nerve terminals in the cortex
hippocampusandsubstantia nigrauseGABA.
TherearetwoGABAreceptors:
. A: onotrop c
2. GABAB:Metabotropic
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A
Thereceptorisamultimeric receptorthatconsistsoffive
subunitsarrangedaroundacentralpore.
ActivationofGABA receptorsallowsCl toflow(the
chlorideshunt).
Thishyperpolarize therestingpotential,andmakeit
difficultforexcitator NTstode olarizetheneuron.
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TheGABAAReceptor
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A
InadditiontotheGABAbindingsitethereceptorhassites
forexogenousligands.
Benzodiazepines(BDZs)
Barbiturates
Ethanol
TheseligandsincreasedtheeffectofGABAandtypically
haveanxiol tic anticonvulsant amnesic sedativehypnotic,euphorianteffects.
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B
Theyaremetabotropictransmembranereceptorsfor
linkedtoGproteinsandK+
channels.
O en K+ channels and h er olarize the restin
potential
PreventsNa+ channelsopeningandactionpotentials
.
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Neuropeptides
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Neuro e tides:
Neuro e tidesaresmall roteins.
LargerthanotherNTs.
Madeincellbody(soma).
.
CanbereleasedfromsamesynapseasotherNTs.
Donotactuponionchannels
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Solublegases
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Producedincytoplasmbyenzymes.
Diffusefreelyacrossmembranetoneighboringneurons.
Nitrousoxide(NO)
Regulatesvasculartone.
Involvedinlearningandmemory.
Carbonmonoxide(CO)
Regulatesvasculartone. Regulatesperistalsis.