neurotransmitters ii (iua, fm, 2012)

8/2/2019 Neurotransmitters II (IUA, FM, 2012)

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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.

neurotransmitters ii (iua, fm, 2012)

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