GLUTAMATE GLUTAMATE RECEPTORSRECEPTORS

SUBMITTED BY SUBMITTED BY ÖÖZGE ZGE ŞŞENYURTENYURTMMİİNE NUYANNE NUYANERTAN ERTAN ÖÖZERTAN ZERTAN M. EMRE M. EMRE ÖÖZDEMZDEMİİR R

GlutamateGlutamate is is thethe majormajor excitatoryexcitatoryneurotransmitterneurotransmitter in in thethe mammalianmammalian CNS, CNS, actingacting throughthrough bothboth ligandligand gatedgated ionionchannelschannels ((ionotropicionotropic receptorsreceptors) ) andand GG--protein protein coupledcoupled ((metabotropicmetabotropic) ) receptorsreceptors

GlutamateGlutamate receptorsreceptors playplay a a vitalvital role in role in thethe mediationmediation of of excitatoryexcitatory synapticsynaptictransmissiontransmission

NMDAR1NMDAR2A, ...NMDA-receptor family

Iono

tropi

c re

cept

ors

Met

abot

ropi

c re

cept

ors

GluR1GluR2GluR3…GluR6

AMPA-receptor family

Rec

epto

r sub

unitsKainate-receptor family

Glutamateacts on: mGlu1A

mGlu5AGroup I(Phospholipase C activation)

mGlu2mGlu3

Group II(Adenylyl cyclase inhibition)

mGlu4, mGlu8mGlu6, mGlu6

Group III(Adenylyl cyclase inhibition)

NONNON--NMDA RECEPTORSNMDA RECEPTORS

GiveGive immediateimmediate responseresponse uponupon bindingbinding of of glutamateglutamateMoreMore permeablepermeable toto NaNa++ & K& K+ + thanthan CaCa+ + + +

InfluxInflux of of NaNa++ causescauses depolarizationdepolarization of of thethemembranemembrane whichwhich is is thethe majormajor factorfactor forforactivatingactivating NMDA NMDA typetype receptorsreceptors

NMDA RECEPTORSNMDA RECEPTORS

UnlikeUnlike nonnon NMDA NMDA receptorsreceptors, , theytheyrequirerequire a a coco--agonistagonistGLYCINEGLYCINE

Why ?

OUT

IN

GlycineCo-agonist(activator)

GlutamateNMDA

Wait! You still can’t get through.

Because, as long as the membrane remains polarised, the pore of the channel is blocked by

physiological, extracellular concentration of Mg2+.

Mg2+

Mg2+Mg2+

Mg2+

bindingsite

Ca2+

Na+Ca2+

MetabotropicMetabotropic GlutamateGlutamate ((mGlumGlu) ) ReceptorsReceptors

MetabotropicMetabotropic glutamateglutamate ((mGlumGlu) ) receptorsreceptorsareare GG--protein protein coupledcoupled receptorsreceptors ((GPCRsGPCRs) )

TheyThey areare not not coco--assembledassembled fromfrom multiplemultiplesubunitssubunits, but , but areare oneone polypeptidepolypeptide withwithcommoncommon 7 7 transmembranetransmembrane domaindomain

TheyThey havehave beenbeen subdividedsubdivided intointo threethreegroupsgroups, , basedbased on on sequencesequence similaritysimilarity,,pharmacologypharmacologyintracellularintracellular signallingsignalling mechanismsmechanisms

Metabotropic glutamate receptor groups (from Pin and Duvoisin, 1995).

group mGluR agonist(s) intracellular pathway

I mGluR1, mGluR5

quisqualate, ACPD

increase phospholipase C activity, increase cAMPlevels, increase protein

kinase A activity

II mGluR2, mGluR3

L-CCG-1, ACPD decrease cAMP levels ??

??

III

mGluR4, mGluR6. mGluR7, mGluR8

L-AP4 (APB) decrease cAMP or cGMP levels

REFERENCESREFERENCES

http://www.webvision.med.utah.edu/GLU.hthttp://www.webvision.med.utah.edu/GLU.htmlml

http://www.bris.ac.uk/Depts/Synaptic/info/http://www.bris.ac.uk/Depts/Synaptic/info/glutamate.htmlglutamate.html

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