glutamate receptors - middle east technical...
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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
THANK YOU FOR THANK YOU FOR YOUR ATTENTIONYOUR ATTENTION
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