Block E Lecture 3: Excitatory Amino Acids Neurotransmitters Flashcards
What kind of neurotransmitter is glutamate?
An excitatory neurotransmitter
(Slide 4)
What are 3 example of glutamate receptor agonists?
Quisqualate, Kainate and NMDA
(Slide 4)
What are the 5 subtypes of glutamate receptors?
NMDA
Kainate
AMPA
Delta
GPCR (metabotropic)
(Slide 5)
What agonists act on each of the 5 glutamate
receptor subtypes?
NMDA -> NMDA
Kainate > Kainate
Quisqualate acts on AMPA receptors and the GPCRs
Delta receptors are not traditionally ligand-gated
(Slide 5)
What is the structure of the GPCR glutamate receptor?
They usually function as homodimers, each of its subunits have 7 membrane-spanning (Transmembrane) domains, similar to muscarinic and adrenoceptor receptors
8 different subunits which only pair with other subunits which are the same to form a receptor
(Slide 6)
How were the 8 variants of the glutamate GPCR identified and what are they called?
They were identified by molecular biology and are labelled mGlu1-mGlu8
(Slide 6)
What 3 groups are the 8 glutamate GPCR variants divided into what is the division based on?
Groups are based on molecular biology, coupling, effector mechanisms and pharmacology
Group 1: mGlu1 and mGlu5
Group 2: mGlu2 and mGlu3
Group 3: mGlu4,6,7 and 8
(Slide 9)
What is the coupling, effector mechanisms and 2nd messengers used by groups 1,2 and 3 of the glutamate GPCR variants?
Group 1 uses Gq/11 coupling whereas groups 2 and 3 use Gi/o coupling
Group 1 uses an increase in PLC as an effector mechanism whereas groups 2 and 3 use a decrease in adenylate cyclase (AC)
Group 1 uses an increase of IP3 and DAG as second messengers whereas groups 2 and 3 use a decrease in cAMP levels
(Slide 10)
Where are group I of GPCR glutamate receptors usually located?
On postsynaptic neuron membranes
(Slide 12)
What 3 cellular responses does the activation of group I of GPCR glutamate receptors lead to?
An increase in Na+ and K+ ion conductance (aka excitation)
An increase in inhibitory postsynaptic potential (inhibition)
A modulation of voltage-dependent Ca2+ channels
(Slide 12)
Where are group II and III of GPCR glutamate receptors usually located?
On presynaptic neuron membranes
(Slide 12)
What cellular responses do group II and III of GPCR glutamate receptors lead to?
An increased presynaptic inhibition
Reduced activity of postsynaptic potentials (both excitatory and inhibitory)
(Slide 12)
How do the different GPCR glutamate receptor groups modulate NMDA receptor activity?
Group I increases activity whereas groups II and III decrease it
(Slide 13)
Other than modulating NDMA receptor activity, what are 2 other functional roles that GPCR glutamate receptors have?
Synaptic plasticity: They participate in long-term potentiation and depression
They control the hypothalamic-pituitary-adrenal axis via regulation of cortisol levels and stress responses
(Slide 13)
What are the structure of the ionotropic glutamate receptors?
They are integral cation channels, and are each composed of 4 subunits, which each receptor class having multiple subunits
(Slide 15)
How does the isotropic glutamate receptor subunit structure differ to that of e.g nicotinic?
The TM2 domain is inserted into the cell membrane, but it doesn’t cross it which leads to the N- and C- terminals being on opposites sides of the cell membrane
(Slide 16)
How were the 4 major classes of isotopic glutamate defied?
By their responses to selective agonists
(Slide 17)
What are 3 examples of AMPA receptor agonists?
Glutamate
AMPA
Quisqualate
(S)-5-fluorowillardine
(Slide 18)
State a AMPA receptor antagonist.
NBQX
Tezampanel
(Slide 18)
What are 2 examples of AMPA receptor ligand ion channel blockers?
Polyamines, argiotoxin, jorotoxin and Mg2+ ions (only some subtypes)
(Slide 18)
What is the function of AMPA receptors and how does it do this?
Fast, excitatory synaptic transmission which is enabled due to their ability to move cations across the cell membrane and cause depolarisation
(Slide 19)
What are 3 examples of kainate receptor agonists?
Glutamate
Kainate
ATPA
(S)-5-iodowillardine
Dysiherbaine
(Slide 20)
What is an example of a kainate receptor antagonist?
2,4-epi-neodysiherbaine
(Slide 20)
What is an example of a kainate receptor ion channel blocker?
Polyamines and Mg2+ ions (only some subtypes)
(Slide 20)
