GABA, Glutamate and their receptors Flashcards Preview

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Flashcards in GABA, Glutamate and their receptors Deck (38):
0

what are ionotropic receptors?

ligand gated ion channels
rapid response
depolarise or hyperpolarise the post synaptic cell- depends on receptor type and ionic gradient

1

what are metabotropic receptors ?

coupled to G protein - open or close ion channels via intermediaries
slower response
transduce signal to the cell interior - indirectly activate ion channels on the plasma membrane through signalling cascade which involved G proteins

2

what is glutamate ?

most abundant excitatory neurotransmitter in the vertebrae nervous system

3

what is GABA?

most abundant inhibitory neurotransmitter in the vertebrate nervous system

4

when glutamate and is present in the synaptic cleft where does it go to be removed ?

enters glial cells or astrocytes or presynaptic terminal

5

what enzyme converts glutamate to glutamine ?

glutamine synthetase
glutamine can be taken from glial cells into neurons

6

if too much glutamate is present what can it cause ?

excitotoxicity
it can be highly toxic

a low concentration of glutamate applied to neurons in culture kills the cells

7

what was discovered in the 1970s about glutamate ?

glutamate given orally produces neurodegeneration in vivo
- this caused considerable alarm because of the widespread use of glutamate as a taste enhancing food additive MSG

8

what is excitotoxcity associate with ?

activation of NMDA receptors
- results mainly from a sustained rise in intracellular calcium concentration
- there are mechanism that act normally to protect neurones- calcium transport system

9

what are the glutamate receptors like ?

metabotropic ones - mGluRs 1-8
- slow and modulatory

ionotropic ones
- AMPA, Kainate and NMDA - receptors are named after the agonists that bind to them with high specificity
- fast synaptic transmission

10

what are the subunits of NMDA receptors ?

NR1
NR2A, B, C and D
NR3A and B

11

what are the subunits of AMPA receptors?

GluR1
GluR2
GluR3
GluR4

12

what are the subunits of Kainate receptors ?

GluR5
GluR6
GluR7
KA1
KA2

13

what are the classes of metabotropic glutamate receptors ?

class1 - mGluR1 and mGluR5
class2- mGluR2 and mGluR3
class 3 - mGluR4, mGluR6, mGluR7 and mGluR8

14

what effects does activation of class 1 glutamate receptors have ?

stimulates phospholipase c
PIP2 is cleaved into DAG and IP3

they are activated by trans-ACPD and quisqualate

15

what happens when class 2 glutamate metabotropic receptors are activated ?

inhibit adenylyl cyclase
activated by trans-ACPD and quisqualate

16

what happens when the class 3 glutamate metabotropic receptors are activated ?

inhibit adenylyl cyclase
activated by L-AP4 and L-SOP
no effect caused by trans-ACPD and quisqualte so they can be differentiated from the class 2 receptors
act ass autoreceptors

17

what is the obligatory subunit of NMDA receptors ?

NR1
if its not present then the channel cannot function

18

what binds to the NR1 subunit of NMDA receptors ?

glycine
it doesnt actually activate the channel because it is a co agonist however it causes greater activation when glutamate binds

19

what is PCP and what does it bind to ?

angel dust
binds to NMDA receptors

20

what are the rules of assembly of AMPA receptors ?

- homomultimers= 2 or more identical components
- heteromultimers= 2 or more different components

21

what are the rules of assembly of kainate receptors ?

GluR 5, 6 and 7 are homomultimers
heteromultimers

22

what are the rules of assembly of NMDA receptors ?

heteromultimers
NR1 must partner 1 or more NR2 subunits
assemble as hetero-tetramers of 2 obligatory NR1 subunits and 2 regionally localissed NR2 subunits

23

what are the modulatory sites of NMDA receptors ?

glycine binding sites
polyamine antagonist site
Mg 2+ block
channel blocking drugs

24

what drugs target glutamate receptors ?

ketamine
PCP
AMPAkines

25

what percentage of synapses does GABA localise to ?

30%

26

what drugs are GABAa receptors sensitive and insensitive to and what are the effects of its activation ?

sensitive to BICUCULLINE
insensitive to BACLOFEN
activation causes chloride influx to hyperpolarize the cell

27

what drugs are GABAb receptors sensitive and insensitive to and what are the consequences of its activation ?

sensitive to BACLOFEN
insensitive to BICUCULLINE
modulates neurotransmitter release via potassium ad calcium channels

28

where is the GABA binding site in GABAa receptors?

between the alpha and beta subunits

29

where is the benzodiazepine binding site in the GABAa receptors ?

between the alpha and gamma subunits

30

where is the alpha 1 subunit of GABAa receptors present ?

widely distributed throughout brain

31

where are the alpha2 subunits of GABAa receptors present ?

mainly present in the hippocampus

32

where are alpha 3 subunits of GABAa receptors present ?

mostly in the cortex- none in the cerebellum

33

where are the alpha 4 subunits of the GABAa receptors present ?

some in the hippocampus
low level expression throughout the brain

34

where are the alpha 5 subunits of the GABAa receptors present ?

present in CA1 and CA3 regions in the hippocampus

35

where are the alpha 6 subunits of the GABAa receptors present ?

100% in cerebellum - not present anywhere else

36

what effect does GABA subunit composition have ?

it determines the intrinsic properties of the channel- affinity, kinetics, conductance, allosteric modulation, probability of channel opening, interaction with modulatory proteins and subcellular distribution

37

what is the typical in vivo subunit composition of GABAa receptors ?

2 alpha, 2 beta and one gamma or delta subunit