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year three exam 2 > neurotransmitters > Flashcards

neurotransmitters Flashcards

1
Q

what is glutamate

A

an amino acid that can be synthesised in all cells - metabolic glutamate and transmissible glutamate

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2
Q

how is glutamate synthesised

A

from glucose via TCA and GABA-T in krebs cycle
from glutamine by glutaminase

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3
Q

how is glutamate processed and released from cells

A
  1. glutamate made in neuron
  2. loaded into synaptic vesicle via V-GLUT
  3. on Ca2+ influx, synaptic vesicle releases glutamate into synapse
  4. glutamate is taken up into astrocyte or neuron via EAAT
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4
Q

what are the two types of glutamate receptors

A

metabotropic glutamate receptors - mGluRs - GPCR
ionotropic glutamate receptors - ligand gated ion channels

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5
Q

what are mGluRs

A

GPCRs belonging to C class with large extracellular N-terminal where glutamate binds
8 subtypes mGluR1-8 split into three groups

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6
Q

what are the three mGluR groups

A

group 1 - mGluR1 and 5
- post synaptic and excitatory
- G alpha Q/11 - increases calcium
group 2/3 - mGluR 2/3 (2) mGluR 4-7 (3)
- presynaptic neuromodulation inhibitors
- G alpha i/o - decreases cAMP

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7
Q

what are the three classes of ionotropic glutamate receptors

A

NMDA
AMPA
Kainite
- all respond to different synthetic glutamate analogues
- all have similar structures - tetramers

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8
Q

what are NMDAR

A
  • receptors that only respond to Lglutamate and NMDA
  • tetrameric that forms a hetero-tetramer of 7 potential subunits
  • usually 2GluN1 and 2GluN2
  • receptor composition affects properties of receptor
  • selective for Na, Ca, K
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9
Q

what are the 5 binding sites present on NMDAR

A
  1. glutamate - agonist site
  2. glycine
  3. polyamine
  4. Mg2+
  5. channel blocking site
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10
Q

how does glutamate bind to NMDAR

A

each tetramer binds to two molecules of glutamate, requires co-agonist of 2 glycine (D-serine or D-alanine) at GluN1

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11
Q

what competitive agonists can act at the glutamate site on NMDAR

A

D-AP5

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12
Q

what antagonists can bind to the glycine site on NMDAR

A

kynurenic acid and CGP 61594

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13
Q

what is the polyamine site on NMDAR

A

modulator site at amino terminal domain - allosteric modulators - can increase responses

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14
Q

what is the Mg2+ side on NMDAR

A

Channel is blocked by Mg 2+ at resting neuronal membrane potentials giving NMDAR voltage dependant channel block

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15
Q

what is the channel blocking site on NMDAR

A

allows for binding when the channel is open - ketamine, memantine

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16
Q

what are AMPAR

A

ligand gated ion channels that only respond to AMPA and L glutamine - forms a homotetramer or mixed heterotetrametric - impermeable to calcium and mediates fast excitatory transmission

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17
Q

what are KAINITER

A

ligand gated ion channels that only respond to kainite and L glutamine - structurally similar to AMPAR

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18
Q

what is end plate potential (EPP)

A

EPP is very large and activates an action potential in the muscle cell which then propagates - type of EPSP

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19
Q

what is EPSP

A

excitatory post synaptic potential

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20
Q

where are EPSPs formed in the CNS

A

pre-synaptic neurons - input from many presynaptic neurons is required to generate an action potential - Depolarisation eventually reaches threshold for firing

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21
Q

what are glutamergic receptors

A

excitatory receptors with round synaptic vesicles and large postsynaptic density

22
Q

what are GABA receptors

A

inhibitory receptors with flattened synaptic vesicles with less postsynaptic density

23
Q

what is post synaptic density

A

Receptors are clustered by lots of regulatory proteins into areas called a postsynaptic density - usually containing AMPAR (fast) and NMDAR (slow)

24
Q

which protein is responsible for clustering receptors

A

PSD-95 - contains PDZ for protein-protein binding - binds directly to NMDAR but binds to TARP to regulate AMPAR

25
Q

what is synaptic plasticity

A

long term changes in connectivity between neurons - Long term potentiation (LTP) is a form of synaptic plasticity

26
Q

what is long term potentiation

A
  • Postsynaptic AMPA receptors are activated but NMDAR requires a sustained depolarisation to relieve Mg2+ block
    • Ca2+ entry can activate other enzymes including kinases (PKC, CaMKII) which phosphorylate AMPAR increasing responses
    • Phosphorylation increases AMPAR conductance and can increase expression
27
Q

what is excitotoxicity

A

High calcium permeability of NMDAR can cause problems - lots of glutamate = lots of calcium = neuronal cell death

28
Q

what is GABA

A

main inhibitory neurotransmitter in the brain - widespread and ubiquitous

29
Q

how is GABA synthesised

A

precursor is glucose - formed from glutamate by GAD

30
Q

how is GABA metabolised

A

by GABA-T

31
Q

how is GABA stored

A

synthesis in GABA-ergic nerve terminals and packaged into vesicles and recycled from synapse by GAT or astrocytes via GAT3

32
Q

what is a drug example of a GABA reuptake inhibitor

A

guvacine

33
Q

what are the two types of GABA receptors

A

ionotropic ligand gated channels
metabotropic receptors

34
Q

what are ionotropic ligand gated channels

A

GABAa - post synaptic receptor to mediate fast inhibition via Cl- (influx causes hyperpolarisation and reduces excitability)

35
Q

what are the 5 drug binding sites on GABAa

A

receptor site GABA
benzodiazepine site
modulatory site - barbituates
neurosteroid site
pirotoxin site - channel blocking

36
Q

what is the receptor site on GABAa

A

agonist site, opens ion channel, 2 sites per pentamer

37
Q

what is the benzodiazepine site on GABAa

A

selectively enhances the effects of GABA - at alpha gamma subunit interface

38
Q

what is the modulatory site on GABAa

A

increases ligand binding to benzo and receptor site to give stronger response - barbiturates

39
Q

what is the Neurosteroid site on GABAa

A

endogenous modulators that enhance effects of GABA

40
Q

what is the pirotoxin site on GABAa

A

within the ion channel pore and requires opening - no use- convulsions

41
Q

what is a GABA metabotropic receptor

A

GABAb - couples through g alpha i/o - inhibits calcium voltage channels and reduces neurotransmitter release from presynaptic terminals

42
Q

what is glycine

A

inhibitory neurotransmitter in the CNS - co-agonist at NMDA, glycine receptor is similar to GABAa

43
Q

what is the role of 5-HT

A

CNS neurotransmitter, found in the gut and involved in platelet aggregation

44
Q

how is 5-HT synthesised

A

tryptophan hydroxylated by tryptophan hydroxylase to 5-Hhydroxytryptopan - dopa decarboxylase to 5-HT

45
Q

storage and transport of 5-HT

A

VMAT loads into vesicles
MAO controls degradation
SERT permits reuptake of 5HT

46
Q

functions of 5HT

A

stored and released from serotonergic neurons, similar distribution to noradrenergic neurons - sleep, appetite, mood, pain and thermoregulation

47
Q

what are the 2 types of 5HT receptors

A

13 GPCR
1 ligand gated ion channel

48
Q

what are the 7 names of the 5-HT receptors

A

5HT3 - ion channel
5HT1A-E - G apla i/o
5HT2A-C - G alpha q/qq
5HT4-7- G alpha S

49
Q

what are 5HT1B/D agonists used for

A

triptans - migraines

50
Q

what are 5HT1A partial agonists used for

A

buspirone - anxiety

51
Q

what are 5HT2 antagonists used for

A

migraine prophylaxis - pizotifen

52
Q

what are 5HT3 antagonists used for

A

ondansetron - antiemetic

year three exam 2 (38 decks)

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