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Aging > Neurotransmitter > Flashcards

Neurotransmitter Flashcards

1
Q

What is glutamate

A

Amino acid, widely distributed in the CNS, very little in the PNS.
Most important excitatory NT in the CNS

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2
Q

What is the glutamate cycle in a neurone

A

glutamine is taken and glutaminase converts it to glutamate. Transaminase then converts glutamate to alpha-oxoglutarate.

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3
Q

What is the glutamate cycle in a glia

A

glutamate is made from alpha-oxoglutarate by GABA transaminase. Glutamate is then converted into glutamine by glutamine synthase

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4
Q

Where is glutamate stored

A

Vesicles (20mM concentration)

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5
Q

How is glutamate transported

A

Transported in by vesicular glutamate transporter (vGlut), from cytosol into vesicle. Uses protons (2H+) as a concentration gradient. Difference in hydrogen ions is formed from proton pump (uses ATP).

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6
Q

How is glutamate released

A

Calcium dependent vesicular release - axon end terminal bouton

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7
Q

What are the ionotropic receptors for glutatmate

A

iGluR (ion channels activated by glutamate)
NMDA cation channel Na+, K+, Ca2+
AMPA cation Channel Na+, K+ (some Ca2+)
Kainate cation channel Na+, K+
Each subunit has 3 transmembrane units and a P loop. Glutamate binds on N terminal. Needs 4 subunits for one receptor.

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8
Q

What are the metabotropic receptors for glutamate

A

mGluR (G-protein coupled receptors, class C)
Group I - mGLuR1 & mGLuR5 couple to Gq and G11 G proteins
Group II - mGluR2 & mGluR3 couple to Go (most common in the nervous system) and Gi G proteins
Group III - mGluR4 & mGluR6-8 couple to Go and Gi G proteins
7 transmembrane domains. Glutamate binds on N terminus. Intracellular area couples to G proteins.

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9
Q

How does glutamate reuptake occur

A

Glutamate can bind to receptor
Can disappear in bloodstream
Reuptake by excitatory amino acid transporters (AA) - requires cotransport for Na+, H+ and K+. Can be recycled into vesicles straight away. Or via astrocytes: glutamateíglutamine by glutamine synthase and then transported back into the neurone via glutamine transporters. Glutamine is converted to glutamate by glutaminase.

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10
Q

What are NMDA receptor drugs

A

ketamine (channel blocker), memantine (competitive antagonist for Alzheimer’, phencyclidine

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11
Q

What are AMPA receptor drugs

A

perampanel (competitive antagonist for epilepsy)

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12
Q

What is GABA

A

Amino acid, widely distributed in the CNS, very little in the PNS, most important inhibitory NT in the CNS

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13
Q

How is GABA synthesised

A

glutamate by GAD (glutamic acid decarboxylase)

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14
Q

Where is GABA stored

A

Stored in vesicles by vGABAT. Pumped in by hydrogen ions, which is activated by ATP activated proton pump.

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15
Q

How is GABA released

A

Calcium dependent vesicular release, axon end terminal bouton

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16
Q

What are the ionotropic GABA receptors

A

GABAa receptor - anion channel Cl-

4 transmembrane units. Needs 5 subunits. Has binding site for benzodiazepines.

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17
Q

What are the metabotropic GABA receptors

A

GABAb receptor couple to Gi and Go G proteins.

7 transmembrane units.

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18
Q

How is GABA transproted

A

GAT1: neuronal GABA transporter
GAT3: glial GABA transporter

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19
Q

How does GABA reuptake occur

A

Alpha-oxoglutarate converted to glutamate by GABA transaminase
GABA converted to succinic semialdehyde by GABA transaminase
This mostly occurs in glia

20
Q

What are GABAa drugs

A

muscimol (agonist), bicuculline (competitive antagonist), picrotoxin (channel blocker), benzodiazepines, ethanol and some general anaesthetics are all positive allosteric modulators

21
Q

What are GABAb drugs

A

baclofen (agonist), saclofen (competitive antagonist)
Reuptake: tiagabine (blocks GAT)
Degradation: vigabatrine (blocks GABA-t)

22
Q

What is acetylcholine

A

Lower motor neurones, GI tract, preganglionic autonomic nerves, post ganglion parasympathetic, retina
Usually long distance neurones or striatal interneurons

23
Q

How is Ach synthesised

A

Synthesised from choline and acetyl-CoA with choline acetyltransferase (ChAT). Occurs in the nerve terminal. ChaT synthesised in the cell body and transported to the terminals

24
Q

How is Ach stored

A

Stored in vesicles (up to 100 mM, compared to cytosol concentration of 1mM). Exchanged with hydrogen ions with vesicular acetylcholine transporter.

25
Q

How is Ach released

A

Calcium dependent vesicular release. End terminal. Vesicular pools: releasable, recycling and reserve

26
Q

What are nicotinic receptors for Ach

A

Ligand gated ion channels nicotinic (pentameric):

4 transmembrane domains with 5 subunits to produce functional channel

27
Q

What are muscarinic receptors for Ach

A

GPCRs (class A, rhodopsin type), muscarinic:
M1 - Gq/GII
M2 - Go/Gi
M3 - Go/GII
M4 - Go/Gi
M5 - Gq/GII
7 transmembrane domains. Binding for acetylcholine in the transmembrane domain

28
Q

How does Ach reuptake ocur

A

Choline transporter for reuptake (Ach must be degraded to choline before it can be reuptaken)

Acetylcholinesterase breaks acetylcholine into choline and acetic acid. Mostly located in the synaptic cleft (extracellular)

29
Q

What are the drugs for Ach storage

A

vesamicol (blocks transporter)

30
Q

What are the drugs for Ach release

A

Botulinus toxin

31
Q

What are the drugs for nAch receptor

A

Full agonists - suxamethonium, nicotine
Partial - varenacline (stops smoking, but does not give withdrawal symptoms)
Reversible antagonist - pancronium, vercuornium
Irreversible antagonist - alpha-bungarotoxin

32
Q

What are the drugs for mAch receptor

A

Full agonists - muscarine, oxotremorine M
Partial agonist - McN-A-343
Reversible antagonsits - atropine, ipratropium, benzotropine, procyclidine (CNS active

33
Q

What are the reuptake drugs for Ach

A

hemicholinium

34
Q

What are the degradation drugs for Ach

A

endophonium, neostigmine, physostigmine, galantamine, rivastigmine

35
Q

What is dopamine

A

Monoamine
Location in location (e.g. nigrostriatal pathway, tubero-hypophyseal pathway, mesocortical pathway (overactive in schizophrenia), mesolimbic pathway)

36
Q

How is dopamine synthesised

A

Tyrosine->Dopa with tyrosine hydroxylase

Dopa->Dopamine with dopa decarboxylase

37
Q

How is dopamine stored

A

Storage with VMAT (vesicular monoamine transporter) - 1 or 2 can be cell type specific. Exchange for 2 hydrogen ions

38
Q

How is dopamine released

A

Calcium dependent vesicular release
End terminal
En passant varicosities

39
Q

What are dopamine receptors

A

All GPCRs (class A, rhodopsin-like)

DI-like: D1, D5 coupled to Gs
D2-like: D2, D3, D4 coupled to Gi

7 transmembrane domain, with binding inside the transmembrane domain

40
Q

How does dopamine reuptake occur

A

dopamine active transporter (DAT), requiring CL- and 2 Na+

41
Q

How does dopamine degradation occur

A

output is homovanillic acid (ideally in CSF or urine)

Two main enzymes are MAO and COMT

42
Q

What are dopamine receptor drugs

A

Full agonists - DA, apomorphine, bromocriptine
Antagonists - haloperidol, chlorpromazine (anti-schizophrenic)
Reuptake: cocaine, bupropion, methylpenidate (Ritaline)

43
Q

What are dopamine synthesis drugs

A

L-dopa

44
Q

What are dopamine release drugs

A

amantadine

45
Q

What are dopamine storage drugs

A

Reserpine, methamphetamine

46
Q

What are MAO inhbitiors

A

phenelzine (anti-depressant), selegiline (MAO-B)

47
Q

What are COMT inhibitors

A

entacapone, tolcapone

Aging (8 decks)

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