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Ageing > Dopamine And ACh > Flashcards

Dopamine And ACh Flashcards

1
Q

Which three main nuclei in the brain contains the acetylcholine cell bodies?

A
  • Nucleus basalis
  • Septal hippocamptal pathway
  • Substantia nigra
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2
Q

How is acetylcholine made?

A

From choline in the diet and Aceyl-CoA from the Krebs cycle

Combined by acetyltransferase

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3
Q

How is acetylcholine stored?

A

Packaged into vesicles via vesicular ACh transporter which exchanges 2 x H+ for one molecule of ACh

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4
Q

How is acetylcholine released from it’s vesicle into the synaptic cleft?

A

Ca influx which is required for movement of the vesicle and docking to the pre-synaptic terminal

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5
Q

What are the three different types of ACh vesicles?

A
  1. Readily releasable
  2. Recycling phase
  3. Reserve
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6
Q

Which 5 ligand gated nicotinic ion channels does ACh act on?

A

Muscle nAChRs mature (alpha1)2 + beta1 + delta + e
Embryonic muscle (alpha1)2 + beta1 + delta + gamma
Neuronal nAChRs ganglion (alpha3)2 + (beta4)3
Neuronal nAChRs CNS (alpha4)2 + (beta2)3
Neuronal nAChRs CNS (alpha7)5

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7
Q

Which G-protein coupled muscarinic receptors do ACh work on?

A 
M1 - Gq and GII
M2 - Go and Gi
M3 - Gq and GII
M4 - Go and Gi
M5 - Gq and GII
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8
Q

What are the two nicotinic ACh receptors?

A

Four transmembrane domain and ACh binding site
Heteropentomer - 2 x alpha 4, 3 x beta2
Homopentomer - 5 x alpha 7

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9
Q

What is the structure of the muscarinic ACh receptor?

A

7 transmembrane domains
Binding site for ACh found deep in the transmembrane protein
Hydrophilic binding pocket

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10
Q

How does ACh degradation for reuptake occur?

A

Has to be broken down to Choline and Acetic acid by acetylcholinesterases

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11
Q

Which drugs work on the nicotinic ACh receptors?

A

Full agonists - suxamethonium, nicotine
Partial agonists - Varenacline
Reversible antagonists - pancronium, vercuronium
Irreversible antagonists - alpha-bungarotoxin

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12
Q

Which drugs work on the muscarinic ACh receptors?

A

Full agonists - ACh, muscarine, oxotremorine M
Partial agonists - McN-A-343
Reversible antagonists - atropine, ipratropium, benztropine, procyclidine (CNS active)

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13
Q

Which drugs works on the reuptake mechanism of ACh?

A

Hemicholinium

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14
Q

Which drug works on the degradation pathway of ACh?

A

Rivastigmine, neostigmine, galatamine

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15
Q

Which recreational drugs work on the Acetylcholine pathway?

A

Nicotine
Scopolamine
Henbane

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16
Q

Which diseases can be treated with manipulation of the acetylcholine pathway?

A 
Dementia
Myasthenia gravis
Parkinson’s 
Motion sickness
Analgesia
17
Q

Which four localised nuclei is Dopamine found in?

A
  • Substantia nigra
  • Tubero-hypophyseal pathway
  • Mesolimbic pathway
  • Mesocortical pathway
18
Q

How is dopamine synthesised?

A

Tyrosine from the diet is converted to DOPA by tyrosine hydroxylase. DOPA is converted to dopamine by dopa carboxylase

19
Q

How is dopamine stored?

A

In vesicles via vesicular monoamine transporter (VMAT1 + 2)

In exchange for 2 x H+

20
Q

How is dopamine released from the vesicle?

A

Ca dependent

21
Q

What does en passant varicosities mean?

A

Release of dopamine isn’t just at the end terminus but also through varicosities down the axon

22
Q

Which receptors does dopamine act on?

A

D1-like: D1, D5 coupled to Gs

D2-like: D2, 3, 4 coupled to Gi

23
Q

What is the structure of the dopamine receptors?

A

7 transmembrane units
Dopamine binding site deep within the hydrophilic pocket inside the membrane protein
Third intracellular loop region dictates which G protein it is coupled to

24
Q

How does reuptake of dopamine occur?

A

Via DAT - dopamine active transporter

Goes back into the cell for reuse

25
Q

What is the end product of dopamine degradation?

A

Homovanillic acid via either COMT or MAO

26
Q

Which drugs works on the synthesis of dopamine?

A

Levo-DOPA

27
Q

Which drugs work on the storage of dopamine?

A

Reserpine and methamphetamine

28
Q

Which drugs work on the release of dopamine?

A

Amantadine

29
Q

Which drugs are full agonists at the dopamine receptors?

A

Dopamine
Apomorphine
Bromocriptine

30
Q

Which drugs are antagonists at the dopamine receptor?

A

Haloperidol

Chlorpromazine

31
Q

Which drugs work at the reuptake system of dopamine?

A

Cocaine
Bupropion
Methylphenidate

32
Q

Which drugs work at the degradation stage of dopamine?

A

MAO inhibitors

COMT inhibitors - entacapone, tolcapone

33
Q

Which two recreational drugs work on the dopamine pathway?

A

Cocaine

Amphetamines

34
Q

Which diseases can be treated via manipulation of the dopamine pathway?

A 
Drug dependence
Parkinson’s disease
Schizophrenia
Nausea/vomiting
Hormonal imbalances

Ageing (3 decks)

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