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Ageing block > Acetylcholine & dopamine > Flashcards

Acetylcholine & dopamine Flashcards

1
Q

What are striatal interneurons

A
  • Present in the striatum (the largest component of the basal ganglia)
  • Cholinergic
  • Important involvement in the alterations in activity
  • associated with PD
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2
Q

How is ach synthesised?

A

Choline( diet& recycled) + Acetyl-coA(krebs cycle) together make ach

  • using the enzyme choline acetyltransferase ( ChaT)
  • Occurs in the nerve terminal
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3
Q

Where is ChaT synthesised

A

-Synthesised in the cell body and transported to the terminals

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4
Q

Where is ach stored

A
  • In vesicles

- Vesicular acetylcholine transporter –> This bring in 1 ach molecule for 2h+

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5
Q

Describe the release of ach

A

-Calcium dependent vesicular release
-End terminal
Vesicular pools: releasable, recycling & reserve

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6
Q

Outline the different receptors that ach can act on

A
  1. ) Ligand gated ion channel nicotinic (pentameric)
  2. ) GPCRs (class A, rhodopsin type), muscarinic
    - M1- Gq/GII
    - M2-Go/Gi
    - M3-Gq/GII
    - M4-Go/Gi
    - M5-Gq/GII
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7
Q

Describe the receptor structures for the receptors that ach can act on

A
  1. ) nAchR (ionotropic)
    - 4TMS
  2. ) mAChR
    - 7TMS
    - ach binding site is deep within the TMS so it forms a hydrophilic binding pocket within the protein
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8
Q

What is the difference between ligand gated receptors and GPCRs

A

GPCRs= slower

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9
Q

Outline the reuptake of ach

A

-Choline transporter ( not ach must be degraded to choline before it can be reuptaken-this is unusual for a neurotransmitter)

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10
Q

Outline the degradation of ach

A

ach is broken down to choline & acetic acid

  • Using the enzyme acetylcholinesterase
  • Mostly located in the synpatic cleft ( extracellular)
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11
Q

Outline the difference between nicotinic and muscarinic receptors

A
  • One uses Ions (Nicotinic) and one uses G-Proteins (Muscarinic).
  • Nicotinic receptors are all excitatory, while Muscarinic receptors can be both excitatory and inhibitory depending on the subtype
  • The nicotinic receptor is a channel protein that, upon binding by acetylcholine, opens to allow diffusion of cations. The muscarinic receptor, on the other hand, is a membrane protein; upon stimulation by neurotransmitter, it causes the opening of ion channels indirectly, through a second messenger.
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12
Q

Outline the drugs that work at the point of storage of ach

A

Vesamicol( stops the vesicular transporter)

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13
Q

Outline the drugs that work at the point of release of ach

A

Botulinus toxin

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14
Q

Outline the drugs that work at the point of nACh receptors of ach

A
  1. ) Full agonists ACh- suxametonium, nicotine
  2. ) Partial agonists-Varenacline aka champix- a nicotinic addiction drug, given to smokers cos it works selectively on your alpha2Beta2 nicotinic receptors in your brain so has very little effect on your nicotinic receptors in your muscles
  3. ) Reversible antagonists-pancronium, vercuronium(NMJ)
    4) Irreversible antagonist- alpha-bungarotoxin
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15
Q

Why are partial agonists good at treating drug addictions

A

-They will act on the receptors to some degree so that they stop any withdrawal problems but they will inhibit the action of the full agonist because they are occupying a number of the ach receptors

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16
Q

Outline the drugs that work at the point of mACh receptors of ach

A
  1. ) Full agonists-ACh, muscarine,oxotremorine M
  2. )Partial agonist McN-A-343
  3. )Reversible antagomists-atropine, ipratropium,benzotropine, procyclidine(CNS active)
17
Q

Outline the drugs that work at the point of reuptake of ach

A

hemicholinium

18
Q

Outline the drugs that work at the point of degradation of ach

A

endophonium,
neostigmine,
physostigmine
galantamine,(crosses the blood brain barrier )
rivastigmine(crosses the blood brain barrier) (CNS active)

19
Q

Outline the recreation drugs associated with ach

A

Nicotine

  • Scopolamine “truth drug”
  • Henbane- helped witches “fly”
20
Q

Outline the diseases associated with problems with ach transmission

A
  • Dementia
  • Myasthenia gravis
  • Parkinson’s
  • Motion sickness
  • Analgesia
21
Q

Outline the characteristics of dopamine

A
  • Monoamine

- Location in CNS

22
Q

What pathway is first affected in PD

A

-Nigostriatal pathway

23
Q

Outline the synthesis of dopamine

A

Tyrosine (diet) is first converted to DOPA using tyrosine hydroxylase(rate limiting)
-DOPA is then converted to DOPAMINE using Dopa decarboxylase

24
Q

Outline the storage of dopamine

A

Vesicular monoamine transporter 1 or 2 can be cell type specific
(VMAT1 or VMAT2 )
-This is a proton ATPase which makes the cell v acidic and transports a dopamine molecule in return for 2 protons

25
Q

Outline the release of dopamine

A
  • Calcium dependent vesicular release
  • end terminal
  • en passant varicosities
26
Q

Outline the receptors that dopamine can act on

A
  • All GPCRs (class A, rhodopsin-like)
  • “D1-like” D1,D5 coupled to Gs
  • “D2 -like” D2,D3,D4 coupled to Gi
27
Q

Outline the reuptake of dopamine

A

Dopamine active transporter(DAT)

  • driving force created by 2Na+ and Cl- ions
  • Dopamine first diffuses to the transporter site
28
Q

Outline the degradation of dopamine

A
  • Degraded using MAO

- COMT(catechol-O-methyltransferase) is also used to convert between structures

29
Q

Outline the drugs that act on the synthesis stage of dopamine

A

Levo DOPA

  • The gold standard for treatment of PD is to add more DOPA
  • Good because it crosses the blood-brain barrier, then gets converted to dopamine in the brain
30
Q

Outline the drugs that act on the storage stage of dopamine

A
  • Reserpine

- Methamphetamine

31
Q

Outline the drugs that act on the release stage of dopamine

A

amantadine

32
Q

Outline the drugs that act on the receptors that dopamine can act on

A
  1. ) Full agonist:
    - DA
    - apomorphine
    - bromocriptine
  2. ) Antagonists:
    - haloperidol
    - chlopromazine
33
Q

Outline the drugs that act on the reuptake of dopamine

A
  • cocaine
  • bupropion
  • methylpenidate(Ritalin)
34
Q

Outline the drugs that act on the degradation of dopamine

A
  • MAO inhibitors-phenelzine,selegiline (MAO-B)
  • COMT inhibitors(prevent the breakdown of levodopa; their main effect is to prolong the duration of action of a dose of levodopa) -entacapone, tolcapone
35
Q

Outline the recreational drugs that affect dopamine

A
  • Cocaine

- Amphetamines “uppers”

36
Q

Outline the disease associated with issues with dopamine transmission (at any stage)

A
  • Drug dependence
  • PD
  • Schizophrenia
  • Nausea/vomiting
  • Hormonal disturbances
37
Q

What is the role of the CTZ( chemoreceptor trigger zone)

A
  • An area of the medulla oblongata that receives inputs from blood-borne drugs or hormones, and communicates with other structures in the vomiting center to initiate vomiting.
  • Dopamine is thought to affect this

Ageing block (16 decks)

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