Session 6 + 7 - Acetylcholine Flashcards Preview

Semester 2 - Membranes and Receptors > Session 6 + 7 - Acetylcholine > Flashcards

Flashcards in Session 6 + 7 - Acetylcholine Deck (43):
1

Where is acetylcholine released in the nervous sytem?

Parasympathetic nervous system
a) Pre ganglionic neurones
b) Post ganglionic neurones
Sympathetic Nervous System
a) Pre ganglion neurones
b) Some post ganglionic neurones (sweat, ejaculation)

2

What is acetylcholine synthesized from and how?

Choline and Acetyl Co-A, via the action of choline acetyltranferase.

3

Where does acetylcholine synthesis take place? What enzyme is produced and how does it get to the nerve terminals?

Acetycholine synthesized in cholnergic neurones.
Choline acetyltransferase made in cell bodies of cholinergic neurones.. Transferred to the nerve terminal by axoplasmic transport.

4

How is acetylcholine packaged for release?

Acetylcholine packed into vesicles and travels to the nerve endings via anteretrograde (movement away from cell body) axoplasmic transport. Stored at nerve ending until action potential arrives.

5

What is the vesicular ACh transporter?

Carrier protein on surface of vesicle in which ACh is absorbed. Actively transport one molecule ACh into vesicle in exchange for two cytoplasmic protons. Example of antiport.

6

How is ACh released from axon terminal?

- Action potential arrives
- Depolarisation causes voltage gates Ca2+ channels to open
- Calcium ions diffuse through down their concentration gradient
- Ca2+ binds to synaptotagmin - a membrane trafficking protein
- Vesicle brought close to membrane
- Snare complex makes a fusion pore
- Transmitter released through pore

7

Give an example of an agent which interferes with ACh release

Botulinum toxin
- Taken into neurones by endocytosis
- Has protease activity, cleaves SNARE complex and prevents neurosecretory vesicle from fusing with nerve synapse.

8

How is acetylcholine degraded?

Acetylcholinesterase
Abundant enzyme which converts acetylcholine into the inactive metabolies choline and acetate

9

What happens to the free Choline and Acetate in the synapse?

Choline - transported back into the neurone by a high affinity choline transporter on the membrane
Acetate- Converted into acetyle CoA and reused to make ACh by choline acetyltransferase

10

List some of the important sites of parasympathetic innervation

Innervation of the heart
Bronchioles
Vasculature
Pupil of the eye
Endocrine glands

11

Wjhat is the effect of increased parasympathetic discharge in the heart?

Decrease heart rate (AVN conduction velocity),

12

Apart from in the parasympathetic system, where else is acetylcholine used in the body?

Preganglioncic in the sympathetic nervouse system
Postganglionic in some part of the sympathetic nervous system, notable to sweat glands (M3)

13

What are two types of acetylcholine receptors?

Nicotinic and mucarinic

14

Why are the two types of acetycholine receptors distinguishable?

Muscarinic receptors more sensitive to muscarine
Nicotinic more responsive to... that's right, you guessed it!
Heroin.

Lol, JK. Nicotine.

15

How do nicotinic acetylcholine receptors cause a post ganglionic response?

- Ligand gated ion channel
- Channel permeable to Na+ and K+, causes depolarisation (local, immediate)
- Action potential propagates

NicotIONe

16

How do muscarinic acetylcholine receptors cause a post ganglionic response?

- G-protein coupled receptor
- G-protein diffuse to membrane protein
- Cascade reaction
- Signal propagated to whole of cell
- Slow response

17

What is the class of acetylcholine receptor found at the neuroeffector junction?

Muscarinic

18

For the following sub type, give the G protein, the effector and whether it is activatory or inhibitory
M1

Gq
Phospholipase C activation, creating IP3 that binds to IP3 receptor

19

For the following sub type, give the G protein, the effector and whether it is activatory or inhibitory
M2

Gi
Inhibits adenylyl cyclase
Opens potassium channels (decreased firing rate action potentials)
Inhibitory

20

For the following sub type, give the G protein, the effector and whether it is activatory or inhibitory
M3

Gq
Activates phospholipase C, creating IP3 that binds to IP3 receptor

21

What is the predominant parasympathetic receptor subtype at the following structures, and give the major physiological action
SA node

M2
Decreased HR

22

What is the predominant parasympathetic receptor subtype at the following structures, and give the major physiological action
Bronchi

M3
Increased bronchoconstriction

23

What is the predominant parasympathetic receptor subtype at the following structures, and give the major physiological action
Bladder

M2 & M3
Contraction causing emptying of the bladder

24

What is the predominant parasympathetic receptor subtype at the following structures, and give the major physiological action
Glands

M3
Increased exocrine and endocrine secretions due to contraction of smooth muscle

25

Parasympathtic nerve terminals at neuroeffector junctions

Acts as a negative feedback mechanism to prevent further ACh release from post synaptic vesicles when ACh conc increases in synapse

26

What is a cholinoceptor agonist?q

Agent which mimics some or all of the actions of acetycholine

27

What is the advantage of synthesizing a cholinoceptor agonist which oly interacts with a particular receptor subtype?

Targeted response can be stimulated

28

What two types of cholinoceptor agonists are available?

Direct = Acts as an analogue to stimulate receptors directly
Indirect - Inhibits acetycholinesterase This prevents the breakdown of Ach and therefore prolongs its activity

29

Give an example of a clinical use of cholinoceptor agonist

Acelidine - M3 agonist
Used in the treatment of glaucoma, by decreasing intraocular pressure

30

What is a cholinoceptor antagonist?

Reduce effects of ACh, can act directly or indirectly with varying levels of selectivity

31

Give an example of Cholinoceptor antagonist and its effects on GI

Dicyclomine
Syptomatic relief of IBS, reduces small bowel symptoms
M1 antagonist

32

Why are there so many side effects associated with cholinoceptor antagonists?

Control of CNS involves all muscarinic receptors, therefore use of antagonists associated with many side effects

33

How can cholinoceptor antagonists be used as premedication for anasthesia?

Atropine
- Reduces respiratory secretion, therefore minimies risk of aspiration

34

What effects does the parasympathetic nervous system have on the eye?

Causes
- Constriction of pupil
- Contraction of cillary muscle to the lens, allowing for closer vision

35

What effects does the sympathetic nervous system have on the eye?

- Dilates pupil
- Relaxes ciliary muscle, allowing more light to enter the eye and far vision

36

What is glaucoma?

Increase in intraocular pressure due to accumulation of fluid

37

What effect does pupil dilation have on glaucoma formation?

Impedes drainage of fluid (humour) by blocking the canal of Schlemm

38

What is the most likely cause of glaucoma?

Diabetes
Raised glucose levels = raised osmosis = increase in intraoccular fluid = compression of optic nerve

39

What are the consequences of increase parasympathetic tone in the eye?

Beneficial to glaucoma
- Increases constriction of pupil
- Causes canal of schlemm to be unblocked
- Allows the drainage of extra fluid

40

Which receptor ligands are used to clinically treat glaucoma?

- The sphincter muscle in the eye has M3 muscarinic receptors
- Muscarinic agonists will activate contriction of spincter muscles, unblocking drainage path.

41

Givethree non-receptor treatments are used for glaucoma?

Protaglandin analogue - increases uveoscleral outflow
Carbonic anhydrase inhibitor - decrease aqueous formation by the cillary body
Topical symathomimetics - reduce intraocular pressure by decreasing aqueous production and increasing aqueous drainage

42

What would be the effects of increasing sympathetic tone of the eye?

Dilate the pupil
Causing raised intraocular pressure

43

What agents, active at adrenoceptos, are used clinically in the treatment of glaucoma

Beta blockers - slow down production of aqueous humour
Clonidine - alpha 2- adrenergic agonist - increases uveoscleral outflow