Acetylcholine

Question 1

Criteria for Neurotransmitters (NT) 1

Answer 1

Presynaptic cell should contain the substance as well as a mechanism to synthesise it

Question 2

Criteria for Neurotransmitters (NT) 2

Answer 2

Substance should be released when depolarizing stimulus is applied to the neuron

Question 3

Criteria for Neurotransmitters (NT) 3

Answer 3

Receptors should be present on the postsynaptic cell

Question 4

Criteria for Neurotransmitters (NT) 4

Answer 4

Known antagonists should block the effects

Question 5

Criteria for Neurotransmitters (NT) 5

Answer 5

A system to inactivate the substance must exist

Question 6

Criteria for Neurotransmitters (NT) 6

Answer 6

Exogenous application of the substance to the postsynaptic cell should produce the same response

Question 7

Neuromodulators can be

Answer 7

hormone-like (acting at a distance)

Question 8

Autocrine

Answer 8

(self-acting)

Question 9

Juxtacrine

Answer 9

(adjacent)

Question 10

Paracrine

Answer 10

(near)

Question 11

Endocrine

Answer 11

(far)

Question 12

Exocrine

Answer 12

outside

Question 13

Neuromodulators May act at locations

Answer 13

other than the synapse

Question 14

Neuromodulators Does not

Answer 14

elicit a direct effect on the postsynaptic cell, but alters the action of a classical neurotransmitter

Question 15

Neuromodulators May function in

Answer 15

anterograde or retrograde manner

Question 16

Neuromodulators may be

Answer 16

released from glial cells

Question 17

Neurons that use acetylcholine are termed

Answer 17

cholinergic neurons

Question 18

acetylcholine is a

Answer 18

Common neurotransmitter at neuromuscular junctions in the periphery

Question 19

Synthesis of acetylcholine

Answer 19

Acetyl-coA + Choline – ChAT—> acetylcholine

Question 20

ChAT is only expressed in the

Answer 20

cytoplasm of neurons that use ACh as a neurotransmitter

Question 21

Choline is derived primarily from

Answer 21

from hydrolysis of dietary lipids (phosphatidylcholines) by phospholipase D.

Question 22

Choline is

Answer 22

is water soluble and is only capable of crossing the BBB due to the presence of specific choline transporters.

Question 23

metabolism of acetylcholine

Answer 23

acetylcholine —-AChE—> choline + acetate

Question 24

ACh synthesis is tightly regulated for three reasons

Answer 24

Product inhibition
Precursor availability (choline and acetyl-CoA)
Neuron activity (increased during high activity)

Question 25

product inhibition of acetylcholine

Answer 25

High levels of ACh in the cell inhibit the synthesis of further ACh by ChAT

Question 26

Precursor availability (choline and acetyl-CoA)

Answer 26

Increasing dietary choline has been explored as a treatment for conditions where the cholinergic system has been damaged (e.g. Alzheimer’s) – but not to any significant success

Question 27

Neuron activity (increased during high activity)

Answer 27

Activity-dependent synthesis ensures sufficient ACh is available during periods of high activity

Question 28

ACh Storage

Answer 28

Stored in vesicles at the nerve terminal by vesicular ACh transporter

Question 29

ACh transport

Answer 29

transported by vessicles

Question 30

Transport is inhibited by the drug

Answer 30

vesamicol Blocking vesicle transport depletes the pool of release-ready vesicles

Question 31

ACh Re-uptake

Answer 31

ACh is broken down in the synapse to attenuate signalling Breakdown product (choline) transported by choline transporter Majority of choline is recycled to ACh

Question 32

Re-uptake inhibited by the drug

Answer 32

hemicholinium-3

Question 33

Botox

Answer 33

Local injection causes muscle paralysis by inhibiting ACh release

Question 34

Insecticides and ACh

Answer 34

ACh is a primary neurotransmitter of the insect CNS

Question 35

Plant alkyloids

Answer 35

secondary metabolites commonly synthesized for defense against insect or animal predation

Question 36

AChE inhibition

Answer 36

prolongs ACh signalling

Question 37

AChE inhibition decreases the rate of

Answer 37

ACh breakdown in the synaptic cleft leaving more ACh to act at postsynaptic receptors

Question 38

Plant-derived toxin physostigmine is a

Answer 38

BBB permeable inhibitor of AChE (found in Calabar beans

Question 39

Synthetic BBB-impermeable analogues neostigmine (Prostigmin) and pyridostigmine (Mestionon) are used to treat the

Answer 39

autoimmune disease myasthenia gravis (MG)

Question 40

Physostigmine, pyridostigmine, and neostigmine are

Answer 40

reversible inhibitors of AChE

Question 41

Myasthenia gravis results from

Answer 41

immune response to ACh receptors at neuromuscular junctions – attenuating response to ACh signals. Treatment with AChE inhibitors prolongs the ACh signal and compensates for the lost function.

Question 42

malathion

Answer 42

inhibit AChE irreversibly

Question 43

Sarin and VX

Answer 43

nerve gas) are irreversible AChE inhibitors

Question 44

Pyridostigmine prescribed as

Answer 44

preventative agent to nerve gas poisoning

Question 45

Pyridostigmine later found to have increased BBB permeability under stress conditions

Answer 45

Use linked to one component of Gulf War Syndrome Confusion-ataxia syndrome Cognitive impairment, dizziness, balance and coordination problems