Acetylcholine Flashcards
What are the 6 criteria for NT
- Presynaptic cell should contain the substance as well as a mechanism to synthesise it
- Substance should be released when depolarizing stimulus is applied to the neuron
- Receptors should be present on the postsynaptic cell
- Known antagonists should block the effects
- A system to inactivate the substance must exist
- Exogenous application of the substance to the postsynaptic cell should produce the same response
what are neuromodulators?
they are hormone-like in which they act at a distance, and they do not elicit a direct effect on the postsynaptic cell but instead alters the action potential of a NT whether it enhances, reduces or prolongs it.
what are the 5 neuromodulators?
- autocrine (self acting)
- juxtacrine (adjacent)
- paracrine (near)
- endocrine (far)
- exocrince (outside)
True or false: neuromodulators function in anterograde or in a retrograde manner, where the pre-synaptic can have an effect on the postsynaptic and vise versa.
true
which cells are neuromodulators released from?
glial cells
True or false: acetylcholine was the first NT to be identified, which is a common NT at the neuromuscular junction in the periphery (motor neurons releasing it on to the muscles).
true
what are the neurons that use acetylcholine termed?
cholinergic, as they are cells that release acetylcholine
what is the synthesis of acetylcholine?
acetyl-coenzyme A + choline —> acetylcholine
ChAT
ChAT-> acetyltransferase
where is ChAT only expressed in?
in the cytoplasm of neurons that use acetylcholine as a NT
where is choline primarily derived from?
from hydrolysis of dietary lipids (e.g., legumes, red meat and it is highest in livers) by phospholipase D
what happens if an athlete is low in choline?
gets tired easily
True or false: choline is water soluble and can cross the BBB anytime
False, although it is water soluble it is only capable of crossing the BBB due to the presence of specific choline receptors
how is acetylcholine metabolized?
it is metabolized by the enzyme acetylcholinesterase (AChE) to choline and acetic acid/ acetate
where does choline synthesis occur?
in the axon itself
where does ACh get broken down?
it gets broken down in the synapse itself
what does VAChT do?
it transfers ACh into its vesicles to be transported
True or false: ACh synthesis is tightly regulated
true
what are the three ways in which ACh synthesis is regulated?
- Product inhibition-> high levels in the cell inhibit the synthesis of further ACh by ChAT
- Precursor availability-> increasing dietary choline has been used to treat conditioner where the cholinergic system has been damaged (Alzheimer) but no success
- Neuron activity (increased during high activity)-> activity dependent synthesis ensures sufficient ACh is available during period of high activity
True or false: there is a limiting amount that you body uses, no matter how much you consume.
true
True or false: more active means more synthesis
true
Where is ACh stored?
ACh is stored in vesicles at the nerve terminal by vesicular ACh transporter
What drug inhibits the transportation of ACh?
Vesamicol, leads to cystolic accumulation of ACh and blocking vesicle transport depletes the pool of release-ready vesicles
True or false: you can only release VAChT with an action potential.
False, it can be done without an action potential
How is ACh released?
It is released by classical vesicular exoctyosis (voltage dependent Ca2+-influx)
What is the release of ACh triggered by?
Triggered by latrotoxin in periphery, if bitten by a black widow it would cause muscle pain, tremors, nausea, excessive sweating
True or false: latrotoxin can cross the BBB
false, it cannot
Where is AChE primarily present in and what does it do?
It is in the synaptic cleft and breaks ACh down to choline
What transporter is choline transported by?
choline receptor
True or false: only a small amount of choline is recycled to ACh.
False, majority of it is recycled
What drug is re-uptake inhibited by and what happens?
Hemicholinium, leads to synaptic accumulation of choline and result in run-down activity
What is another name for botox?
Clostridial neurotoxins
What does botox do?
causes paralytic effects of botulism poisoning, injections causes muscle paralysis by inhibiting ACh release
Fill in the blank: may drugs affecting cholinergic systems are________
Insecticidal
True or false: ACh is a primary neurotransmitter of the insect CNS
true
What are plant alkyloids?
They are secondary metabolites commonly synthesized for defense against insect or animal predation
True or false: insecticides can cross the BBB, and can affect humans.
False, they cannot cross the BBB
True or false: when there is an AChE inhibition,it decreases the rate of ACh breakdown leaving more ACh to act at postsynaptic receptors
true
What is the plant-derived toxin that is BBB permeable inhibitor of AChE?
a. Physostigmine
b. Pyridostigmine
c. Neostigmine
a
What are symptoms of accidental poisoning of physostigmine?
Slurred speech, confusion, hallucination, loss of reflex, coma, death
What drugs are used to treat myasthenia gravis
Synthetic BBB-impermeable analogues neostigmine (prostigmin) and pyridostigmine (mestionon)
True or false: physostigmine, neostigmine and pyridostigmine are irreversible inhibitors of AChE
False, are reversible inhibitors of AChE
True or false: neostigmine increases in ACh in the periphery system
true
What does myasthenia gravis (MG) result from?
Immune response to ACh receptors at neuromuscular junction– attenuating response to ACH signals
What occurs from treatment with AChE inhibitiors for MG?
It prolongs the ACh signals and compensates for the lost functions
True or false: organophosphate pesticides (malathion) inhibits AChE irreversibly.
true
True or false: Organophosphate are more sensitive to humans than insects
false, insects are more sensitive but human toxicity is possible
What is sarin and VX?
They are nerve gas and are irreversible AChE inhibitors
What is prescribed as a preventive agent to nerve gas poisoning?
Pyridostigmine
True or false: things that are irreversible are terminal and results in death
true
What was pyridostigmine later found to increase?
It was found to increase BBB permeability under stress conditions
