CHOLINORECEPTORS Flashcards
Acetylcholine has a permanent positive charge. True or false?
True
What is acetylcholine broken down into and what facilitates this?
Acetate and choline
Acetylcholinesterase
What happens to choline when ACh is broken down?
Gets recycled - taken back to presynaptic nerve terminal
Describe the series of events in cholinergic transmission
AP comes down neuron and depolarises the nerve terminal
depolarisation activates voltage sensitive calcium channels
Ca2+ enter the presynaptic nerve terminal and cause vesicles that contain ACh to fuse with the membrane, releasing contents into synapse
ACh interacts with the receptor and has an effect on target organ
ACh broken down by AChE into acetate and choline
Where does synthesis of ACh take place?
presynaptic nerve terminal
Muscarinic receptors are GPCRs and are slower than nicotinic receptors. True or false?
True
Nicotinic receptors are ligand-gated ion channels. True or false?
True
Only muscarinic receptors are found in the CNS. True or false?
False - muscarinic and nicotinic are found in CNS
Where are muscarinic receptors found?
CNS
Parasympathetic
Sympathetic (less)
Where are nicotinic receptors found?
CNS
NMJ
Autonomic ganglia
Describe the structure of nicotinic receptors
Have a pentameric structure - 2 a, B, delta and epsilon
18 subunits
at least 2 ACh binding sites (on a)
quick response
Name two nicotinic receptor agonists.
Nicotine
Suxamethonium
Name three nicotinic receptor antagonists
Atracurium
Tubocurarine
alpha bungarotoxin
What is the structural difference of a foetal nicotinic receptor?
Instead of epsilon, gamma
Describe the structure of a muscarinic receptor.
Monomeric M1-5 subtypes 5 receptor types Binding site for G protein 1 ACh binding site per subunit Response is slower than nicotinic
Name two muscarinic receptor agonists
Muscarine
Pilocarpine
Name two muscarinic receptor antagonists
Atropine
Hyoscine
Which receptors do anti-emetic and anti-asthma drugs work on?
Muscarinic
Paralysing agents in surgery work on nicotinic receptors. True or false?
True
Drugs used in eye exams and to treat glaucoma work on which receptors?
Muscarinic
ACh receptors are divided into two types. What are they?
Nicotinic receptors
Muscarinic receptors
Botox works on release of acetylcholine. True or false?
True
Drugs that treat myasthenia gravis act on AChE. True or false?
True
Drugs that treat Alzheimer’s disease act on ACh release. True or false?
False - act on AChE (ACh metabolism)
How do non-depolarising blockers at nAChRs block neuromuscular transmission?
Competitive antagonists - produce flaccid paralysis in patients
How can effects of non-depolarising blockers at nAChR be reversed?
Give drug that increases conc of ACh (i.e. inhibitor of AChE)
How do polarising blockers work at nAChRs?
They are agonists, not broken down by AChE. Patients experience a muscle twitch before flaccid paralysis
Why doesn’t a patient that’s taking a depolarising blocker experience tetany?
Because depolarisation is sustained as a result of activation of the receptor and this leads to desensitisation to electrical activity.
The effects of depolarising blockers can be reversed by AChE inhibitors. True or false?
False - makes situation worse as they add agonist
Which is the only depolarising blocker that is currently clinically used?
Suxamethonium
What are examples of non-depolarising blockers used in surgery?
Atracurium
Rocuronium
Pancuronium
Atracurium breaks down spontaneously. True or false?
True
Pancuronium has a long duration of action and is used in euthanasia. True or false?
True
Muscarinic agonists are not widely used. What are the two examples in which they are used?
pilocarpine in glaucoma
bethanechol in bladder disorders
Muscarinic antagonists are widely used because muscarinic receptors are widespread throughout parasympathetic and CNS. True or false?
True
Muscarinic antagonists block parasympathetic nervous system, leading to bradycardia. True or false?
False - tachycardia
Atropine is a muscarinic antagonist. What is its use in surgery?
Prevent bronchial secretions during surgery
Tiotropium and ipratropium are muscarinic agonists used as second line bronchodilators in asthma. True or false?
False - muscarinic antagonists
Systemic effects of botulinum toxin can lead to death. True or false?
True
How does the botulinum toxin block the release of ACh?
Breaking down snare proteins
Irreversible AChE jnhibitors are used therapeutically. True or false?
False
Sarin is a reversible AChE inhibitor. True or false?
False - irreversible
Irreversible AChE inhibitors cause muscle paralysis, although they result in uncontrollable amount of ACh in synapse which should lead to contraction. Why?
Because nAChR can exist in an open state, closed state and a desensitised state.
After a few contractions, due to ACh being present, the muscle becomes flaccid.
This is because the desensitised state is switched on when the receptor is exposed to ACh for a prolonged period of time - ACh still binds but the channel closes
Also, if nAChRs are open continuously, they will be continuously depolarised and so no further APs take place
Net effect of these factors result in no muscle contraction
Describe the molecular mechanism of sarin
Serine is important in the function of AChE as it accepts the acetate group that is released from Ach breakdown
Acetyl-serine residue is broken down to recycle the active site back it its starting form
Sarin attaches to serine
Sarin-serine bond too strong to be broken down and the enzyme is not recycled = dead
Which drug is injected I.M to save the life of someone that has been exposed to sarin?
Atropine (muscarinic antagonist)
