Peripheral neural transmission: Cholinergic (nicotinic) transmission Flashcards Preview

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Flashcards in Peripheral neural transmission: Cholinergic (nicotinic) transmission Deck (25):
1

Hemicholium

Blocks transporter that transports choline into nerve cell

2

Vesamicol

Non-competitive, reversible blocker of VAChT (SLC18A3)

3

ACh storage vesicles

Appear electron-lucent in electron micrographs.
Contain ACh:ATP in ration 10:1
Estimates of ACh content of vesicles range 1,000 to >50,000 molecules

4

VIP storage vesicles

Dense-cored
Found in some cholinergic nerves

5

Botulinum toxin

Blocks ACh release by cleaving target SNARE
May lead to respiratory failure

6

beta-bungaratoxin

Blocks ACh release
Acts through a phospholipase A2 rather than peptidase activity
Localises to the membrane by a K+ channel binding moiety

7

alpha-latrotoxin

Venom of black widow spider
Binds to neurexins (TM proteins on nerve PM)
Causes massive release of ACh

8

BuChE (butyrylcholinesterase)

Much broader substrate specificity than AChE
Also breaks down LA procaine
Made in the liver, found mainly in plasma

9

AChE

Relatively specific for ACh
Found in :
synaptic cleft (3 tetramers of AChE attached by disulphide bonds to collagenous tail. Tail localises the enzyme by binding to a heparan sulphate proteoglycan in the basement membrane. Each tetramer cluster contains 12 sites for ACh hydrolysis- can breakdown ACh within c.1ms)
presynaptic nerve terminal (soluble)

10

alpha-bungarotoxin

Irreversible antagonist of nicotinic ACh R at n.m.j. Also affects brain (a7)5 isoform

11

Hexamethonium

Channel pore blocker of nicotinic ACh R.
Use-dependent blockage of ganglionic transmission.

12

d-tubocurarine

Purified product of curare
Agonist at nicotinic ACh R -> depolarizing block
Relatively non-selective between ganglion & n.m.j at clinical doses
Quaternary ammonium compound- not orally active

13

Atracurium

Competitive antagonist at n.m.j nicotinic ACh R.
(non-depolarizing blocker)
Quaternary ammonium compound- not orally active
Ester- broken down by spontaneous hydrolysis and plasma esterases

14

Pancuronium

Competitive antagonist at n.m.j nicotinic ACh R.
(non-depolarizing blocker)
Quaternary ammonium compound- not orally active
Longer action than atracurium, not hydrolyses

15

Selective non-depolarising neuromuscular blocking agents

Atracurium and pancuronium
Competitive antagonists of nicotinic R
Cause 'tetanic fade'-thought to be due to block of nicotinic 'autoreceptors' which give positive feedback to maintain transmitter release.
Used in anaesthesia to produce muscle relaxation (affect fast 'white' > slow 'red')
Reversed by anticholinesterases

16

Nicotine

Depolarising blocker (long acting agonist) at ganglionic nicotinic ACh receptors

17

Decamethonium

Depolarising blocker (long acting agonist) of nicotinic ACh R
Selective for n.m.j form

18

Suxamethonium

Depolarising blocker (long acting agonist) of nicotinic ACh R. Selective for n.m.j form
Very short duration of action, used in intubation.
Ester, broken down by plasma BuChE

19

Depolarising block and AChEs

In phase I (inactivation of VGNaC): AChEs deepen blockade. Can be opposed by non-depolarising blockers
In phase II (desensitisation of nicotinic R): AChEs reverse blockade

20

Atropine

Muscarinic antagonist

21

Muscarine

Muscarinic agonist

22

Acetyl-β-methylcholine aka methacholine

Muscarinic agonist
2 isomers: neither is hydrolysed by BuChE
(+)methacholine is a substrate for AChE, and ~200x more potent than (-) isomer at muscarinic receptors. (-) isomer has no affinity

23

Isoprenaline (compare to Acetyl-β-methylcholine)

β-adrenoceptor agonist
Inactive isomer has affinity, but no efficacy.

24

Benzylcholine mustard

Irreversibly alkylates the muscarinic receptor
Introduces the concept of spare receptors or receptor reserve- as progressively reacts with receptors, at first a maximum response with ACh is still attainable. Parallel shift of log concentration/ response curve.

25

Trimetaphan

Competitive antagonist
Selective for ganglionic form of nicotinic receptor