3.0 Peripheral Nervous System Flashcards Preview

MedST IB: Mechanisms of Drug Action (MoDA) > 3.0 Peripheral Nervous System > Flashcards

Flashcards in 3.0 Peripheral Nervous System Deck (93)
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1

Where does PSNS originate from?

Craniosacral
(CNs III, VII, IX and X + pelvic splanchnics)

2

Where does the SNS originate from?

Thoracolumbar

(T1 → L2/3)

3

What neurotransmitter is the exception by not being stored in vesicles?

NO

4

What is the releasable pool?

Vesicles that are already docked to the release sites. Able to release contents very quickly (200μs)

5

What is the reserve pool?

Vesicles that are associated with the cytoskeleton. Can augment vesicle population if more than releasable pool is needed

6

What are the different SNAREs?

v-SNARE
Synaptobrevin

t-SNARE
SNAP-25
Syntaxin

7

How many α helices do the following SNAREs have?
1) Synaptobrevin
2) SNAP-25
3) Syntaxin

1) Synaptobrevin - 1
2) SNAP-25 - 2
3) Syntaxin - 1

8

What is the core complex?

Complex of:
1) Synaptobrevin
2) SNAP-25
3) Syntaxin

The four α helices come together and form a leucine zipper to bring plasma membranes together

9

What is synaptotagmin?

Ca²⁺ sensor on vesicle

Transmembrane region (N terminus)
Sequence homology with PKC

Binds several Ca²⁺ with low affinity

10

What are synapsins?

Found on surface of vesicles
Link vesicle to cytoskeleton
Non-phosphorylated → vesicles are immobile
Phosphorylated (by PKA + CaM kinase II) → dissociation → vesicles are free to move

11

What are the symptoms of botulinum poisoning?

1. Somatic muscle weakness (can lead to need for respiratory support)
2. Loss of cholinergic activity (consitipation, blurred vision, dry skin, urine retention)
3. Noradrenergic nerve actions (heart rate slowed)

12

What is the mechanism of Botulinum toxin?

- Preferentially effects cholinergic neurons
- Has a light chain and heavy chain
- C-terminus (heavy chain) binds ganglioside receptor (GT1b) ⟶ endocytosis of complex
- N-terminus translocates light chain from the endosomal lumen ⟶ cell cytoplasm (Does so by making a channel in endosomal membrane)
- Light chain has peptidase activity ⟶ cleaves target SNARE

13

What is the mechanism of tetanus toxin?

- Does not act directly on motor neuron
- Retrogradely transported to the cell body ⟶ transfers to inhibitory interneuron ⟶ disables interneuron from releasing its transmitter ⟶ motor neuron becomes more excitable

14

What are the SNARE targets for botulinum and tetanus toxin?

"
"

15

What is the rate limiting step in ACh production?

Supply of choline

16

What protein transports ACh into vesicles?

VAChT (vesicular ACh transporter)

17

What other neurotransmitters are found in ACh vesicles?

ACh + ATP (10:1)

Also some VIP sometimes

18

Whats the structure of AChE?

3 x tetramer of AChE bind to a tail via disulphide bonds
Tail binds to basement membrane via heparin sulphate proteoglycan

19

What is the mechanism of action of cholinesterases?

AChE + BuChE = Serine hydrolases

AChE
2 binding sites:
1) Anionic site (contains glutamate. Binds choline)
2) Esteratic site (Contains Serine + histidine)

BuChE
Lacks anionic site therefore ↓ affinity for ACh

20

What is the structure of nAChR?

Pentamer
2 x α + combination of 3 other subunits (e.g. βγδ)

21

What are the different muscarinic receptors?

Several different types. Important ones:

M1
- Location = Peripheral and central neurons
- G-protein = G₁₁/q

M2
- Location = Heart + pre-synaptic terminals
- G-protein = Gi

M3
- Location = Secretory glands + smooth muscle
- G-protein = G₁₁/q

22

What is the synthesis pathway for catecholamines?

Tyrosine → DOPA → Dopamine → NA → A

1) Tyrosine hyroxylase
2) Dopa decarboxylase
3) Dopamine beta-hydroxylase
4) PNMT

23

What is the rate limiting step in catecholamine synthesis?

Tyrosine hydroxylase

24

What is the ratio of NA:ATP in noradrenaline vesicles?

4:1
NA:ATP

25

What transporter transports DA and NA into vesicles?

Vesicular monoamine transporter (VMAT2)

H⁺ = energy source (2H⁺ extruded for every amine taken into vesicle) ← ATP dependent

26

Which two adrenoreceptors act as auto receptors?

α2
- Main one
- Activation → ↓ NA release (main effect is via G protein gated K⁺ channel

β2
- Activation → ↑ NA synthesis

27

What are the different types of uptake for inactivation of catecholamines?

Uptake 1
- Uptake into presynaptic neuron
- Affects response
- High affinity/low capacity
- Transporter = NET
-Na+ dependent
- NA > Adr

Uptake 2
- Uptake into postsynaptic neuron
- No effect on response
- Low affinity/High capacity
- Transporter = ENT (OCT3)
- Not Na+ dependent
- Adr > NA

28

What enzymes are involved in metabolism of catecholamines?

1) MAO
- On outer mitochondrial membrane
- MAO-A → NA, Adr, DA + 5-HT
- MAO-B → DA

2) COMT
- In liver and neuronal tissues
- Associated with uptake 2

29

What are the G-proteins coupled to the different adrenoreceptors? What are their effects?

"
"

30

What are the affinities for Adr and NA at the different adrenoreceptors?

α1 - NA > Adr
α2 - Adr > NA
β1 - Same
β2 - Adr > NA
β3 - Same