Cholinergic Signalling

Question 1

Acetylcholine

Answer 1

Made of acetyl-CoA + choline
Catalyzed by ChAT
Lives in vesicles (placed in their by VAChT)
Only NT that is metabolized in the cleft by AChase
Binds nAChR (ion channels) or muscarinic (GPCR)

Question 2

AChase

Answer 2

Metabolizes ACh into acetate & choline
Bound to EC protein (in network) on post-synaptic neuron
PseudoAChase = found in blood + liver (impacts PK & PD of diff drugs + doses)

Question 3

ANS

Answer 3

2 synapses + varicosities

• more widespread effect
• pockets with NT, string of vesicles (can effect LG number of target cells, high diffusion)

Question 4

Paravertebral Chain Ganglion

Answer 4

Bulk of SNS pre-ganglionic neurons synapse here

Question 5

Actions of the ANS

Answer 5

Glands
Cardiac Muscle
Smooth Muscle (blood vessels, digestive tract)
Presynaptic Axon Terminals (auto-receptors)

Question 6

Muscarinic Receptor

Answer 6

All GPCR
5 Subtypes - diff pathways depending on which protein it’s coupled to
Many M receptors = M3
M1/4/5 = CNS (lots)
M2/3 = Inc in CNS
Still need to 2 Ach binding to alpha subunits

Question 7

M1/3/5 (Odd)

Answer 7

Couple to Gq/11
Cause activation (secrete or contraction)
Use PKC or IP3 method of signalling

Ex. M3 = inc intestine movement, inc activation/activity of PSNS

Question 8

M2/4 (Even)

Answer 8

Couple to Gi/o
Cause inhibition
Dec cAMP b/c dec AC

Ex. M2 = K+ leaks out, PSNS - SA node potential
-Inhibitory b/c get more hyperpolarization

Question 9

Nicotinic Receptor

Answer 9

Ligand-gated ion channels
-2 types:
Nm/1
Nn/2
5 total subunits
Open = Na+ in, K+out
Primary get depol.

Question 10

Nm/1

Answer 10

2 a, b, sigma, delta
4 diff subunits
Many diff subtypes of each subunit, bind drugs that are more/less selective for 1 over the other

Question 11

Nn/2

Answer 11

mix of a & b, or all a
2 diff subtypes
Many diff subtypes of each subunit, bind drugs that are more/less selective for 1 over the other

Question 12

AChase Substrate

Answer 12

Ach (N + M)

Methacholine (M)

Question 13

AChase Resistant

Answer 13

Carbachol (N+M)

Bethanechol (M)

Question 14

Anti-AChase

• Reversible
• Irreversible

Answer 14

Prevents ACh breakdown, inc ACh activity on receptors

• Donezepil
• Neostigme
• Physostigmine
• Organopesticides
• Nerve gas (chem warfare)

Question 15

Pilocarpine

Answer 15

Glaucoma - topical

Xerostomia/dry mouth - oral

Question 16

Carbachol

Answer 16

Topical treatment for glaucoma

Question 17

Physostigmine

Answer 17

Treatment for glaucoma

Question 18

Glaucoma

Answer 18

• Build up of fluid/P in the retina
• Pushes on optic nerve + can’t exit the Canal Schiemm

Tx

• Activate M receptors
• Contract pupil + ciliary muscles
• Pulls on trabecular meshwork (inc. space)
• Opens pores (better flow out, dec P)

Agonists: topical, Carbachol, pilocarpine

Anti-AChase: physostigmine

Question 19

Xerostomia/Dry Mouth

Answer 19

not normal dry mouth - d/t complication of radiation therapy of head/neck damage to salivary gland

Agonist = Pilocarpine (oral)

Side effects = dec HR

Question 20

Diagnosing Lung Conditions

Answer 20

Diagnostic for Asthma

Agonist: Methacholine (only binds M)
-Constricts bronchii

Connect to spirometer, measures air flow into lungs

• Asthmatics = narrows much more (@ lower dose)
• lower dose = LG’er drop in air flow

Question 21

Megacolon

Answer 21

Dilated bowel

• poor contraction
• major constipation
• lazy bowel

Damage from Crohn’s colitis, surgery

Agonist = Bethanechol (oral)

Anti-AChase = Neostigmine

Question 22

Urine Retention

Answer 22

Stimulates bladder contraction

Agonist = Bethanechol (oral)

Anti-AChase = Neostigmine