Cholinergic Signalling Flashcards
Acetylcholine
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)
AChase
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)
ANS
2 synapses + varicosities
- more widespread effect
- pockets with NT, string of vesicles (can effect LG number of target cells, high diffusion)
Paravertebral Chain Ganglion
Bulk of SNS pre-ganglionic neurons synapse here
Actions of the ANS
Glands
Cardiac Muscle
Smooth Muscle (blood vessels, digestive tract)
Presynaptic Axon Terminals (auto-receptors)
Muscarinic Receptor
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
M1/3/5 (Odd)
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
M2/4 (Even)
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
Nicotinic Receptor
Ligand-gated ion channels -2 types: Nm/1 Nn/2 5 total subunits Open = Na+ in, K+out Primary get depol.
Nm/1
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
Nn/2
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
AChase Substrate
Ach (N + M)
Methacholine (M)
AChase Resistant
Carbachol (N+M)
Bethanechol (M)
Anti-AChase
- Reversible
- Irreversible
Prevents ACh breakdown, inc ACh activity on receptors
- Donezepil
- Neostigme
- Physostigmine
- Organopesticides
- Nerve gas (chem warfare)
Pilocarpine
Glaucoma - topical
Xerostomia/dry mouth - oral
Carbachol
Topical treatment for glaucoma
Physostigmine
Treatment for glaucoma
Glaucoma
- 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
Xerostomia/Dry Mouth
not normal dry mouth - d/t complication of radiation therapy of head/neck damage to salivary gland
Agonist = Pilocarpine (oral)
Side effects = dec HR
Diagnosing Lung Conditions
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
Megacolon
Dilated bowel
- poor contraction
- major constipation
- lazy bowel
Damage from Crohn’s colitis, surgery
Agonist = Bethanechol (oral)
Anti-AChase = Neostigmine
Urine Retention
Stimulates bladder contraction
Agonist = Bethanechol (oral)
Anti-AChase = Neostigmine
