BIOL 2P94 Lecture Notes - Sympathetic Nervous System, Bradycardia, Choline Acetyltransferase
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Published on 4 Feb 2013
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Outline of Lecture 08 (02-20 A; Baraban)
Monoamines I
I. There are three basic criteria for proving a substance is a nxt
1) Sufficient: substance mimics endogenous response
2) Necessary: receptor antagonist block response due to substance
3) Presence: substance is the endogenous agent (e.g. can be isolated/purified)
Acetylcholine Norepinephrine
Autonomic
nervous system
Parasympathetic Sympathetic
Biochemical
synthesis
Acetyl CoA + Choline ACh
Catalyzed by choline acetyltransferase
Multistep:
Tyr DOPA Dopamine NE
(NE Epi, in adrenal medulla)
Vesicular
entrapment
• High affinity choline uptake into presyn.
• ACh synthesis in cytoplasm
• Vesicular ACh transporter
Vesicular dopamine transporter (therefore
NE synthesis occurs within vesicle)
Inactivation ACh Acetic acid + choline
Catalyzed by ACh-esterase (AChE)
High affinity NE uptake
Pharmacology • Muscarine: muscarinic receptor agonist
• Atropine: muscarinic receptor
antagonist, reverses bradycardia
• Nerve gas: irreversible inhibitor of
AChE
• Curare: nicotinic receptor antagonist,
paralyzes diaphragm and skeletal muscles
• Cocaine: blocks NE uptake, tachycardia
Receptors • Muscarinic: parasympathetic, 5
subtypes, (e.g. M2 expr by heart), all
GPCR’s
• Nicotinic: neuromuscular junctions,
ionotropic
All GPCR!
•
α
: smooth muscles (e.g. vascular BP
effects)
•
β
: sympathetic to heart
Subtypes not listed here
(From this, be able to predict
agonist/antagonist effects)
II. Some general principles regarding nxt’s
- The 2 major nxt of the autonomic system are ACh and NE
- There is often many different receptors for the same nxt, and further, subtypes of those receptors
∴ the subtypes are coupled to distinct signaling pathways
∴ can create selective inhibitors to create a specific, desired effect
- Ionotropic receptors have fast on and off responses, where as GPCR have slow on and off
responses (think what molecular events occur to figure out why)
- Many GPCR’s are in close proximity to the ion channel they modulate, thereby mimicking a
ionotropic receptor and ensuring a specific effect
Summary of major points
- See objectives at beginning of lecture notes