PHA3011 Lecture Notes - Lecture 3: Muscarinic Agonist, Nicotinic Acetylcholine Receptor, Decamethonium
Lecture 3 Peripheral neurotransmission – nicotinic and
muscarinic receptors
ACh receptors
Muscarinic (mAChR) (5 subtypes)
• Parasympathetic neuroeffector junction
• Vasculature endothelial cells NO release
vasodilation (these are not innervated by the
PSN – need to consider when giving someone a
muscarinic agonist ect.)
• Sympathetic cholinergic neuroeffector
junctions (sweating response)
• Are GPCR can cause graded responses
Nicotinic (nAChR) (multiple subtypes)
• Skeletal muscle contraction
• Autonomic ganglia stimulate postganglionic
nerves
• Adrenal medulla adrenaline release
Nicotinic receptors have a pentameric structure. There
are multiple subtypes based on subunits that make up
this structure. They are ligand gated ion channels. Ach
binds to alpha subunits of the N receptor. Ion channel
opens; Na+ enters’ local depolarisation. Depolarisation
will spread; contraction (each individual muscle fibre is
an all or nothing response). The configuration of each
nicotinic receptor influencing selectivity for different
agonists and antagonists.
There are the nicotinic muscular type which are N2-
ligand gates ion channel located at the neuromuscular
junction. ACh open Na+ channel causing depolarisation
and subsequent action potential at NMJ. N2 nicotinic
NMJ binds to: decamethonium > hexamethonium.
The nicotinic neuronal type are N1-neuronal-nicotinic
ligand-gates ion channel at ganglia. ACh opens Na+
channel causing depolarisation and subsequent action
potential at all ganglia and the adrenal medulla. N1
nicotinic binds to: hexamethonium > decamethonium.
Skeletal muscle contraction
One motor nerve innervates many muscle fibres.
Skeletal muscle transmission occurs via:
1. Depolarisation of the motor end place in
response to the binding of ACh to nicotinicM
receptors.
2. Depolarisation of the end plate triggers a wave
of depolarisation (AP) to move down the entire
muscle membrane
3. Repolarisation follows unbinding of ACh from
the end plate nicotinicM receptors.
Ion channel stays open for as long as the agonist stays
in contact with the receptor. But for a muscle fibre to
continue to response to nerve stimulation the ion
channel must reset and muscle fibre must recover
(repolarise).
When the nerve is activated we see contraction of many
muscle fibres. The strength of contraction is dependent
on how many muscle fibres are recruited in this
contraction. The more fibres the stronger the response.
Agents affecting nicotinic receptors
Muscle type agonists
• ACh - cannot differentiate between muscarinic
and nicotinic
• CCh (carbachol) – cannot differentiate between
muscarinic and nicotinic
• Suxamethonium
Muscle type antagonists
• Tubocurarine
Ganglion type agonists
• ACh
• CCh (carbachol)
• Epibatidine
• DMPP
Ganglion type antagonists
• Mecamylamine
• Trimetaphan
Nicotinic receptor antagonists = non-depolarising NM
blockers do not cause any affect (they block ACh from
binding)
• Tubcocurarine (long duration; 60-120 min)
quaternary compound, not absorbed orally
(used in hunting, kill prey, humans eating pray
will not be affected). Causes a ganglion
blockade – CNS effects and histamine release
from mast cells (a pseudo-allergic response)
• Gallamine
• Vecuronium (30-40min)
Document Summary
Lecture 3 peripheral neurotransmission nicotinic and muscarinic receptors. Muscarinic (machr) (5 subtypes: parasympathetic neuroeffector junction, vasculature endothelial cells no release vasodilation (these are not innervated by the. Psn need to consider when giving someone a muscarinic agonist ect. : sympathetic cholinergic neuroeffector junctions (sweating response, are gpcr can cause graded responses. Nicotinic (nachr) (multiple subtypes: skeletal muscle contraction, autonomic ganglia stimulate postganglionic nerves, adrenal medulla adrenaline release. There are multiple subtypes based on subunits that make up this structure. Ach binds to alpha subunits of the n receptor. Depolarisatio(cid:374) will spread; contraction (each individual muscle fibre is an all or nothing response). The configuration of each nicotinic receptor influencing selectivity for different agonists and antagonists. There are the nicotinic muscular type which are n2- ligand gates ion channel located at the neuromuscular junction. Ach open na+ channel causing depolarisation and subsequent action potential at nmj. Ion channel stays open for as long as the agonist stays in contact with the receptor.
