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Drugs: From Molecules to Man - Lecture 8 (23/02/2018)
Cholinergic and Adrenergic Transmission
As its name suggests, cholinergic transmission involves acetylcholine as the neurotransmitter.
There are two features of Acetylcholine (ACh) that should be highlighted:
1) It has a permanent positive charge, so it will not dissolve in membranes. The positive charge is also one of the structural features that is necessary for it to bind to its receptors.
2) The second feature is the Ester linkage, which is important in the breakdown of ACh. It is at this point where the molecule is cleaved to terminate its synaptic action.
The mechanisms here show Ca2+ stimulating vesicle fusion with the presynaptic membrane, and thus the exocytosis of ACh have been fully covered in Excitable Cells.
The enzyme Acetylcholinesterase (AChE) breaks down Ach into Acetate and Choline through the cleavage of the Ester bond.
The Choline is taken back up into the nerve terminal d via a carrier and is then made recycled back into ACh by the enzyme Choline acetyl transferase. ACh is then transported into vesicles and then stored ready for release.
Acetylcholine Receptors: Nicotinic vs Muscarinic
Dale discovered in 1914 that:
Muscarinic Receptors have G-protein coupled channels, (Slow transmission).
Nicotinic Receptors have Ligand-gated ion channels, (Fast transmission).
ACh Receptors are divided into Muscarinic and Nicotinic types.
The Muscarinic type are GPCRs and are slower than the Nicotinic receptors, which are ligand-gated ion channels. These receptors are often abbreviated to mAChR and nAChR
Both types of receptor are found in the CNS and in the Periphery.
The Nicotinic receptors (nAChR) are particularly important at the skeletal muscle,
neuromuscular junctions and in Autonomic Ganglia.
The Muscarinic receptors (mAChR) are the main mediators of transmission to effector organs in the parasympathetic branch of the autonomic nervous system but they also play a role in a small number of sympathetic synapses too.
Drugs Acting at AChR include:
Paralyzing agents used in surgery.
Drugs used in eye exams.
Drugs used to treat glaucoma.
Drugs to treat nicotine addiction.
Alzheimer's disease drugs*.
Parkinson's disease drugs*.
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