Muscarinic receptor subtypes and their principal functions
THE CONTEXT
Muscarinic receptors mediate neuronal, cardiac, smooth muscle, glandular and endothelial responses. A tissue may express several subtypes while one predominates.
M1 receptors
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M1 is primarily neuronal, occurring on ganglion cells and enteric and central neurons, especially in the cortex, hippocampus and corpus striatum.
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M1 participates in gastric and intestinal secretion, vagally induced relaxation of the lower esophageal sphincter, and learning, memory and motor functions.
M2 receptors
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Cardiac muscarinic receptors are predominantly M2 and mediate vagal bradycardia.
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Autoreceptors on cholinergic nerve endings are also M2 receptors.
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Smooth muscle expresses some M2 receptors that mediate contraction, as do M3 receptors.
M3 receptors and overlapping actions
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M3 receptors mediate visceral smooth muscle contraction and glandular secretion.
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M3 receptors also mediate vasodilatation through release of endothelium-dependent relaxing factor.
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Most smooth muscles and glands contain both M2 and M3 receptors, with M3 predominating.
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M2 and M3 together mediate most recognized muscarinic actions, including contraction of the lower esophageal sphincter.
Receptor organization
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Muscarinic receptors are G-protein-coupled receptors with seven membrane-traversing amino acid sequences.
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Acetylcholine activates, and atropine blocks, all three major muscarinic receptor subtypes described here.