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Cholinergic receptors

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An acetylcholine receptor (abbreviated AChR) is an integral membrane protein that responds to the binding of the neurotransmitter acetylcholine.

Classification

Like other transmembrane receptors, acetylcholine receptors are classified according to their "pharmacology", or according to their relative affinities and sensitivities to different molecules. Although all acetylcholine receptors, by definition, respond to acetylcholine, they respond to other molecules as well.

Receptor types

Molecular biology has shown that the nicotinic and muscarinic receptors belong to distinct protein superfamilies.

The nAChRs are ion channels, and, like other members of the "cys-loop" ligand-gated ion channel superfamily, are composed of five protein subunits arranged like staves around a barrel. The subunit composition is highly variable across different tissues. Each channel contains two alpha subunits, a beta, a gamma, and a delta. Binding of acetylcholine to the N termini of each of the alpha subunits results in activation of the channel. Each subunit contains four regions named M1, M2, M3, and M4, which probably span the membrane. The M2 region, which sits closest to the pore lumen, forms the pore lining. The pore formed when the nAChR channel is open is permeable to both Na+ and K+ ions.

In contrast, the mAChRs are not ion channels, but belong instead to the superfamily of G-protein-coupled receptors that activate other ionic channels via a second messenger cascade.

Role in health and disease

Nicotinic acetylcholine receptors can be blocked by curare and toxins present in the venoms of snakes and shellfishes. Drugs such as the neuromuscular blocking agents bind reversibly to the nicotinic receptors in the neuromuscular junction and are used routinely in anaesthesia.

Nicotinic receptors are the main mediator of nicotine from tobacco addiction. In myasthenia gravis, the receptor is targeted by antibodies, leading to muscle weakness. Muscarinic acetylcholine receptors can be blocked by the drugs atropine and scopolamine.

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