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Signaling Diversity Mediated by Muscarinic Acetylcholine Receptor Subtypes and Evidence for Functional Selectivity

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Functional Selectivity of G Protein-Coupled Receptor Ligands

Part of the book series: The Receptors ((REC))

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Abstract

Muscarinic acetylcholine (mACh) receptor subtypes (M1–M5) mediate many of the central and peripheral actions of acetylcholine. Although two mACh receptor subgroups (M1/M3/M5 and M2/M4) have been defined based on primary sequence similarities and G protein/effector coupling preferences, considerable overlap in the coupling of subtypes to different signaling pathways is evident from the literature. Here we summarize the available experimental evidence for single mACh receptor subtypes coupling via more than one G protein subtype, or independently of G proteins, to exert their cellular effects. We also critically analyze the current evidence for different ligands being able to activate selectively subsets of these downstream signaling readouts. We discuss why there is currently little available evidence for functional selectivity at mACh receptors and speculate whether this situation will change as more subtype-selective ligands, and ligands that act on mACh receptors at sites other than the acetylcholine binding site are developed and explored.

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    R.A. John Challiss

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    Kim A. Neve

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Challiss, R.J., Thomas, R.L. (2009). Signaling Diversity Mediated by Muscarinic Acetylcholine Receptor Subtypes and Evidence for Functional Selectivity. In: Neve, K.A. (eds) Functional Selectivity of G Protein-Coupled Receptor Ligands. The Receptors. Humana Press. https://doi.org/10.1007/978-1-60327-335-0_8

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