Commun Biol 2025 Dec 12;81:1764. doi: 10.1038/s42003-025-09143-z.

Characterisation of an unusual nicotinic acetylcholine receptor subtype preferentially sensitive to biogenic amines.

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Nicotinic acetylcholine receptors (nAChRs) are best known for mediating the fast actions of acetylcholine. However, the spectrum of other neurotransmitters possibly acting on these receptors is not well understood. Here, we report that the α5 nAChR subunit of the honey bee, Apis mellifera, when expressed in Xenopus laevis oocytes, has unusual pharmacological properties in that it has high sensitivity towards dopamine, tyramine and octopamine with EC50 values of 3.37 μM, 91.1 μM and 378 μM, respectively, whereas the EC50 for acetylcholine is 2.37 mM. The biogenic amines are also considerably more efficacious than acetylcholine in activating the receptor. Molecular dynamics simulations and expression of α5 mutants identify the lack of a proline doublet in loop E as playing a major role in determining dopamine efficacy. Together with phylogenetic analysis using homologous receptors from other species, this study enhances our understanding of how ligand-gated ion channels evolve functional diversity.

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