Alternative Pathways of Acetylcholine Release in the Colon
Background: Cholinergic neuromuscular transmission is central to gastrointestinal (GI) motility and is traditionally attributed to calcium-dependent, vesicular acetylcholine (ACh) release from enteric neurons. However, non-quantal, calcium-independent mechanisms-possibly involving transporter-mediat...
| Autores: | , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2026 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:dnet:uabarcelona_::d70af7611bb9e0d483ca423c5bf29142 |
| Acceso en línea: | https://ddd.uab.cat/record/327370 https://dx.doi.org/urn:doi:10.1111/nmo.70280 |
| Access Level: | acceso abierto |
| Sumario: | Background: Cholinergic neuromuscular transmission is central to gastrointestinal (GI) motility and is traditionally attributed to calcium-dependent, vesicular acetylcholine (ACh) release from enteric neurons. However, non-quantal, calcium-independent mechanisms-possibly involving transporter-mediated ACh efflux-may also contribute to cholinergic signaling. Aim: To investigate both classical and alternative mechanisms of ACh release in the colon, focusing on the potential role of non-vesicular, transporter-dependent pathways in modulating smooth muscle contractility. Methods: Experiments were performed on full-thickness and epithelium-depleted rat colonic muscle strips. Neostigmine, a reversible acetylcholinesterase inhibitor, was used to enhance cholinergic mechanisms. A panel of pharmacological agents-including tetrodotoxin (TTX selective blocker of Na channels), ω-conotoxin GVIA (Ca N-type channel blocker), Hemicholinium (choline transporter inhibitor), corticosterone (OCTs inhibitor), and hexamethonium (nicotinic receptor antagonist)-was applied to differentiate neural, non-neural, and transporter-mediated contributions to ACh release. Key Results: Neostigmine-induced contractions were preserved in epithelium-depleted strips, following neural blockade with TTX and ω-conotoxin GVIA. Hemicholinium concentration-dependently attenuated these contractions, suggesting involvement of high-affinity choline transporters operating in reverse mode. In contrast, corticosterone and hexamethonium had negligible effects, arguing against substantial roles for OCTs and nicotinic transmission. Conclusions and Inferences: These findings support the existence of a non-vesicular, transporter-dependent cholinergic signaling mechanism in the colon. This alternative pathway may contribute to the regulation of colonic motility and represents a novel target in GI motility modulation. |
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