Alternative Pathways of Acetylcholine Release in the Colon : Role of High-Affinity Choline Transporters
Jiménez Farrerons, Marcel (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Martinez-Daunis, A. (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Yordanova, B. (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Traserra, S. (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Vergara, P. (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)

Data:	2026
Resum:	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.
Nota:	Altres ajuts: acords transformatius de la UAB
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Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Neurogastroenterology & motility, Vol. 38, Num. 3 (March 2026) , art. e70280, ISSN 1365-2982

DOI: 10.1111/nmo.70280

11 p, 821.6 KB

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