{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T14:06:34Z","timestamp":1780063594056,"version":"3.54.0"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T00:00:00Z","timestamp":1772841600000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cholinergic neuromuscular transmission is central to gastrointestinal (GI) motility and is traditionally attributed to calcium\u2010dependent, vesicular acetylcholine (ACh) release from enteric neurons. However, non\u2010quantal, calcium\u2010independent mechanisms\u2014possibly involving transporter\u2010mediated ACh efflux\u2014may also contribute to cholinergic signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To investigate both classical and alternative mechanisms of ACh release in the colon, focusing on the potential role of non\u2010vesicular, transporter\u2010dependent pathways in modulating smooth muscle contractility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Experiments were performed on full\u2010thickness and epithelium\u2010depleted rat colonic muscle strips. Neostigmine, a reversible acetylcholinesterase inhibitor, was used to enhance cholinergic mechanisms. A panel of pharmacological agents\u2014including tetrodotoxin (TTX selective blocker of Na\n                      <jats:sup>+<\/jats:sup>\n                      channels), \u03c9\u2010conotoxin GVIA (Ca\n                      <jats:sup>2+<\/jats:sup>\n                      <jats:italic>N<\/jats:italic>\n                      \u2010type channel blocker), Hemicholinium (choline transporter inhibitor), corticosterone (OCTs inhibitor), and hexamethonium (nicotinic receptor antagonist)\u2014was applied to differentiate neural, non\u2010neural, and transporter\u2010mediated contributions to ACh release.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Neostigmine\u2010induced contractions were preserved in epithelium\u2010depleted strips, following neural blockade with TTX and \u03c9\u2010conotoxin GVIA. Hemicholinium concentration\u2010dependently attenuated these contractions, suggesting involvement of high\u2010affinity choline transporters operating in reverse mode. In contrast, corticosterone and hexamethonium had negligible effects, arguing against substantial roles for OCTs and nicotinic transmission.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Inferences<\/jats:title>\n                    <jats:p>These findings support the existence of a non\u2010vesicular, transporter\u2010dependent 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nmo.70280","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T09:37:41Z","timestamp":1772962661000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Alternative Pathways of Acetylcholine Release in the Colon: Role of High\u2010Affinity Choline Transporters"],"prefix":"10.1111","volume":"38","author":[{"given":"A.","family":"Martinez\u2010Daunis","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Physiology and Immunology and Neurosciences Institute Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Yordanova","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Physiology and Immunology and Neurosciences Institute Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Traserra","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Physiology and Immunology and Neurosciences Institute Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Vergara","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Physiology and Immunology and Neurosciences Institute Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6602-7332","authenticated-orcid":false,"given":"M.","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Physiology and Immunology and Neurosciences Institute Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202000672R"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2024.176550"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006\u20103495(97)78806\u20104"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2009.050302"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2010.056440"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2015.08.007"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000535753"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100041\u20101740044"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15685"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000355835"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202101529R"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.03.036"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.03.023"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.04.018"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102982.2004.00603.x"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/2023.07.13.548886"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.33549\/physiolres.931865"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2012.03.031"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464\u2010410X.2006.05989.x"},{"key":"e_1_2_10_21_1","volume-title":"Cholinergic Tuft Cells and Their Role in Secretory Responses Across Species","author":"Mart\u00ednez\u2010Daunis A.","year":"2025"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2010.04.011"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704335"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476\u20105381.1986.tb10206.x"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2006.03.001"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.003"}],"container-title":["Neurogastroenterology &amp; 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