Lu, Van B.Rievaj, JurajO'Flaherty, Elisabeth A.Smith, Christopher A.Pais, RamonaPattison, Luke A.Tolhurst, GwenLeiter, Andrew B.Bulmer, David C.Gribble, Fiona M.Reimann, Frank2022-08-232022-08-232019-03-042019-05-16<p>Nat Commun. 2019 Mar 4;10(1):1029. doi: 10.1038/s41467-019-09045-9. <a href="https://doi.org/10.1038/s41467-019-09045-9">Link to article on publisher's site</a></p>2041-1723 (Linking)10.1038/s41467-019-09045-930833673https://hdl.handle.net/20.500.14038/41010Enteroendocrine cells are specialised sensory cells located in the intestinal epithelium and generate signals in response to food ingestion. Whilst traditionally considered hormone-producing cells, there is evidence that they also initiate activity in the afferent vagus nerve and thereby signal directly to the brainstem. We investigate whether enteroendocrine L-cells, well known for their production of the incretin hormone glucagon-like peptide-1 (GLP-1), also release other neuro-transmitters/modulators. We demonstrate regulated ATP release by ATP measurements in cell supernatants and by using sniffer patches that generate electrical currents upon ATP exposure. Employing purinergic receptor antagonists, we demonstrate that evoked ATP release from L-cells triggers electrical responses in neighbouring enterocytes through P2Y2 and nodose ganglion neurones in co-cultures through P2X2/3-receptors. We conclude that L-cells co-secrete ATP together with GLP-1 and PYY, and that ATP acts as an additional signal triggering vagal activation and potentially synergising with the actions of locally elevated peptide hormone concentrations.en-US© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.http://creativecommons.org/licenses/by/4.0/Amino Acids, Peptides, and ProteinsCell BiologyCellsDigestive SystemHormones, Hormone Substitutes, and Hormone AntagonistsNervous SystemJournal Articlehttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4820&amp;context=oapubs&amp;unstamped=1https://escholarship.umassmed.edu/oapubs/380614516657oapubs/3806