Department of Medicine
Amino Acids, Peptides, and Proteins | Cell Biology | Cells | Digestive System | Hormones, Hormone Substitutes, and Hormone Antagonists | Nervous System
Enteroendocrine 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.
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DOI of Published Version
Nat Commun. 2019 Mar 4;10(1):1029. doi: 10.1038/s41467-019-09045-9. Link to article on publisher's site
Lu VB, Rievaj J, O'Flaherty EA, Smith CA, Pais R, Pattison LA, Tolhurst G, Leiter AB, Bulmer DC, Gribble FM, Reimann F. (2019). Adenosine triphosphate is co-secreted with glucagon-like peptide-1 to modulate intestinal enterocytes and afferent neurons. Open Access Articles. https://doi.org/10.1038/s41467-019-09045-9. Retrieved from https://escholarship.umassmed.edu/oapubs/3806
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.