Adenosine triphosphate is co-secreted with glucagon-like peptide-1 to modulate intestinal enterocytes and afferent neurons
| Autor: | Lu, Van B., Rievaj, Juraj, O’Flaherty, Elisabeth A., Smith, Christopher A., Pais, Ramona, Pattison, Luke A., Tolhurst, Gwen, Leiter, Andrew B., Bulmer, David C., Gribble, Fiona M., Reimann, Frank |
|---|---|
| Přispěvatelé: | Lu, Van B [0000-0002-4880-6455], Gribble, Fiona M [0000-0002-4232-2898], Reimann, Frank [0000-0001-9399-6377], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
endocrine system Enteroendocrine Cells Science Incretins Article Cell Line Eating Mice Adenosine Triphosphate Glucagon-Like Peptide 1 Animals Peptide YY Neurons Afferent Intestinal Mucosa lcsh:Science Ganglion Cysts Neurons Afferent Pathways digestive oral and skin physiology Vagus Nerve Intestines Mice Inbred C57BL Enterocytes lcsh:Q Female Nodose Ganglion Receptors Purinergic P2X3 hormones hormone substitutes and hormone antagonists Receptors Purinergic P2X2 |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-13 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Glucagon-like peptide 1 (GLP-1) is released from intestinal L-cells following nutrient uptake and enhances insulin release as well as promotes satiety. Here, the authors demonstrate that GLP-1 secreting cells release ATP and that this stimulates nodose neurons and enterocytes in a paracrine manner in vitro. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|