Adenosine triphosphate is co-secreted with glucagon-like peptide-1 to modulate intestinal enterocytes and afferent neurons

Nat Commun. 2019 Mar 4;10(1):1029. doi: 10.1038/s41467-019-09045-9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Afferent Pathways
  • Animals
  • Cell Line
  • Eating
  • Enterocytes / metabolism*
  • Enteroendocrine Cells / metabolism
  • Female
  • Ganglion Cysts / metabolism
  • Ganglion Cysts / pathology
  • Glucagon-Like Peptide 1 / metabolism*
  • Incretins / metabolism
  • Intestinal Mucosa / innervation
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Intestines*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / pathology
  • Neurons, Afferent / metabolism*
  • Nodose Ganglion / metabolism
  • Nodose Ganglion / pathology
  • Peptide YY / metabolism
  • Receptors, Purinergic P2X2 / metabolism
  • Receptors, Purinergic P2X3 / metabolism
  • Vagus Nerve / metabolism

Substances

  • Incretins
  • Receptors, Purinergic P2X2
  • Receptors, Purinergic P2X3
  • Peptide YY
  • Glucagon-Like Peptide 1
  • Adenosine Triphosphate