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

Accepted version
Peer-reviewed

Change log

Authors

Rievaj, Juraj 
O'Flaherty, Elisabeth A 
Smith, Christopher A 
Pais, Ramona 

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.

Description

Keywords

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

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

10

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MC_UU_12012/3)
Wellcome Trust (106262/Z/14/Z)
Wellcome Trust (100574/Z/12/Z)
Medical Research Council (MC_UU_12012/5)
Medical Research Council (MC_UU_12012/1)
Society for Endocrinology (Unknown)
BBSRC (1943916)
MRC (MC_UU_00014/3)
MRC (MC_UU_00014/5)
Medical Research Council (MC_PC_12012)
Wellcome Trust joint investigator award (106262/Z/14/Z and 106263/Z/14/Z); MRC programme within the Metabolic Diseases Unit (MRC_MC_UU_12012/3); MRC Metabolic Diseases Unit [MRC_MC_UU_12012/5] ; Wellcome Trust Strategic Award [100574/Z/12/Z]