Contrary effects of the gut metabolites deoxycholate and butyrate on the acetylcholine-evoked calcium response in an enteroendocrine cell model
The interaction of nutrients and bacterial-derived products and their enteroendocrine effects are still enigmatic. We used the human enteroendocrine tumour cell line P-STS isolated from the terminal ileum as cellular sentinel. In this model, P-STS cells react to acetylcholine or histamine with an in...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-06-01
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| Series: | Endocrine and Metabolic Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666396124000116 |
| _version_ | 1797289648495525888 |
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| author | Beatrix Pfanzagl Erika Jensen-Jarolim |
| author_facet | Beatrix Pfanzagl Erika Jensen-Jarolim |
| author_sort | Beatrix Pfanzagl |
| collection | DOAJ |
| description | The interaction of nutrients and bacterial-derived products and their enteroendocrine effects are still enigmatic. We used the human enteroendocrine tumour cell line P-STS isolated from the terminal ileum as cellular sentinel. In this model, P-STS cells react to acetylcholine or histamine with an increase in intracellular calcium mediated by T-type voltage-gated calcium channels followed by serotonin secretion. Incubation with the secondary bile acid deoxycholate inhibited the calcium response to acetylcholine but not to histamine. No response to other nutrients or bacterial products tested (i.e. palmitate, lactate, acetate, proprionate, butyrate, the OR51E1 ligand isovalerate and the HCA2 ligand β-hydroxybutyrate) could be observed. The bile acid receptor TGR5 agonist CCDC did not inhibit the acetylcholine-induced calcium response, and the free fatty acid receptor 2 agonist 4-CMTB had no enhancing effect on the calcium response to acetylcholine. Only butyrate had an enhancing effect on the calcium response in P-STS cells when added for short-time pre-incubation before challenge with acetylcholine. From our data we propose i) an inhibitory effect of deoxycholate at the muscarinic acetylcholine receptor M3 without involvement of TGR5, and that ii) high butyrate concentrations derived from bacterial metabolism of carbohydrates might increase intestinal release of serotonin and potentially also other gut hormones and satiety-inducing peptides independently of known butyrate receptors, thereby influencing intestinal motility and ion secretion. |
| first_indexed | 2024-03-07T19:08:10Z |
| format | Article |
| id | doaj.art-3287a8d56c494fd296fcd2cbc891c102 |
| institution | Directory Open Access Journal |
| issn | 2666-3961 |
| language | English |
| last_indexed | 2024-03-07T19:08:10Z |
| publishDate | 2024-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Endocrine and Metabolic Science |
| spelling | doaj.art-3287a8d56c494fd296fcd2cbc891c1022024-03-01T05:07:21ZengElsevierEndocrine and Metabolic Science2666-39612024-06-0115100167Contrary effects of the gut metabolites deoxycholate and butyrate on the acetylcholine-evoked calcium response in an enteroendocrine cell modelBeatrix Pfanzagl0Erika Jensen-Jarolim1Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Austria; Corresponding author at: Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Währinger Gürtel 18-20, Vienna 1090, Austria.Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Austria; The Interuniversity Messerli Research Institute of the Univ. of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, AustriaThe interaction of nutrients and bacterial-derived products and their enteroendocrine effects are still enigmatic. We used the human enteroendocrine tumour cell line P-STS isolated from the terminal ileum as cellular sentinel. In this model, P-STS cells react to acetylcholine or histamine with an increase in intracellular calcium mediated by T-type voltage-gated calcium channels followed by serotonin secretion. Incubation with the secondary bile acid deoxycholate inhibited the calcium response to acetylcholine but not to histamine. No response to other nutrients or bacterial products tested (i.e. palmitate, lactate, acetate, proprionate, butyrate, the OR51E1 ligand isovalerate and the HCA2 ligand β-hydroxybutyrate) could be observed. The bile acid receptor TGR5 agonist CCDC did not inhibit the acetylcholine-induced calcium response, and the free fatty acid receptor 2 agonist 4-CMTB had no enhancing effect on the calcium response to acetylcholine. Only butyrate had an enhancing effect on the calcium response in P-STS cells when added for short-time pre-incubation before challenge with acetylcholine. From our data we propose i) an inhibitory effect of deoxycholate at the muscarinic acetylcholine receptor M3 without involvement of TGR5, and that ii) high butyrate concentrations derived from bacterial metabolism of carbohydrates might increase intestinal release of serotonin and potentially also other gut hormones and satiety-inducing peptides independently of known butyrate receptors, thereby influencing intestinal motility and ion secretion.http://www.sciencedirect.com/science/article/pii/S2666396124000116AcetylcholineButyrateDeoxycholateEnteroendocrineMuscarinic acetylcholine receptor M3Serotonin |
| spellingShingle | Beatrix Pfanzagl Erika Jensen-Jarolim Contrary effects of the gut metabolites deoxycholate and butyrate on the acetylcholine-evoked calcium response in an enteroendocrine cell model Endocrine and Metabolic Science Acetylcholine Butyrate Deoxycholate Enteroendocrine Muscarinic acetylcholine receptor M3 Serotonin |
| title | Contrary effects of the gut metabolites deoxycholate and butyrate on the acetylcholine-evoked calcium response in an enteroendocrine cell model |
| title_full | Contrary effects of the gut metabolites deoxycholate and butyrate on the acetylcholine-evoked calcium response in an enteroendocrine cell model |
| title_fullStr | Contrary effects of the gut metabolites deoxycholate and butyrate on the acetylcholine-evoked calcium response in an enteroendocrine cell model |
| title_full_unstemmed | Contrary effects of the gut metabolites deoxycholate and butyrate on the acetylcholine-evoked calcium response in an enteroendocrine cell model |
| title_short | Contrary effects of the gut metabolites deoxycholate and butyrate on the acetylcholine-evoked calcium response in an enteroendocrine cell model |
| title_sort | contrary effects of the gut metabolites deoxycholate and butyrate on the acetylcholine evoked calcium response in an enteroendocrine cell model |
| topic | Acetylcholine Butyrate Deoxycholate Enteroendocrine Muscarinic acetylcholine receptor M3 Serotonin |
| url | http://www.sciencedirect.com/science/article/pii/S2666396124000116 |
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