Neuro-humoral signalling by bile acids and the TGR5 receptor in the gastrointestinal tract

Nigel William Bunnett

Research output: Contribution to journalArticleResearchpeer-review

Abstract

In addition to their role in the digestion and absorption of dietary fats, bile acids (BAs) are tightly regulated signalling molecules. Their levels in the intestinal lumen, circulation and tissues fluctuate after feeding and fasting, and as a result of certain diseases and therapies. BAs regulate many cell types in the gut wall and beyond by activating nuclear and plasma membrane receptors. Of these, the G protein-coupled receptor TGR5 has emerged as a key mediator of the non-genomic actions of BAs. TGR5 is a cell-surface receptor that couples to Gas, formation of cAMP, activation of protein kinase A and extracellular signal-regulated kinases, and inhibition of inflammatory signalling pathways. TGR5 has been implicated in mediating the actions of BAs on secretion of glucagon-like peptide 1 and glucose homeostasis, gastrointestinal motility and transit, electrolyte and fluid transport in the colon, bile formation and secretion, sensory transduction and inflammation. TGR5 agonists have been developed as treatments for metabolic, inflammatory and digestive disorders, and emerging evidence suggests that TGR5 mutations are associated with inflammatory diseases. Thus, TGR5 plays an important role in the normal processes of digestion and is a new therapeutic target for important digestive diseases.
Original languageEnglish
Pages (from-to)2943 - 2950
Number of pages8
JournalThe Journal of Physiology
Volume592
Issue number14
DOIs
Publication statusPublished - 2014

Cite this

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title = "Neuro-humoral signalling by bile acids and the TGR5 receptor in the gastrointestinal tract",
abstract = "In addition to their role in the digestion and absorption of dietary fats, bile acids (BAs) are tightly regulated signalling molecules. Their levels in the intestinal lumen, circulation and tissues fluctuate after feeding and fasting, and as a result of certain diseases and therapies. BAs regulate many cell types in the gut wall and beyond by activating nuclear and plasma membrane receptors. Of these, the G protein-coupled receptor TGR5 has emerged as a key mediator of the non-genomic actions of BAs. TGR5 is a cell-surface receptor that couples to Gas, formation of cAMP, activation of protein kinase A and extracellular signal-regulated kinases, and inhibition of inflammatory signalling pathways. TGR5 has been implicated in mediating the actions of BAs on secretion of glucagon-like peptide 1 and glucose homeostasis, gastrointestinal motility and transit, electrolyte and fluid transport in the colon, bile formation and secretion, sensory transduction and inflammation. TGR5 agonists have been developed as treatments for metabolic, inflammatory and digestive disorders, and emerging evidence suggests that TGR5 mutations are associated with inflammatory diseases. Thus, TGR5 plays an important role in the normal processes of digestion and is a new therapeutic target for important digestive diseases.",
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Neuro-humoral signalling by bile acids and the TGR5 receptor in the gastrointestinal tract. / Bunnett, Nigel William.

In: The Journal of Physiology, Vol. 592, No. 14, 2014, p. 2943 - 2950.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

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AB - In addition to their role in the digestion and absorption of dietary fats, bile acids (BAs) are tightly regulated signalling molecules. Their levels in the intestinal lumen, circulation and tissues fluctuate after feeding and fasting, and as a result of certain diseases and therapies. BAs regulate many cell types in the gut wall and beyond by activating nuclear and plasma membrane receptors. Of these, the G protein-coupled receptor TGR5 has emerged as a key mediator of the non-genomic actions of BAs. TGR5 is a cell-surface receptor that couples to Gas, formation of cAMP, activation of protein kinase A and extracellular signal-regulated kinases, and inhibition of inflammatory signalling pathways. TGR5 has been implicated in mediating the actions of BAs on secretion of glucagon-like peptide 1 and glucose homeostasis, gastrointestinal motility and transit, electrolyte and fluid transport in the colon, bile formation and secretion, sensory transduction and inflammation. TGR5 agonists have been developed as treatments for metabolic, inflammatory and digestive disorders, and emerging evidence suggests that TGR5 mutations are associated with inflammatory diseases. Thus, TGR5 plays an important role in the normal processes of digestion and is a new therapeutic target for important digestive diseases.

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