GPBA: A GPCR for bile acids and an emerging therapeutic target for disorders of digestion and sensation

Tina Marie Lieu, Gihan Jayaweera, Nigel William Bunnett

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Bile acids (BAs) are digestive secretions that are necessary for the emulsification and absorption of dietary fats. Given the episodic nature of BA secretion and intestinal re-absorption, the circulating and tissue levels of BAs, like those of the gut hormones, fluctuate in fasting and fed states, and BA levels and forms are markedly affected by disease. BAs exert widespread hormonal-like effects by activating receptors in the nucleus and at the plasma membrane. The nuclear steroid receptors mediate the genomic actions of BAs on BA, glucose and lipid homeostasis. GPBA (TGR5) is a G-protein coupled plasma membrane receptor for BAs that mediates many of the rapid, non-genomic actions of BAs. GPBA has been implicated in the control of glucose homeostasis, inflammation and liver functions. Recent observations have revealed an unexpected role for GPBA in the nervous system. GPBA is expressed by enteric neurons and enterochromaffin cells that control peristalsis, and GPBA mediates the prokinetic actions of BAs in the colon that have been known for millennia. GPBA is also present on primary spinal afferent and spinal neurons that are necessary for sensory transduction. BA-induced activation of GPBA in the sensory nervous system promotes scratching behaviours and analgesia, which may contribute to the pruritus and painless jaundice that are observed in some patients with chronic cholestatic disease, where circulating BA concentrations are markedly increased. Thus, GPBA has emerged as an intriguing target for diverse metabolic, inflammatory, digestive and sensory disorders, where agonists and antagonists may be of value.
Original languageEnglish
Pages (from-to)1156 - 1166
Number of pages11
JournalBritish Journal of Pharmacology
Volume171
Issue number5
DOIs
Publication statusPublished - 2014

Cite this

Lieu, Tina Marie ; Jayaweera, Gihan ; Bunnett, Nigel William. / GPBA: A GPCR for bile acids and an emerging therapeutic target for disorders of digestion and sensation. In: British Journal of Pharmacology. 2014 ; Vol. 171, No. 5. pp. 1156 - 1166.
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abstract = "Bile acids (BAs) are digestive secretions that are necessary for the emulsification and absorption of dietary fats. Given the episodic nature of BA secretion and intestinal re-absorption, the circulating and tissue levels of BAs, like those of the gut hormones, fluctuate in fasting and fed states, and BA levels and forms are markedly affected by disease. BAs exert widespread hormonal-like effects by activating receptors in the nucleus and at the plasma membrane. The nuclear steroid receptors mediate the genomic actions of BAs on BA, glucose and lipid homeostasis. GPBA (TGR5) is a G-protein coupled plasma membrane receptor for BAs that mediates many of the rapid, non-genomic actions of BAs. GPBA has been implicated in the control of glucose homeostasis, inflammation and liver functions. Recent observations have revealed an unexpected role for GPBA in the nervous system. GPBA is expressed by enteric neurons and enterochromaffin cells that control peristalsis, and GPBA mediates the prokinetic actions of BAs in the colon that have been known for millennia. GPBA is also present on primary spinal afferent and spinal neurons that are necessary for sensory transduction. BA-induced activation of GPBA in the sensory nervous system promotes scratching behaviours and analgesia, which may contribute to the pruritus and painless jaundice that are observed in some patients with chronic cholestatic disease, where circulating BA concentrations are markedly increased. Thus, GPBA has emerged as an intriguing target for diverse metabolic, inflammatory, digestive and sensory disorders, where agonists and antagonists may be of value.",
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GPBA: A GPCR for bile acids and an emerging therapeutic target for disorders of digestion and sensation. / Lieu, Tina Marie; Jayaweera, Gihan; Bunnett, Nigel William.

In: British Journal of Pharmacology, Vol. 171, No. 5, 2014, p. 1156 - 1166.

Research output: Contribution to journalArticleResearchpeer-review

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