Contributions of bile acids to gastrointestinal physiology as receptor agonists and modifiers of ion channels

Author:

Keely Stephen J.1,Urso Andreacarola23,Ilyaskin Alexandr V.4,Korbmacher Christoph4ORCID,Bunnett Nigel W.56,Poole Daniel P.78ORCID,Carbone Simona E.78ORCID

Affiliation:

1. Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland

2. Department of Surgery, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York

3. Department of Pharmacology, Columbia University, New York, New York

4. Institute of Cellular and Molecular Physiology, Friedrich-Alexander University Erlangen-Nürnberg, Bavaria, Germany

5. Department of Molecular Pathobiology, Neuroscience Institute, New York University, New York, New York

6. Department of Neuroscience and Physiology, Neuroscience Institute, New York University, New York, New York

7. Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia

8. Australian Research Council, Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia

Abstract

Bile acids (BAs) are known to be important regulators of intestinal motility and epithelial fluid and electrolyte transport. Over the past two decades, significant advances in identifying and characterizing the receptors, transporters, and ion channels targeted by BAs have led to exciting new insights into the molecular mechanisms involved in these processes. Our appreciation of BAs, their receptors, and BA-modulated ion channels as potential targets for the development of new approaches to treat intestinal motility and transport disorders is increasing. In the current review, we aim to summarize recent advances in our knowledge of the different BA receptors and BA-modulated ion channels present in the gastrointestinal system. We discuss how they regulate motility and epithelial transport, their roles in pathogenesis, and their therapeutic potential in a range of gastrointestinal diseases.

Funder

University of Erlangen-Nuremberg

Department of Health, Australian Government | NHMRC | National Institute for Dementia Research

HHS | NIH | National Institute of Neurological Disorders and Stroke

HHS | NIH | National Institute of Dental and Craniofacial Research

HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases

Science Foundation Ireland

U.S. Department of Defense

Australian Research Council

Publisher

American Physiological Society

Subject

Physiology (medical),Gastroenterology,Hepatology,Physiology

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