Role of serotonin in gastrointestinal physiology and pathology.
Serotonin is one of the most abundant molecules in the gastrointestinal tract and it plays a crucial role in the regulation of several physiological functions, such as motility, secretion and visceral sensitivity. Besides this well documented physiological role, increasing evidence supports the concept that 5-HT is directly involved in pathological mechanisms, as well as the modulation of immune/inflammatory responses within the gut. The wide range of pathophysiological actions exerted by 5-HT are mediated by several different serotonergic receptor types and subtypes. Depending on the receptor bound and its localization, 5-HT evokes different and, sometimes, opposite responses. Therapeutic interventions aiming at modulating 5-HT signaling are mainly focused on the development of receptor agonists/antagonists, characterized by high affinity and selectivity for serotonergic receptors in the gut, to avoid the presence of adverse effects in the brain, where 5-HT is important in control mood. This review summarizes the vast current knowledge on 5-HT as a physiological mediator and analyzes the increasing body of literature describing 5-HT signaling abnormalities in functional and inflammatory disorders both in animal models and in humans. Finally, an overview on the therapeutic agents used in clinical practice is provided.
Laboratory for Enteric Neuroscience (LENS), Leuven, Belgium 2 TARGID, KU Leuven, Leuven, Leuven, Belgium.
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Cirillo
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Vanden Berghe
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Tack
D000818:Animals; D003248:Constipation / Q000503:physiopathology; D004415:Dyspepsia / Q000503:physiopathology; D017615:Enteric Nervous System / Q000502:physiology; D005759:Gastroenteritis / Q000503:physiopathology; D005767:Gastrointestinal Diseases / Q000188:drug therapy / Q000503:physiopathology*; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D041981:Gastrointestinal Tract / Q000502:physiology*; D006801:Humans; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D043183:Irritable Bowel Syndrome / Q000503:physiopathology; D009474:Neurons / Q000502:physiology; D058748:Pain Perception / Q000502:physiology; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D050486:Serotonin Plasma Membrane Transport Proteins / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use; D014630:Vagus Nerve / Q000502:physiology; D059265:Visceral Pain / Q000503:physiopathology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; D012701:Serotonin