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.