Non-conventional features of peripheral serotonin signalling — the gut and beyond

Key Points Serotonin is an important molecule that was first discovered in the gut and contributes to the activation of intrinsic and extrinsic gastrointestinal reflexes Enterochromaffin cells are the major source of serotonin in the gut and in platelets, but we now know that serotonin is also synthesized in other peripheral tissues Serotonin synthesis and release by enterochromaffin cells is influenced by gut microorganisms via the generation of short-chain fatty acids In the intestinal mucosa, serotonin can act to promote inflammation, but also to protect from and reverse inflammation through activation of dendritic cell 5-HT 7 receptors and epithelial 5-HT 4 receptors, respectively Serotonin influences metabolic homeostasis through actions in pancreatic islets, in the liver and in adipose tissue Within bone, serotonin acts both in the bone marrow to stimulate haematopoiesis and also in osseous tissue to influence bone metabolism