title: Serotonin is a sword and a shield of the bowel: serotonin plays offense and defense.
abstract: The gut contains the bulk of the body's serotonin (5-hydroxytryptamine, 5-HT); nevertheless, the physiological role that enteric 5-HT plays has not been determined. 5-HT is linked to gastrointestinal (GI) motility; increased intraluminal pressure causes enterochromaffin (EC) cells to secrete 5-HT, which stimulates intrinsic primary afferent neurons that initiate peristaltic reflexes. 5-HT is also an enteric neurotransmitter. Surprisingly, deletion of tryptophan hydroxylase-1 (TPH1), upon which 5-HT biosynthesis in EC cells depends, does not alter constitutive GI motility, whereas deletion of TPH2, upon which biosynthesis of neuronal 5-HT depends, slows intestinal transit and accelerates gastric emptying. TPH1 deletion, however, protects mice from experimental inflammation; 5-HT potentiation and TPH2 deletion each make inflammation more severe. Neuronal 5-HT is neuroprotective and recruits stem cells to give rise to new enteric neurons in adult mice. Mucosal 5-HT, therefore, may mobilize inflammatory effectors, which protect the gut from invasion, whereas neuronal 5-HT shields enteric neurons from inflammatory damage.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, P&S, 630 West 168th Street, New York, NY 10032, USA. mdg4@columbia.edu
authors.forename: Michael D
authors.initials: MD
authors.lastname: Gershon
mesh_terms: D000818:Animals; D017615:Enteric Nervous System / Q000166:cytology / Q000502:physiology*; D004759:Enterochromaffin Cells / Q000166:cytology / Q000502:physiology; D005756:Gastritis / Q000503:physiopathology*; D005769:Gastrointestinal Motility / Q000502:physiology; D041981:Gastrointestinal Tract / Q000166:cytology / Q000294:innervation* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D055495:Neurogenesis / Q000502:physiology*; D059326:Serotonergic Neurons / Q000166:cytology / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D014365:Tryptophan Hydroxylase / Q000172:deficiency / Q000235:genetics / Q000502:physiology
chemical_list: D012701:Serotonin; C487801:Tph1 protein, mouse; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase