title: Neuronal serotonin regulates growth of the intestinal mucosa in mice.
abstract: OBJECTIVE
  The enteric abundance of serotonin (5-HT), its ability to promote proliferation of neural precursors, and reports that 5-HT antagonists affect crypt epithelial proliferation led us to investigate whether 5-HT affects growth and maintenance of the intestinal mucosa in mice.
  
  
  METHODS
  cMice that lack the serotonin re-uptake transporter (SERTKO mice) and wild-type mice were given injections of selective serotonin re-uptake inhibitors (gain-of-function models). We also analyzed mice that lack tryptophan hydroxylase-1 (TPH1KO mice, which lack mucosal but not neuronal 5-HT) and mice deficient in tryptophan hydroxylase-2 (TPH2KO mice, which lack neuronal but not mucosal 5-HT) (loss-of-function models). Wild-type and SERTKO mice were given ketanserin (an antagonist of the 5-HT receptor, 5-HT(2A)) or scopolamine (an antagonist of the muscarinic receptor). 5-HT(2A) receptors and choline acetyltransferase were localized by immunocytochemical analysis.
  
  
  RESULTS
  Growth of the mucosa and proliferation of mucosal cells were significantly greater in SERTKO mice and in mice given selective serotonin re-uptake inhibitors than in wild-type mice, but were diminished in TPH2KO (but not in TPH1KO) mice. Ketanserin and scopolamine each prevented the ability of SERT knockout or inhibition to increase mucosal growth and proliferation. Cholinergic submucosal neurons reacted with antibodies against 5-HT(2A).
  
  
  CONCLUSIONS
  5-HT promotes growth and turnover of the intestinal mucosal epithelium. Surprisingly, these processes appear to be mediated by neuronal, rather than mucosal, 5-HT. The 5-HT(2A) receptor activates cholinergic neurons, which provide a muscarinic innervation to epithelial effectors.
authors.affiliation: College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Erica R
authors.initials: ER
authors.lastname: Gross
authors.forename: Michael D
authors.initials: MD
authors.lastname: Gershon
authors.forename: Kara G
authors.initials: KG
authors.lastname: Margolis
authors.forename: Zoya V
authors.initials: ZV
authors.lastname: Gertsberg
authors.forename: Zhishan
authors.initials: Z
authors.lastname: Li
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cowles
mesh_terms: D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D059329:Cholinergic Neurons / Q000378:metabolism*; D004759:Enterochromaffin Cells / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000254:growth & development* / Q000378:metabolism; D007650:Ketanserin / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018727:Muscarinic Antagonists / Q000008:administration & dosage; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D012601:Scopolamine / Q000008:administration & dosage; D059326:Serotonergic Neurons / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D012702:Serotonin Antagonists / Q000008:administration & dosage; D050486:Serotonin Plasma Membrane Transport Proteins / Q000172:deficiency; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000172:deficiency
chemical_list: D002795:Choline O-Acetyltransferase; D007650:Ketanserin; D018727:Muscarinic Antagonists; D044402:Receptor, Serotonin, 5-HT2A; D012601:Scopolamine; D012701:Serotonin; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D014365:Tryptophan Hydroxylase; C487801:Tph1 protein, mouse; C487802:Tph2 protein, mouse