title: Dual Role of Endogenous Serotonin in 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis.
abstract: OBJECTIVE
  Changes in gut serotonin (5-HT) content have been described in Inflammatory Bowel Disease (IBD) and in different experimental models of colitis: the critical role of this monoamine in the pathogenesis of chronic gastrointestinal inflammation is gradually emerging. Aim of the present study was to evaluate the contribution of endogenous 5-HT through the activation of its specific receptor subtypes to the local and systemic inflammatory responses in an experimental model of IBD.
  
  
  METHODS
  Colitis was induced by intrarectal 2,4,6-TriNitroBenzene Sulfonic acid in mice subacutely treated with selective antagonists of 5-HT1A (WAY100135), 5-HT2A (Ketanserin), 5-HT3 (Ondansetron), 5-HT4 (GR125487), 5-HT7 (SB269970) receptors and with 5-HT1A agonist 8-Hydroxy-2-(di-n-propylamino)tetralin.
  
  
  RESULTS
  Blockade of 5-HT1A receptors worsened TNBS-induced local and systemic neutrophil recruitment while 5-HT1A agonist delayed and mitigated the severity of colitis, counteracting the increase in colonic 5-HT content. On the contrary, blockade of 5-HT2A receptors improved global health conditions, reduced colonic morphological alterations, down-regulated neutrophil recruitment, inflammatory cytokines levels and colonic apoptosis. Antagonism of 5-HT3, 5-HT4, and 5-HT7 receptor sites did not remarkably affect the progression and outcome of the pathology or only slightly improved it.
  
  
  CONCLUSIONS
  The prevailing deleterious contribution given by endogenous 5-HT to inflammation in TNBS-induced colitis is seemingly mediated by 5-HT2A and, to a lesser extent, by 5-HT4 receptors and coexists with the weak beneficial effect elicited by 5-HT1A stimulation. These findings suggest how only a selective interference with 5-HT pro-inflammatory actions may represent an additional potential therapeutic option for intestinal inflammatory disorders.
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Parma Parma, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Rapalli
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Parma Parma, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Bertoni
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Parma Parma, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Arcaro
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Parma Parma, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Saccani
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Parma Parma, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Grandi
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Parma Parma, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Vivo
authors.affiliation: Dipartimento di Scienze Medico-Veterinarie, Università degli Studi di Parma Parma, Italy.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Cantoni
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Parma Parma, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Barocelli
keywords: 5-HT1A receptor; 5-HT2A receptor; apoptosis; inflammation; intestine