title: 5-HT7 receptors modulate peristalsis and accommodation in the guinea pig ileum.
abstract: OBJECTIVE
  The 5-hydroxytryptamine 7 (5-HT7) receptors mediate intestinal smooth muscle relaxation. In this study, we evaluated the expression of 5-HT7 receptors in the guinea pig ileum and their role in peristalsis and accommodation of the circular muscle.
  
  
  METHODS
  We used immunohistochemistry and confocal microscopy with whole tissue and cultured myenteric neurons. Peristalsis was induced by delivering a solution into the oral end of an isolated ileal segment. The effect of the selective 5-HT7 receptor antagonist SB-269970 (100 nmol/L) on peristaltic activity was evaluated at 30, 60, and 90 minutes and compared with control.
  
  
  RESULTS
  5-HT7 receptor immunoreactivity was localized to numerous myenteric neurons, a few submucosal neurons, and a few smooth muscle cells of the ileum. In enteric cultured neurons, 5-HT7 receptor immunoreactivity was observed in subpopulations of after hyperpolarizing neurons and descending neurons as identified by neuron-specific nuclear protein or calbindin and neuronal nitric oxide synthase or vasoactive intestinal peptide antibodies, respectively. SB-269970 significantly increased the threshold pressure by 33.3% +/- 2.2% (P < .001) and by 27.2% +/- 1.6% (P < .05) at 60 and 90 minutes, respectively, without modifying the threshold volume. The accommodation significantly decreased by 27.5% both at 60 and 90 minutes (P < .05).
  
  
  CONCLUSIONS
  Our results indicate that endogenous 5-HT is involved in the modulation of circular muscle accommodation during the preparatory phase of peristalsis via the activation of 5-HT7 receptors expressed by neurons in addition to smooth muscle cells. Overstimulation of these receptors leading to an exaggerated accommodation of circular muscle might contribute to abdominal symptoms in functional bowel disorders.
authors.affiliation: Department of Physiological and Pharmacological Sciences, University of Pavia, Pavia, Italy. marcello.tonini@unipv.it
authors.forename: Marcello
authors.initials: M
authors.lastname: Tonini
authors.forename: Riccardo
authors.initials: R
authors.lastname: Vicini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cervio
authors.forename: Fabrizio
authors.initials: F
authors.lastname: De Ponti
authors.forename: Roberto
authors.initials: R
authors.lastname: De Giorgio
authors.forename: Giovanni
authors.initials: G
authors.lastname: Barbara
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Stanghellini
authors.forename: Antonio
authors.initials: A
authors.lastname: Dellabianca
authors.forename: Catia
authors.initials: C
authors.lastname: Sternini
mesh_terms: D000818:Animals; D017615:Enteric Nervous System / Q000378:metabolism / Q000502:physiology*; D006168:Guinea Pigs; D007082:Ileum / Q000294:innervation / Q000502:physiology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D010528:Peristalsis / Q000187:drug effects / Q000502:physiology*; D010636:Phenols / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000378:metabolism / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D010636:Phenols; D011985:Receptors, Serotonin; C404922:SB 269970; D012702:Serotonin Antagonists; D013449:Sulfonamides; C104425:serotonin 7 receptor