title: PAR-2-mediated control of barrier function and motility differs between early and late phases of postinfectious gut dysfunction in the rat.
abstract: Proteinase-activated receptor-2 (PAR-2) and mast cell (MC) mediators contribute to inflammatory and functional gastrointestinal disorders. We aimed to characterize jejunal PAR-2-mediated responses and the potential MC involvement in the early and late phases of a rat model of postinfectious gut dysfunction. Jejunal tissues of control and Trichinella spiralis-infected (14 and 30 days postinfection) rats, treated or not with the MC stabilizer, ketotifen, were used. Histopathology and immunostaining were used to characterize inflammation, PAR-2 expression, and mucosal and connective tissue MCs. Epithelial barrier function (hydroelectrolytic transport and permeability) and motility were assessed in vitro in basal conditions and after PAR-2 activation. Intestinal inflammation on day 14 postinfection (early phase) was significantly resolved by day 30 (late phase) although MC counts and epithelial permeability remained increased. PAR-2-mediated ion transport (Ussing chambers, in vitro) and epithelial surface PAR-2 expression were reduced in the early phase, with a trend toward normalization during the late phase. In control conditions, PAR-2 activation (organ bath) induced biphasic motor responses (relaxation followed by excitation). At 14 days postinfection, spontaneous contractility and PAR-2-mediated relaxations were enhanced; motor responses were normalized on day 30. Postinfectious changes in PAR-2 functions were not affected by ketotifen treatment. We concluded that, in the rat model of Trichinella spiralis infection, alterations of intestinal PAR-2 function and expression depend on the inflammatory phase considered. A lack of a ketotifen effect suggests no interplay between MCs and PAR-2-mediated motility and ion transport alterations. These observations question the role of MC mediators in PAR-2-modulating postinfectious gut dysfunction.
authors.affiliation: Department of Cell Biology, Physiology and Immunology, Veterinary School, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Joan Antoni
authors.initials: JA
authors.lastname: Fernández-Blanco
authors.forename: Juan A
authors.initials: JA
authors.lastname: Fernández-Blanco
authors.forename: Morley D
authors.initials: MD
authors.lastname: Hollenberg
authors.forename: Vicente
authors.initials: V
authors.lastname: Martínez
authors.forename: Patri
authors.initials: P
authors.lastname: Vergara
mesh_terms: D000818:Animals; D005759:Gastroenteritis / Q000503:physiopathology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D041981:Gastrointestinal Tract / Q000503:physiopathology*; D007665:Ketotifen / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044464:Receptor, PAR-2 / Q000502:physiology*; D017160:Trichinella spiralis; D014235:Trichinellosis / Q000503:physiopathology*
chemical_list: D044464:Receptor, PAR-2; D007665:Ketotifen