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Evidence for the presence of functional protease activated receptor 4 (PAR4) in the rat colon.
Mulè, F; Pizzuti, R; Capparelli, A; Vergnolle, N.
Afiliación
  • Mulè F; Dipartimento di Biologia cellulare e dello Sviluppo, Laboratorio di Fisiologia Generale, Università di Palermo, Viale delle Scienze, 90128 Palermo, Italy. fmule@unipa.it
Gut ; 53(2): 229-34, 2004 Feb.
Article en En | MEDLINE | ID: mdl-14724155
BACKGROUND AND AIMS: Protease activated receptors (PARs) have been postulated to play a role during intestinal inflammation. The presence and role played by PAR(4) in gastrointestinal functions have not been fully clarified. The aims of this study were: (i) to examine expression of PAR(4) in rat proximal colon; (ii) to determine the mechanical effects induced by PAR(4) activation in longitudinal muscle; and (iii) to characterise the underlying mechanisms. METHODS: PAR(4) expression was determined by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Mechanical activity was recorded as changes in isometric tension. RESULTS: A PCR product corresponding to the predicted size of the PAR(4) signal was amplified from RNA prepared from the colon of rats, showing the presence of PAR(4) in those tissues. Immunohistochemistry revealed that PAR(4) protein was expressed on epithelial surfaces and submucosa. PAR(4) activating peptides, GYPGKF-NH(2) and AYPGKG-NH(2), produced concentration dependent contractile effects on longitudinal muscle. Tetrodotoxin (TTX) or atropine significantly reduced the contractile responses to AYPGKG-NH(2), and atropine after TTX did not cause any further reduction. NK(1) receptor antagonist, SR140333, or NK(2) receptor antagonist, SR48968, alone or in combination, produced a reduction in PAR(4) induced contractile effect, and when coadministered with TTX abolished it. Capsaicin markedly reduced the contractions evoked by AYPGKG-NH(2). CONCLUSIONS: The present results suggest that PAR(4) is functionally expressed in rat colon and its activation induces contraction of the longitudinal muscle both through TTX sensitive release of acetylcholine and release of tachykinins, probably from sensory nerves. These actions may contribute to motility disturbances during intestinal trauma and inflammation.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Trombina / Colitis / Colon Límite: Animals Idioma: En Revista: Gut Año: 2004 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Trombina / Colitis / Colon Límite: Animals Idioma: En Revista: Gut Año: 2004 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido