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This Article Full Text Full Text (PDF) All Versions of this Article: 288/5/G1091    most recent 00302.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Porcher, C. Articles by Bonaz, B. Search for Related Content PubMed PubMed Citation Articles by Porcher, C. Articles by Bonaz, B.

NEUROREGULATION AND MOTILITY

Expression and effects of metabotropic CRF₁ and CRF₂ receptors in rat small intestine

¹Groupe d'Etude du Stress et des Interactions Neuro-Digestives, Equipe d’Accueil 3744, Department of Gastroenterology, Centre Hospitalier Universitaire de Grenoble, Grenoble; and ²Department of Radiobiology and Radiopathology, Centre de Recherches du Service de Santé des Armées, La Tronche, France

Submitted 9 July 2004 ; accepted in final form 4 January 2005

Corticotropin-releasing factor (CRF)-like peptides mediate their effects via two receptor subtypes, CRF₁ and CRF₂; these receptors have functional implication in the motility of the stomach and colon in rats. We evaluated expression and functions of CRF₁ and CRF₂ receptors in the rat small intestine (i.e., duodenum and ileum). CRF_1–2-like immunoreactivity (CRF_1–2-LI) was localized in fibers and neurons of the myenteric and submucosal ganglia. CRF_1–2-LI was found in nerve fibers of the longitudinal and circular muscle layers, in the mucosa, and in mucosal cells. Quantitative RT-PCR showed a stronger expression of CRF₂ than CRF₁ in the ileum, whereas CRF₁ expression was higher than CRF₂ expression in the duodenum. Functional studies showed that CRF-like peptides increased duodenal phasic contractions and reduced ileal contractions. CRF₁ antagonists (CP-154,526 and SSR125543Q) blocked CRF-like peptide-induced activation of duodenal motility but did not block CRF-like peptide-induced inhibition of ileal motility. In contrast, a CRF₂ inhibitor (astressin₂-B) blocked the effects of CRF-like peptides on ileal muscle contractions but did not influence CRF-like peptide-induced activation of duodenal motility. These results demonstrate the presence of CRF_1–2 in the intestine and demonstrate that, in vitro, CRF-like peptides stimulate the contractile activity of the duodenum through CRF₁ receptor while inhibiting phasic contractions of the ileum through CRF₂ receptor. These results strongly suggest that CRF-like peptides play a major role in the regulatory mechanisms that underlie the neural control of small intestinal motility through CRF receptors.

astressin₂-B; corticotropin-releasing factor receptors; urocortin

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