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1 Department of Gastroenterology, Groupe d'Etude du Stress et des Interactions Neuro-Digestives (GESIND, EA3744), Grenoble, France
2 Department of Radiobiology and Radio-Pathology, Centre de Recherches du Service de Sante des Armees, La Tronche, France
* To whom correspondence should be addressed. E-mail: christophe.porcher{at}ujf-grenoble.fr.
Corticotropin-releasing factor (CRF)-like peptides mediate their effects via two receptor subtypes, CRF1 and CRF2 receptors (CRF1-2); 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). CRF1-2 - like immunoreactivity (CRF1-2 - LI) was localized in fibers and neurons of the myenteric and submucosal ganglia. CRF1-2-LI was found in nerve fibers of the longitudinal and circular muscle layers, 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) block 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 the ileal muscle contractions, but did not influence CRF-like peptides induced activation of duodenal motility. These results demonstrate (1) the presence of CRF1-2 in the intestine; (2) that, in vitro, CRF-like peptides stimulate the contractile activity of the duodenum through CRF1 receptor while inhibit 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.
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