Expression and effects of metabotropic CRF1and CRF2receptors in rat small intestine

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Abstract
Corticotropin-releasing factor (CRF)-like peptides mediate their effects via two receptor subtypes, CRF1and CRF2; these receptors have functional implication in the motility of the stomach and colon in rats. We evaluated expression and functions of CRF1and CRF2receptors 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, in the mucosa, and in mucosal cells. Quantitative RT-PCR showed a stronger expression of CRF2than CRF1in the ileum, whereas CRF1expression was higher than CRF2expression in the duodenum. Functional studies showed that CRF-like peptides increased duodenal phasic contractions and reduced ileal contractions. CRF1antagonists (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 CRF2inhibitor (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 CRF1–2in the intestine and demonstrate that, in vitro, CRF-like peptides stimulate the contractile activity of the duodenum through CRF1receptor while inhibiting phasic contractions of the ileum through CRF2receptor. 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.