Expression and effects of metabotropic CRF₁and CRF₂receptors in rat small intestine

Abstract

Porcher, Christophe, Aurélie Juhem, André Peinnequin, Valé-rie Sinniger, and Bruno Bonaz. Expression and effects of metabotropic CRF1 and CRF2 receptors in rat small intestine. Am J Physiol Gastrointest Liver Physiol 288: G1091-G1103, 2005. First published January 6, 2005; doi:10.1152/ajpgi.00302.2004.-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). 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 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 CRF1-2 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 CORTICOTROPIN-RELEASING FACTOR (CRF) is a 41-amino acid peptide recognized as a major regulator of pituitary adrenocorticotropin (54). This neuropeptide is the principal mediator of a wide variety of physiological responses caused by sustained stresses (2, 9, 22, 51). The paraventricular nucleus (PVN) of the hypothalamus is the main source for CRF in the brain (49). Recently, the addition of three mammalian neuropeptides, urocortin (Ucn) 1, Ucn 2, and Ucn 3, have expanded the family of CRF-related peptides (18).The CRF-like peptides mediate their effects via two receptor subtypes, CRF 1 and CRF 2␣ /CRF 2␤ , each encoded by distinct genes (6,8,27,41). Both receptors belong to the seventransmembrane domain family positively coupled to adenylate cyclase via G proteins (1,3,12). CRF 1 receptor mRNA is predominantly expressed in the brain under basal conditions (4, 45) but is increased in the PVN in acute stress (4), somatovisceral pain (50), and colitis (42). The distribution of the CRF 2 receptor variants differs by ...

Expression of corticotropin-releasing factor and CRF receptors in micturition pathways after cyclophosphamide-induced cystitis

“…In contrast, neither CRF 1 receptor transcript nor CRF 1 receptor IR was expressed in bladder from control rats. In the small intestine, CRF 1-2 receptors were distributed within the neuronal elements of both nerve varicosities and nerve cell bodies in addition to epithelial cells (36). The CRF 2 receptor distribution in the small intestine (36) is consistent with the observations in the present study.…”

Corticotropin-releasing factor receptors and stress-related alterations of gut motor function

“…Peripheral CRF signaling and stress-related alterations of gut motor function As established for a number of neuropeptides (such as somatostatin, opiates, and calcitonin gene-related peptides) that act in the brain to influence gut motility (99), the CRF ligands and receptors that were initially characterized in the brain (where they function to influence gut motor function) have recently been shown to be widely expressed in peripheral tissues, including the gastrointestinal tract of experimental animals and humans (19,32,(100)(101)(102)(103). The coincident expression of CRF ligands, mostly urocortins, with cognate receptors provided strong support for the idea that their local action could influence gut motor function (100-102, 104, 105).…”

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“…At the level of the GI tract, stress delays gastric emptying through CRF2 while increasing colonic motility and secretion through CRF1 (Tache and Bonaz 2007). In the small bowel, CRF-like peptides stimulate the contractile activity of the duodenum through CRF1 receptor while inhibiting phasic contractions of the ileum through CRF2 receptor (Porcher, et al 2005).…”