Endogenous expression and in vitro study of CRF-related peptides and CRF receptors in the rat gastric antrum

In vivo studies suggest that corticotrophin-releasing factor (CRF) and CRF-like peptides, urocortin 1 (UCN 1) and UCN 2, inhibit gastric emptying and stimulate colonic motility through CRF2 and CRF1 receptors, respectively. We evaluated expression and functions of CRF, UCN 1, UCN 2 and CRF1 and CRF2 receptors in the rat gastric antrum. Tissues were processed for immunohistochemistry and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). In vitro studies were performed to test the functional significance of CRF, UCN 1 and UCN 2. Some experiments were realized in the presence of specific CRF1 or CRF2 receptors antagonists. CRF1 and CRF2 receptors-like immunoreactivity (CRF1 and CRF2 receptors-LI) was localized in fibers and neurons of the myenteric ganglia. CRF1 and CRF2 receptors-LI was also found in nerve fibers distributed in the muscle layers. CRF- and UCN 1-LI was observed in neuronal cell bodies of the myenteric ganglia and in numerous nerve fibers running parallel to smooth muscle cells. Quantitative RT-PCR demonstrated UCN 2, CRF1 and CRF2 receptors expressions in both muscle layers and mucosa of the gastric antrum. Functional studies showed that CRF, UCN 1 and UCN 2 decreased antral phasic contractions. CRF1 receptor antagonist (CP-154,526) did not block CRF-like peptides-induced inhibition of antral motility. In contrast, a CRF2 receptor antagonist (Astressin2-B) blocked the effects of CRF-like peptides on the antral muscle contractions. These results demonstrate (1) the presence of CRF, UCN and CRF1 and CRF2 receptors in the rat gastric antrum; (2) that, in vitro, CRF-like peptides inhibit phasic contractions of the antrum 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 gastric motility through CRF2 receptor.