Peripheral corticotropin-releasing factor and stress-stimulated colonic motor activity involve type 1 receptor in rats

Background & Aims: Corticotropin-releasing factor (CRF) exerts its action through CRF receptors 1 and 2 (CRF-R1 and CRF-R2). CRF has preferential affinity for CRF-R1, whereas urocortin displays high affinity for both. We investigated changes in colonic motor function after intraperitoneal (IP) injection of CRF-related peptides. Methods: Colonic motility was recorded in vivo in conscious vats equipped with electrodes chronically implanted in the cecum and proximal colon or in vitro in distal colon; fecal output was monitored in naive rats. Results: Rat CRF, rat urocortin, and amphibian sauvagine (10 mug/kg, IP) induced a new pattern of cecocolonic myoelectric activity characterized by clustered spike bursts of long duration; the percentage of occurrence was highest after CRF. The rank order of potency tb increase fecal pellet output after IP peptide injection (0.3-10 mug/kg, IF) was CRF > urocortin = sauvagine. The CRF-R1/R2 antagonist astressin (33 mug/kg, IF) and the CRF-R1 antagonist CP-154,526 (20 mg/kg, subcutaneously) inhibited IP CRF-induced changes in cecocolonic myoelectric activity and IP CRF and water avoidance stress-induced fecal output. In vitro, CRF injected into the inferior mesenteric artery increased distal colonic myoelectric activity compared with saline injection. Conclusions: These results demonstrate that CRF acts peripherally to stimulate colonic motility and that CRF-RI is primarily involved in mediating IP CRF/urocortin- and water avoidance stress-induced colonic motor response.