The effect of urocortin 1 on motility in isolated, vascularly perfused rat colon.

BACKGROUND/AIMS: Urocortin 1, a corticotropin-releasing factor related peptide, increases colonic motility under stressful conditions. We investigated the effect of urocortin 1 on colonic motility using an experimental model with isolated rat colon in which the blood flow and intestinal nerves were preserved. Furthermore, we assessed whether this effect was mediated by adrenergic or cholinergic nerves.

METHODS

Colonic motility was measured in the proximal and distal parts of resected rat colon. The colon resected from the peritoneum was stabilized, and then urocortin 1 (13.8, 138, 277, and 1,388 pM) was administered via a blood vessel. Motility index was measured in the last 5 min of the 15 min administration of urocortin 1 and expressed as percentage change from baseline. Subsequently, the change in motility was measured by perfusing urocortin 1 in colons pretreated with phentolamine, propranolol, hexamethonium, atropine, or tetrodotoxin.

RESULTS

At concentrations of 13.8, 138, 277, and 1,388 pM, urocortin 1 increased the motility of proximal colon (20.4 ± 7.2%,48.4 ± 20.9%, 67.0 ± 25.8%, and 64.2 ± 20.9%, respectively) and the motility of distal colon (3.3 ± 3.3%, 7.8 ± 7.8%, 71.1 ± 28.6%,and 87.4 ± 32.5%, respectively). The motility induced by urocortin 1 was significantly decreased by atropine to 2.4 ± 2.4% in proximal colon and 3.4 ± 3.4% in distal colon (p <œ 0.05). However, tetrodotoxin, propranolol, phentolamine, and hexamethonium did not inhibit motility.

CONCLUSIONS

Urocortin 1 increased colonic motility and it is considered that this effect was directly mediated by local muscarinic cholinergic receptors.