Submitted on February 7, 2007
Accepted on August 8, 2007
Urocortin I is present in the enteric nervous system and exerts an excitatory effect via cholinergic and serotonergic pathways in the rat colon
Takazumi Kimura1, Tomofumi Amano2, Hirotsugu Uehara3, Hajime Ariga2, Tsuyoshi Ishida4, Akira Torii1, Hisao Tajiri1, Kei Matsueda5, and Shigeru Yamato2*
1 Division of Gastroenterology and Hepatology, Jikei University School of Medicine, minato-ku, Tokyo, Japan
2 Division of Gastroenterology, National Center of Neurology and Psychiatry, Kohnodai Hospital, Ichikawa, Chiba, Japan
3 Ichikawa, Chiba, Japan; Division of Gastroenterology, National Center of Neurology and Psychiatry, Kohnodai Hospital, Ichikawa, Chiba, Japan
4 Division of Pathology, National Center of Neurology and Psychiatry, Kohnodai Hospital, Ichikawa, Japan
5 Saigata Hospital, Johetsu, Niigata, Japan
* To whom correspondence should be addressed. E-mail: dsyamato{at}ncnpk2.hosp.go.jp.
Corticotropin-releasing factor (CRF) and urocortin I (UcnI) have been shown to accelerate colonic transit after CNS or peripheral administration, but the mechanism of their peripheral effect on colonic motor function has not been fully investigated. Furthermore, the localization of UcnI in the enteric nervous system (ENS) of the colon is unknown. We investigated the effect of CRF and UcnI on colonic motor function and examined the localization of CRF, UcnI, CRF receptors, choline acetyltransferase (ChAT) and 5-HT. Isometric tension of rat colonic muscle strips was measured. The effect of CRF, UcnI on phasic contractions and electrical field stimulation (EFS)-induced off-contractions were examined. The effects of UcnI on both types of contraction were also studied in the presence of antalarmin, astressin2-B, tetrodotoxin (TTX), atropine, 5-HT antagonists. The localizations of CRF, UcnI, CRF receptors, ChAT and 5-HT in the colon were investigated by immunohistochemistry. CRF and UcnI increased both contractions dose-dependently. UcnI exerting a more potent effect than CRF. Antalarmin, TTX, atropine, and 5-HT antagonists abolished the contractile effects of UcnI. CRF and UcnI were observed in the neuronal cells of the myenteric plexus. UcnI and ChAT, and UcnI and 5-HT, were colocalized in some of the neuronal cells of the myenteric plexus. This study demonstrated that CRF and UcnI act on the ENS and increase colonic contractility by enhancing cholinergic and serotonergic neurotransmission. These peptides are present in myenteric neurons. CRF and, perhaps to a greater extent, UcnI appear to act as neuromodulators in the ENS of the rat colon.
