Urocortin I is present in the enteric nervous system and exerts an excitatory effect via cholinergic and serotonergic pathways in the rat colon.
Corticotropin-releasing factor (CRF) and urocortin I (UcnI) have been shown to accelerate colonic transit after central nervous system (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, and 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 exerted 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, as well as 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.
Kimura
Takazumi
T
Division of Gastroenterology, National Center of Neurology and Psychiatry, Kohnodai Hospital, Chiba 272-8516, Japan.
Amano
Tomofumi
T
Uehara
Hirotsugu
H
Ariga
Hajime
H
Ishida
Tsuyoshi
T
Torii
Akira
A
Tajiri
Hisao
H
Matsueda
Kei
K
Yamato
Shigeru
S
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003106:Colon / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004558:Electric Stimulation; D017615:Enteric Nervous System / Q000378:metabolism*; D005769:Gastrointestinal Motility; D018738:Hexamethonium / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D017294:Ondansetron / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000032:analysis; D058831:Serotonin 5-HT3 Receptor Antagonists; D058832:Serotonin 5-HT4 Receptor Antagonists; D013779:Tetrodotoxin / Q000494:pharmacology; D054832:Urocortins / Q000378:metabolism*
D004146:Dioxanes; D010446:Peptide Fragments; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; D058831:Serotonin 5-HT3 Receptor Antagonists; D058832:Serotonin 5-HT4 Receptor Antagonists; D054832:Urocortins; C103016:antalarmin; C120841:astressin B; C084858:SB 204070A; D018738:Hexamethonium; D013779:Tetrodotoxin; D017294:Ondansetron; D001285:Atropine; D003346:Corticotropin-Releasing Hormone; D019331:NG-Nitroarginine Methyl Ester