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Central and peripheral role of the nociceptin/orphaninFQ system on normal and disturbed colonic motor function and faecal pellet output in the rat
Author(s) -
Broccardo M.,
Agostini S.,
Petrella C.,
Guerrini R.,
Improta G.
Publication year - 2008
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2008.01120.x
Subject(s) - nociceptin receptor , endocrinology , medicine , chemistry , antagonist , motility , agonist , peripheral , inhibitory postsynaptic potential , excretion , receptor , biology , opioid , opioid peptide , genetics
In this study, seeking further information on the role of the nociceptin/orphanin FQ (N/OFQ)‐ergic system in normal and disturbed colonic motor function in rats, we compared the colonic effects of UFP‐112, a novel highly potent agonist, with those of N/OFQ. When injected intracerebroventricularly (i.c.v.) and intraperitoneally (i.p.), UFP‐112 and N/OFQ increased bead expulsion time in a statistically significant and dose‐related manner and reduced the percentage of rats with castor oil‐induced diarrhoea. UFP‐112 showed greater efficacy, higher potency and longer‐lasting inhibitory effects than N/OFQ, and pretreatment with UFP‐101, a selective antagonist, blocked the N/OFQ analogue‐induced responses in both tests. When injected i.c.v., UFP‐112 and N/OFQ inhibited corticotrophin releasing factor‐ and restrain stress‐stimulated faecal pellet excretion significantly and in a dose‐related manner. Conversely, when injected peripherally both peptides significantly inhibited colonic propulsive motility but did so in a non‐dose‐related manner. In conclusion, these findings indicate that, in the rat, the central and peripheral N/OFQ systems have an inhibitory role in modulating distal colonic propulsive motility under physiological and pathological conditions. UFP‐112 therefore promises to be a useful pharmacological tool for investigating the role of the N/OFQ system in motor functions in the distal colonic tract under physiological and pathological conditions.