Central and peripheral role of the nociceptin/orphaninFQ system on normal and disturbed colonic motor function and faecal pellet output in the rat.
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.
Broccardo
M
M
Department of Human Physiology and Pharmacology "V. Erspamer", University of Rome "Sapienza", Rome, Italy. maria.broccardo@uniroma1.it
Agostini
S
S
Petrella
C
C
Guerrini
R
R
Improta
G
G
D000818:Animals; D002368:Castor Oil / Q000494:pharmacology; D002400:Cathartics / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005243:Feces; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D005772:Gastrointestinal Transit / Q000187:drug effects / Q000502:physiology; D008297:Male; D018847:Opioid Peptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013315:Stress, Psychological; D014665:Vasodilator Agents / Q000378:metabolism; D000097629:Nociceptin
D002368:Castor Oil; D002400:Cathartics; D003346:Corticotropin-Releasing Hormone; D018847:Opioid Peptides; D014665:Vasodilator Agents; D000097629:Nociceptin; C479838:(Nphe(1),Arg(14),Lys(15))N-OFQ NH(2)