Gastrointestinal effects of intracerebroventricularly injected nociceptin/orphaninFQ in rats.
Nociceptin/orphanin FQ/(N/OFQ), a novel heptadecapeptide recently isolated from porcine and rat brain, is the endogenous ligand of the N/OFQ peptide receptor (NOP, previously known as ORL-1). In this study we examined the effects of intracerebroventricularly (icv) injected N/OFQ on gastric emptying, gastrointestinal transit, colonic propulsion and gastric acid secretion in rats. N/OFQ (0.01-10 nmol/rat) significantly delayed gastric emptying of a phenol red meal, inhibited transit of a non-absorbable charcoal marker through the small intestine and increased the mean colonic bead expulsion time. These N/OFQ-motor effects were abolished by the NOP receptor selective antagonist [NPhe(1)]N/OFQ(1-13)-NH(2) (50 nmol/rat), but were unaltered by the classical opioid receptor antagonist, naloxone (9.2 micromol/kg). Icv injected N/OFQ (10 nmol/rat) decreased gastric acid secretion in 2-h pylorus ligated rats in a naloxone sensitive manner. [NPhe(1)]N/OFQ(1-13)-NH(2) (100 nmol/rat) icv administered alone stimulated gastric acid secretion. These results indicate that N/OFQ activates via NOP receptor stimulation a central inhibitory pathway modulating gastrointestinal propulsive activity and gastric acid secretion in rats.
Broccardo
Maria
M
Department of Human Physiology and Pharmacology, University "La Sapienza" Ple A. Moro 5-00185, Rome, Italy.
Guerrini
Remo
R
Petrella
Carla
C
Improta
Giovanna
G
D000818:Animals; D005744:Gastric Acid / Q000378:metabolism; D005746:Gastric Emptying / Q000187:drug effects; D041981:Gastrointestinal Tract / Q000187:drug effects*; D005772:Gastrointestinal Transit / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D009270:Naloxone; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C403776:nociceptin-(1-13)-NH2, NPhe(1)-; C000722285:Oprl1 protein, rat