Orphanin FQ/nociceptin and [Phe(1)Psi(CH2-NH)Gly(2)] nociceptin(1-13)-NH2 stimulate gastric motor function in anaesthetized rats

1 Orphanin FQ/nociceptin (OFQ/N) is a preferred endogenous ligand for the o rphan opioid receptor-like-1 receptor. This peptide has been reported to in crease intestinal, but not gastric, motor activity. 2 In the present study, OFQ/N (0.6-60 nmol kg(-1) i.v.) increased intragast ric pressure and antral contractility and, as expected, decreased blood pre ssure in anaesthetized rats. 3 The gastric motor effects of OFQ/N (6 nmol kg(-1)) were not affected by i nhibition of nitric oxide synthase or opioid receptor blockade. 4 OFQ/N (6 nmol kg(-1)) evoked gastric motor increases and hypotension were not affected by prior administration of its derivative [Phe(1)Psi(CH2-NH)G ly(2)]nociceptin-(1-13)-NH2 unless the pseudopepotide was administered shor tly (5 min) prior to OFQ/N. This putative antagonist (6-300 nmol kg(-1)) al one increased antral motility with approximately 100 fold lower potency tha n OFQ/N. 5 Neither bilateral vagotomy nor spinal cord transection altered OFQ/N-evok ed increases in intragastric pressure and antral contractility. 6 In conclusion, OFQ/N induces gastric motor excitation in addition to its known effects to increase intestinal motility. The gastric responses to OFQ /N are not dependent on 'classical' opioid receptor activation or nitric ox ide, similar to the case for the intestines. The primary site of action of OFQ/N on the stomach is probably via enteric nerves, since central descendi ng vagal or sympathetic pathways are not necessary for OFQ/N to increase ga stric motility. The gastric motor effects of the derivative [Phe(1)Psi(CH2- NH)Gly(2)]nociceptin-(1-13)-NH2 are similar to OFQ/N, although with lower p otency. The effects of the derivative as a partial agonist or antagonist in different experimental paradigms may reflect tissue OFQ/N receptor reserve .