Orphanin FQ/nociceptin and [Phe1Ψ(CH2‐NH)Gly2] nociceptin(1‐13)‐NH2 stimulate gastric motor function in anaesthetized rats

Orphanin FQ/nociceptin (OFQ/N) is a preferred endogenous ligand for the orphan opioid receptor‐like‐1 receptor. This peptide has been reported to increase intestinal, but not gastric, motor activity. In the present study, OFQ/N (0.6–60 nmol kg−1 i.v.) increased intragastric pressure and antral contractility and, as expected, decreased blood pressure in anaesthetized rats. The gastric motor effects of OFQ/N (6 nmol kg−1) were not affected by inhibition of nitric oxide synthase or opioid receptor blockade. OFQ/N (6 nmol kg−1) evoked gastric motor increases and hypotension were not affected by prior administration of its derivative [Phe1Ψ(CH2‐NH)Gly2]nociceptin‐(1‐13)‐NH2 unless the pseudopepotide was administered shortly (5 min) prior to OFQ/N. This putative antagonist (6–300 nmol kg−1) alone increased antral motility with approximately 100 fold lower potency than OFQ/N. Neither bilateral vagotomy nor spinal cord transection altered OFQ/N‐evoked increases in intragastric pressure and antral contractility. 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 oxide, 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 descending vagal or sympathetic pathways are not necessary for OFQ/N to increase gastric motility. The gastric motor effects of the derivative [Phe1Ψ(CH2‐NH)Gly2]nociceptin‐(1‐13)‐NH2 are similar to OFQ/N, although with lower potency. The effects of the derivative as a partial agonist or antagonist in different experimental paradigms may reflect tissue OFQ/N receptor reserve. British Journal of Pharmacology (2000) 130, 1639–1645; doi:10.1038/sj.bjp.0703463