Orphanin FQ/nociceptin and [Phe(1)Psi(CH(2)-NH)Gly(2)] nociceptin(1-13)-NH(2) 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 [Phe(1)Psi(CH(2)-NH)Gly(2)]nociceptin-(1-13)-NH(2) 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 [Phe(1)Psi(CH(2)-NH)Gly(2)]nociceptin-(1-13)-NH(2) 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.
Krowicki
Z K
ZK
Louisiana State University Health Sciences Center, Department of Pharmacology and Center of Excellence for Neuroscience, 1901 Perdido Street, New Orleans, Louisiana, LA 70112, USA. zkrowi@lsumc.edu
Kapusta
D R
DR
Hornby
P J
PJ
D000758:Anesthesia; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018847:Opioid Peptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000601:surgery; D013119:Spinal Cord Injuries; D014628:Vagotomy / Q000009:adverse effects; D000097629:Nociceptin
D004791:Enzyme Inhibitors; D019331:NG-Nitroarginine Methyl Ester; D009270:Naloxone; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010446:Peptide Fragments; D000097629:Nociceptin; C114149:nociceptin (1-13)-NH2, Phe(1)-psi(CH2-NH)-Gly(2)-