Nociceptin receptor activation produces nitric oxide-mediated systemic hypotension.
The purpose of the present study was to investigate the effects of L-N5-(1-iminoethyl)ornithine hydrochloride (L-NIO), an inhibitor of nitric oxide (NO) formation, and [Phe1-psi(CH2NH)-Gly2]Nociceptin(1-13)-NH2 (Phe-NOC), a nociceptin receptor antagonist, on the systemic vasodepressor response to nociceptin in the anesthetized rat. The systemic vasodepressor response to bolus intravenous (i.v.) injections of nociceptin was significantly reduced by L-NIO and Phe-NOC. The present data suggest activation of nociceptin receptors dilates the systemic vascular bed through a NO-dependent pathway. These data also demonstrate Phe-NOC is an efficacious and selective nociceptin receptor antagonist in vivo.
Lin
B
B
H.L. Labs, Inc., New Orleans, LA 70112, USA.
Waterman
R
R
Lippton
H
H
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007022:Hypotension / Q000209:etiology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009292:Narcotic Antagonists; D009569:Nitric Oxide / Q000502:physiology*; D018847:Opioid Peptides / Q000494:pharmacology; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011957:Receptors, Opioid / Q000502:physiology*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D019331:NG-Nitroarginine Methyl Ester; D009292:Narcotic Antagonists; D009569:Nitric Oxide; D018847:Opioid Peptides; D009952:Ornithine; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C065027:N(G)-iminoethylornithine; C000722285:Oprl1 protein, rat