[Tyr1]-nociceptin, a novel nociceptin analog, decreases systemic arterial pressure by a naloxone-insensitive mechanism in the rat.
The heptadecapeptide nociceptin, also known as Orphanin FQ, is a newly discovered endogenous ligand for the opioid-like G-protein-coupled receptor ORL1. In the present study, responses to a novel nociceptin analog, [Tyr1]-nociceptin, were investigated in the systemic vascular bed of the rat. [Tyr1]-nociceptin induced dose-related decrease in systemic arterial pressure when injected in doses of 1-30 nmol/kg i.v. In terms of relative vasodepressor activity, [Tyr1]-nociceptin was comparable in potency to nociceptin. The decreases in systemic arterial pressure in response to [Tyr1]-nociceptin were not altered by the opioid receptor antagonist naloxone in a dose that reduced responses to Met-enkephalin. The results of the present study show that vasodepressor responses to [Tyr1]-nociceptin are not mediated by the activation of a naloxone-sensitive opioid receptor and are not dependent on the presence of Phe at the N-terminus of the nociceptin sequence.
Champion
H C
HC
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Kadowitz
P J
PJ
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects*; D004744:Enkephalin, Methionine / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D008024:Ligands; D008297:Male; D008969:Molecular Sequence Data; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018847:Opioid Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists* / Q000378:metabolism; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D004744:Enkephalin, Methionine; D008024:Ligands; D009270:Naloxone; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C106528:nociceptin, Tyr(1)-; C000722285:Oprl1 protein, rat