[Tyr(1)]-nociceptin, a novel nociceptin analog, decreases systemic arterial pressure by a naloxone-insensitive mechanism in the rat

The heptadecapeptide nociceptin, also known as Or-phanin 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, [Tyr(1)]-nociceptin, were investigated in the systemic vascular bed of the rat. [Tyr(1)]-noeiceptin 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, [Tyr(1)]-nociceptin was comparable in potency to nociceptin. The decreases in systemic arterial pressure in response to [Tyr(1)]-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 [Tyr(1)]-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. (C) 1997 Academic Press.