[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.