Nociceptin, a novel endogenous ligand for the ORL1 receptor, dilates isolated resistance arteries from the rat

The heptadecapeptide nociceptin, also known as Orphanin FQ, is a recently d iscovered endogenous ligand for the opioid-like G-protein coupled receptor, ORL1. In the present study, responses to nociceptin were investigated in i solated pressurized resistance arteries from the rat mesenteric vascular be d. Nociceptin in bath concentrations of 10(-9)-10(-6) M induced concentrati on-dependent increases in arterial diameter when the artery was precontract ed with U46619; and administration of the structurally related opioid agoni sts, dynorphin A and met-enkephalin, had no effect on arterial diameter. Va sodilator responses to nociceptin were not altered by the opioid receptor a ntagonist naloxone or by the nitric oxide synthase inhibitor N-omega-nitro- L-arginine. Responses to nociceptin were not altered by the muscarinic rece ptor blocking agent atropine or phentolamine, or the calcitonin gene-relate d peptide (CGRP) receptor antagonist CGRP-(8-37). These data suggest that n ociceptin has direct vasodilator activity that is not dependent upon the ac tivation of a traditional opioid receptor, muscarinic or CGRP receptors, an inhibitory effect on the adrenergic nervous system, or the release of nitr ic oxide in isolated resistance arteries from the rat mesentery. (C) 1998 E lsevier Science BN. All rights reserved.