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

• Published in: Regulatory peptides 1998-11, Vol.78 (1-3), p.69-74
• Main Authors: CHAMPION, H. C, PIERCE, R. L, KADOWITZ, P. J
• Format: Article
• Language: English
• Subjects: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology; Acetylcholine - pharmacology; Animals; Atropine - pharmacology; Biological and medical sciences; Blood vessels and receptors; Calcitonin Gene-Related Peptide - pharmacology; Dynorphins - pharmacology; Enkephalin, Methionine - pharmacology; Fundamental and applied biological sciences. Psychology; Mesentery - drug effects; Muscle, Smooth, Vascular - drug effects; Naloxone - pharmacology; Nitroarginine - pharmacology; Nociceptin; Nociceptin Receptor; Opioid Peptides - pharmacology; Phentolamine - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Opioid - metabolism; Vascular Resistance - drug effects; Vasodilator Agents - pharmacology; Vertebrates: cardiovascular system
• ISSN: 0167-0115; 1873-1686
• DOI: 10.1016/s0167-0115(98)00117-7

The heptadecapeptide nociceptin, also known as Orphanin FQ, is a recently discovered endogenous ligand for the opioid-like G-protein coupled receptor, ORL1. In the present study, responses to nociceptin were investigated in isolated pressurized resistance arteries from the rat mesenteric vascular bed. Nociceptin in bath concentrations of 10(-9)-10(-6) M induced concentration-dependent increases in arterial diameter when the artery was precontracted with U46619; and administration of the structurally related opioid agonists, dynorphin A and met-enkephalin, had no effect on arterial diameter. Vasodilator responses to nociceptin were not altered by the opioid receptor antagonist naloxone or by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine. Responses to nociceptin were not altered by the muscarinic receptor blocking agent atropine or phentolamine, or the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37). These data suggest that nociceptin has direct vasodilator activity that is not dependent upon the activation of a traditional opioid receptor, muscarinic or CGRP receptors, an inhibitory effect on the adrenergic nervous system, or the release of nitric oxide in isolated resistance arteries from the rat mesentery.