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 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.
Champion
H C
HC
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Pierce
R L
RL
Kadowitz
P J
PJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D004399:Dynorphins / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000494:pharmacology; D008643:Mesentery / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D018847:Opioid Peptides / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000378:metabolism*; D014655:Vascular Resistance / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine; D001285:Atropine; D015740:Calcitonin Gene-Related Peptide; D004399:Dynorphins; D004744:Enkephalin, Methionine; D009270:Naloxone; D019335:Nitroarginine; D018847:Opioid Peptides; D010646:Phentolamine; D011957:Receptors, Opioid; D014665:Vasodilator Agents; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722285:Oprl1 protein, rat