Nociceptin, an endogenous ligand for the ORL1 receptor, has novel hypotensive activity 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 intravenous administration of nociceptin were investigated in the systemic vascular bed of the rat. Nociceptin induced dose-related decreases in systemic arterial pressure when injected in doses of 1-30 nmol/kg i.v. In terms of relative vasodepressor activity, nociceptin was approximately 10-fold more potent than the nitric oxide donor, DEA/NO, and 10-fold less potent than adrenomedullin. The duration of the vasodepressor response to nociceptin was shorter than adrenomedullin but longer than DEA/NO. These results show that nociceptin has significant vasodepressor activity in the rat.
Champion
H C
HC
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Kadowitz
P J
PJ
D053607:Adrenomedullin; D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006834:Hydrazines / Q000494:pharmacology; D007022:Hypotension / Q000139:chemically induced; D008024:Ligands; D008297:Male; D008969:Molecular Sequence Data; D009589:Nitrogen Oxides; D018847:Opioid Peptides / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D053607:Adrenomedullin; D006834:Hydrazines; D008024:Ligands; D009589:Nitrogen Oxides; D018847:Opioid Peptides; D010455:Peptides; D011957:Receptors, Opioid; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; C000722285:Oprl1 protein, rat