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REVIEW : ORL-1: An Awkward Child of the Opioid Receptor Family

Department of Psychiatry and Biobehavioral Sciences University of California, Los Angeles Los Angeles, California

Chris J. Evans

Department of Psychiatry and Biobehavioral Sciences University of California, Los Angeles Los Angeles, California

The cloning of the -opioid receptor allowed for the rapid cloning of the two other classically defined opioid receptors, the µ- and -opioid receptors. However, several groups cloned a fourth receptor (ORL-1, for opioid receptor-like) that had high homology to the opioid receptors but did not bind any known endogenous opioid peptides (i.e., endorphins) or exogenous opiates. Recently, two independent groups isolated a 17- amino-acid peptide that is an endogenous ligand for ORL-1; one group named it orphanin FQ (OFQ), the other named it nociceptin (N). It was reported that intracerebroventricular administration of this heptadeca peptide (OFQ/N) in mice induced an increased responsiveness to painful stimuli, an effect in striking contrast to the analgesia that is a hallmark of classical opiate drugs. Further research has revealed that OFQ/N has complex effects on pain perception: OFQ/N has been touted as having analgesic, hyperalgesic, and anti opioid properties. In addition to discussing these disparate findings, this review highlights the structural and pharmacological parallels between ORL-1 and opioid receptors as well as their respective endogenous ligands. NEUROSCIENTIST 4:172-184, 1998

Key Words: ORL-1 • Orphanin FQ • Opioid receptor • Orphan • Nociceptin • Dynorphin • Nociception • Antiopioid

The Neuroscientist, Vol. 4, No. 3, 172-184 (1998)
DOI: 10.1177/107385849800400313


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