Agonistic Effect of Buprenorphine in a Nociceptin/OFQ Receptor-Triggered Reporter Gene Assay

Abstract

The role of the opioid-like receptor 1 (ORL1) and its endogenous ligand, nociceptin/orphanin FQ (N/OFQ), in nociception, anxiety, and learning remains to be defined. To allow the rapid identification of agonists and antagonists, a reporter gene assay has been established in which the ORL1 receptor is functionally linked to the cyclic AMP-dependent expression of luciferase. N/OFQ and N/OFQ_1-13NH₂ inhibited the forskolin-induced luciferase gene expression with IC₅₀ values of 0.81 ± 0.5 and 0.87 ± 0.16 nM, respectively. Buprenorphine was identified as a full agonist at the ORL1 receptor with an IC₅₀ value of 8.4 ± 2.8 nM. Fentanyl and 7-benzylidenenaltrexone displayed a weak agonistic activity. The ORL1 antagonist [Phe¹Ψ(CH₂-NH)Gly²]N/OFQ_(1–13)NH₂clearly behaved as an agonist in this assay with an IC₅₀value of 85 ± 47 nM. Thus, there is still a need for antagonistic tool compounds that might help to elucidate the neurophysiological role of N/OFQ.