Agonistic effect of buprenorphine in a nociceptin/OFQ receptor-triggered reporter gene assay.
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(1-13)NH(2) inhibited the forskolin-induced luciferase gene expression with IC(50) 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 IC(50) value of 8.4 +/- 2.8 nM. Fentanyl and 7-benzylidenenaltrexone displayed a weak agonistic activity. The ORL1 antagonist [Phe(1)Psi(CH(2)-NH)Gly(2)]N/OFQ((1-13))NH(2) clearly behaved as an agonist in this assay with an IC(50) value 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.
Department of Molecular Pharmacology, Grünenthal GmbH, Aachen, Germany. wnendt@post.rwth-aachen.de
S
S
Wnendt
T
T
Krüger
E
E
Janocha
D
D
Hildebrandt
W
W
Englberger
D000818:Animals; D001709:Biotechnology / Q000379:methods; D002047:Buprenorphine / Q000494:pharmacology*; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D017930:Genes, Reporter; D006801:Humans; D008024:Ligands; D008156:Luciferases / Q000235:genetics; D009294:Narcotics / Q000032:analysis / Q000494:pharmacology*; D018847:Opioid Peptides / Q000737:chemistry / Q000378:metabolism; D011957:Receptors, Opioid / Q000819:agonists* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D002047:Buprenorphine; D008024:Ligands; D008156:Luciferases; D009294:Narcotics; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin