Details

Autor(en) / Beteiligte

• Wnendt, Stephan
• Krüger, Thomas
• Janocha, Elke
• Hildebrandt, Dieter
• Englberger, Werner

Titel

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

Ist Teil von

• Molecular pharmacology, 1999-08, Vol.56 (2), p.334-338

Ort / Verlag

United States: American Society for Pharmacology and Experimental Therapeutics

Erscheinungsjahr

1999

Link zum Volltext

Quelle

Electronic Journals Library - Freely accessible e-journals

Beschreibungen/Notizen

• 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 Ψ(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.