Molecular characterization and functional expression of opioid receptor—like1 receptor

摘要

The opioid receptor-like1 receptor(ORL1),an orphan receptor whose human and murine complementary DNAs,has been characterized recently.ORL1 transcripts are particularly abundant in the central nervous system.We demonstrated that ORL1 expressed in human neuroblastoma SK-N-SH and SH-SY5Y cell lines by radioligand binding assay,reverse transcription polymerase chain reaction (RT-PCR) and Northern analysis in the present study.Stimulation with ORL1 specific agonist,nociceptin/orphanin FQ,increased [35S]GTPγS binding to SK-N-SH cell membranes (EC50=14±0.45 nM),and attenuated forskolin-stimulated accumulation of cellular cAMP(EC50=0.80±0.45 nM),indicative that activation of ORL1 activates G proteins and inhibits adenylyl cyclase.Activation of ORL1 receptor was also accessed using CHO:hORL1 cell line by microphysiometer.Treatment of nociceptin/orphanin FQ increased extracellular acidification rate significantly.