title: Pertussis toxin-insensitive signaling of the ORL1 receptor: coupling to Gz and G16 proteins.
abstract: Nociceptin/OFQ is the endogenous ligand for the G protein-coupled opioid receptor-like (ORL1) receptor. To elucidate the cellular functions of the ORL1 receptor, we examined its ability to interact with Gz and G16, two pertussis toxin (PTX)-insensitive G proteins that are known molecular partners for the opioid receptors. In HEK 293 cells transiently expressing the ORL1 and dopamine D1 receptors, nociceptin/OFQ dose-dependently inhibited dopamine-stimulated cyclic AMP (cAMP) accumulation in a PTX-sensitive manner. However, PTX failed to block the nociceptin/OFQ-induced inhibition of dopamine-stimulated cAMP accumulation in HEK 293 cells co-expressing the alpha-subunit of Gz. This result indicates functional interaction between the ORL1 receptor and Gz. A similar result was obtained with retinoic acid-differentiated SH-SY5Y cells, which endogenously express both the ORL1 receptor and Gz. When the ORL1 receptor was transiently co-expressed in COS-7 cells with the alpha-subunit of G16, nociceptin/OFQ dose-dependently stimulated the formation of inositol phosphates. Nociceptin-induced stimulation of phospholipase C was absolutely dependent on the co-expression of alpha16 and exhibited the appropriate ligand selectivity. In terms of its ability to interact with PTX-insensitive G proteins, the ORL1 receptor behaves very much like the opioid receptors.
authors.affiliation: Department of Biology and Biotechnology Research Institute, Hong Kong University of Science and Technology, Kowloon, China.
authors.forename: J S
authors.initials: JS
authors.lastname: Chan
authors.forename: L Y
authors.initials: LY
authors.lastname: Yung
authors.forename: J W
authors.initials: JW
authors.lastname: Lee
authors.forename: Y L
authors.initials: YL
authors.lastname: Wu
authors.forename: G
authors.initials: G
authors.lastname: Pei
authors.forename: Y H
authors.initials: YH
authors.lastname: Wong
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D002460:Cell Line; D004351:Drug Resistance; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D018847:Opioid Peptides / Q000494:pharmacology; D037342:Pertussis Toxin; D011957:Receptors, Opioid / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D010738:Type C Phospholipases / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D019204:GTP-Binding Proteins; D018847:Opioid Peptides; D037342:Pertussis Toxin; D011957:Receptors, Opioid; D010738:Type C Phospholipases; D010566:Virulence Factors, Bordetella; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722283:OPRL1 protein, human