title: Nociceptin/orphanin FQ activates mitogen-activated protein kinase in Chinese hamster ovary cells expressing opioid receptor-like receptor.
abstract: The effect of nociceptin/orphanin FQ (N/OFQ), an endogenous ligand for the newly identified opioid receptor-like (ORL1) receptor, on mitogen-activated protein kinase (MAPK) was investigated in Chinese hamster ovary cells stably expressing ORL1 receptor. N/OFQ rapidly stimulated phosphorylation and activity of MAPK (p42 and p44 isoforms) in a concentration-dependent manner. The p42 isoform was preferentially activated by N/OFQ. Maximal activation (5.4 +/- 1.2-fold of basal for p42 isoform) was achieved after a 1-min exposure of cells to 100 nM N/OFQ. The activation was blocked completely by pretreatment with pertussis toxin, but was not reversed by naloxone. U-73122, a phospholipase C-specific inhibitor, significantly inhibited phospholipase C activity, as well as MAPK activation stimulated by N/OFQ. Furthermore, N/OFQ-stimulated MAPK activation was suppressed by a protein kinase C-specific inhibitor, chelerythrine. The results demonstrate that N/OFQ can effectively stimulate MAPK by the activation of ORL1 receptor and pertussis toxin-sensitive G proteins, and that phospholipase C, as well as protein kinase C, is critically involved in these processes.
authors.affiliation: Shanghai Institute of Cell Biology, Chinese Academy of Sciences.
authors.forename: L G
authors.initials: LG
authors.lastname: Lou
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Ma
authors.forename: G
authors.initials: G
authors.lastname: Pei
mesh_terms: D000818:Animals; D016466:CHO Cells / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004963:Estrenes / Q000494:pharmacology; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000502:physiology*; D018847:Opioid Peptides / Q000494:pharmacology*; D037342:Pertussis Toxin; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D011957:Receptors, Opioid / Q000819:agonists*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D000097629:Nociceptin
chemical_list: D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004963:Estrenes; D007295:Inositol Phosphates; D009270:Naloxone; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D037342:Pertussis Toxin; D010726:Phosphodiesterase Inhibitors; D011493:Protein Kinase C; D011760:Pyrrolidinones; D011957:Receptors, Opioid; D010738:Type C Phospholipases; D010566:Virulence Factors, Bordetella; D000097629:Nociceptin; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C074854:U 73343