Nociceptin/orphanin FQ activates mitogen-activated protein kinase in Chinese hamster ovary cells expressing opioid receptor-like receptor

J Neurochem. 1998 Mar;70(3):1316-22. doi: 10.1046/j.1471-4159.1998.70031316.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells / chemistry
  • CHO Cells / drug effects
  • CHO Cells / enzymology
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cricetinae
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Estrenes / pharmacology
  • Humans
  • Inositol Phosphates / metabolism
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Nociceptors / physiology*
  • Opioid Peptides / pharmacology*
  • Pertussis Toxin
  • Phosphodiesterase Inhibitors / pharmacology
  • Protein Kinase C / metabolism
  • Pyrrolidinones / pharmacology
  • Receptors, Opioid / agonists*
  • Type C Phospholipases / antagonists & inhibitors
  • Type C Phospholipases / metabolism
  • Virulence Factors, Bordetella / pharmacology


  • Estrenes
  • Inositol Phosphates
  • Narcotic Antagonists
  • Opioid Peptides
  • Phosphodiesterase Inhibitors
  • Pyrrolidinones
  • Receptors, Opioid
  • Virulence Factors, Bordetella
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • U 73343
  • Naloxone
  • nociceptin
  • Pertussis Toxin
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Type C Phospholipases