Evidence for transduction of mu but not kappa opioid modulation of extracellular signal-regulated kinase activity by G(z) and G(12) proteins

Cell Signal. 2000 Jul;12(7):481-9. doi: 10.1016/s0898-6568(00)00095-4.


Chronic treatment with micro or kappa opioid agonists (>/=2 h) inhibits EGF-induced ERK activation in opioid receptor overexpressing COS-7 cells. Although acute mu and kappa opioids activate ERK via a pertussis toxin-sensitive G protein, pertussis toxin insensitivity of the chronic mu (but not kappa) action was observed. Here, we tested several pertussis toxin-insensitive G proteins as candidates to transduce acute and/or chronic opioid modulation of ERK. Overexpressed Galpha(z) (but not Galpha(12)) transduced acute mu (but not kappa) ERK activation in pertussis toxin-treated COS-7 cells. Chronic mu (but not kappa) inhibited EGF stimulation of ERK in pertussis toxin-treated cells overexpressing Galpha(z) or Galpha(12). Transfection of Galpha(13) or Galpha(q) blocked inhibition under the same conditions. Overexpressed interfering and non-interfering Galpha(z) mutants differentially affected mu inhibition of ERK consistent with G(z) transduction. In this and prior studies, Galpha(z) and Galpha(12) immunoreactivity were detected in untransfected COS-7 cells, suggesting that these G proteins may be endogenous mediators of chronic mu inhibitory actions on ERK.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesics / pharmacology
  • Analgesics, Opioid / pharmacology
  • Animals
  • Benzeneacetamides*
  • COS Cells
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
  • Enzyme Activation
  • Fatty Acids / metabolism
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Immunoblotting
  • Mitogen-Activated Protein Kinases / metabolism*
  • Mutagenesis, Site-Directed
  • Pertussis Toxin
  • Pyrrolidines / pharmacology
  • Receptors, Opioid, kappa / agonists
  • Receptors, Opioid, kappa / antagonists & inhibitors*
  • Receptors, Opioid, kappa / metabolism*
  • Receptors, Opioid, mu / metabolism
  • Time Factors
  • Transduction, Genetic*
  • Virulence Factors, Bordetella / pharmacology


  • Analgesics
  • Analgesics, Opioid
  • Benzeneacetamides
  • Fatty Acids
  • Pyrrolidines
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Virulence Factors, Bordetella
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Pertussis Toxin
  • Mitogen-Activated Protein Kinases
  • GTP-Binding Proteins
  • U 69593