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

Abstract

Chronic treatment with μ or κ opioid agonists (⩾2 h) inhibits EGF-induced ERK activation in opioid receptor overexpressing COS-7 cells. Although acute μ and κ opioids activate ERK via a pertussis toxin-sensitive G protein, pertussis toxin insensitivity of the chronic μ (but not κ) 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 Gα z (but not Gα 12) transduced acute μ (but not κ) ERK activation in pertussis toxin-treated COS-7 cells. Chronic μ (but not κ) inhibited EGF stimulation of ERK in pertussis toxin-treated cells overexpressing Gα z or Gα 12. Transfection of Gα 13 or Gα q blocked inhibition under the same conditions. Overexpressed interfering and non-interfering Gα z mutants differentially affected μ inhibition of ERK consistent with G z transduction. In this and prior studies, Gα z and Gα 12 immunoreactivity were detected in untransfected COS-7 cells, suggesting that these G proteins may be endogenous mediators of chronic μ inhibitory actions on ERK.