Evidence for transduction of mu but not kappa opioid modulation of extracellular signal-regulated kinase activity by G(z) and G(12) proteins.
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.
Belcheva
M M
MM
Department of Biochemistry & Molecular Biology, St. Louis University School of Medicine, 1402 S. Grand Blvd., St. Louis, MO, USA.
Wong
Y H
YH
Coscia
C J
CJ
D000700:Analgesics / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides; D019556:COS Cells; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D004789:Enzyme Activation; D005227:Fatty Acids / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D037342:Pertussis Toxin; D011759:Pyrrolidines / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013997:Time Factors; D014161:Transduction, Genetic; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000700:Analgesics; D000701:Analgesics, Opioid; D044482:Benzeneacetamides; D005227:Fatty Acids; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D010566:Virulence Factors, Bordetella; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D037342:Pertussis Toxin; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins; C045444:U 69593