Role of extracellular signal-regulated kinases in opioid-induced adenylyl cyclase superactivation in human embryonic kidney 293 cells.
The mu-opioid receptor stimulates the activity of extracellular signal-regulated protein kinase 1/2 (ERK1/2) in recombinant human embryonic kidney (HEK) 293 cells but this stimulatory response is abolished by prolonged opioid treatment. Chronic opioid treatment of the same cells has also been shown to induce adenylyl cyclase (AC) superactivation. This study examined the role of ERK1/2 activity in opioid-induced AC superactivation. Acute opioid treatment of HEK 293 cells expressing mu-opioid receptors resulted in the activation of ERK1/2, and this response was abolished in the presence of U0126, a MEK1/2 inhibitor. Despite a complete blockade of ERK1/2 phosphorylation, U0126 did not affect opioid-induced AC superactivation, indicating that ERK1/2 activity was not required for opioid-induced AC superactivation in HEK 293 cells.
Tso
P H
PH
Department of Biochemistry, the Molecular Neuroscience Center and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Wong
Y H
YH
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004622:Embryo, Mammalian; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000201:enzymology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D000242:Cyclic AMP; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D000262:Adenylyl Cyclases