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-reg ulated protein kinase 1/2 (ERK1/2) in recombinant human embryonic kidney (H EK) 293 cells but this stimulatory response is abolished by prolonged opioi d treatment. Chronic opioid treatment of the same cells has also been shown to induce adenylyl cyclase (AC) superactivation. This study examined the r ole of ERK1/2 activity in opioid-induced AC superactivation. Acute opioid t reatment of HEK 293 cells expressing mu -opioid receptors resulted in the a ctivation of ERK1/2, and this response was abolished in the presence of U01 26, a MEK1/2 inhibitor. Despite a complete blockade of ERK1/2 phosphorylati on, 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. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.