The stimulatory effect of opioids on mitogen-activated protein kinase in Chinese hamster ovary cells transfected to express mu-opioid receptors.

The mitogen-activated protein (MAP) kinase of Chinese hamster ovary cells (CHO mu66 cell line) transfected to express mu-opioid receptors was markedly activated by mu agonists. The rank order of effectiveness of agonists was approximately the same as the rank order of their binding affinities to the mu receptor. The delta and kappa receptor-specific agonists cyclic[D-Pen2, D-Pen5]enkephalin and U69,593 showed a very weak stimulatory effect. The mu agonist-stimulated MAP kinase activity peaked at approximately 4-8 min and lasted almost 1 hr. The stimulatory effect of mu agonists was antagonized by the opioid receptor antagonist naltrexone and inhibited by pretreatment of cells with pertussis toxin. This opioid-induced activation of MAP kinase activity may have a role in the long term effects of opioids.