Extracellular signal-regulated kinase/mitogen-activated protein kinases block internalization of deltaopioid receptors

Translocation of G protein-coupled receptors (GPCRs) from the cell membrane to cytosol depends on the kind of ligand acti-vating the receptor. This principle is clearly demonstrated for opioid receptors, because diverse opiate agonists rapidly in-duce receptor internalization, whereas morphine almost fails. We report here the impact of mitogen-activated protein (MAP) kinase isoforms extracellular signal-regulated kinase (ERK)1/2 on the internalization of -opioid receptors (DORs) expressed in human embryonic kidney (HEK)293 cells. Receptor activation by etorphine turned out to transiently phosphorylate ERK/MAP kinases and bring about DOR internalization within 20 min. In contrast, prolonged exposure of HEK293 cells to morphine excited persistent phosphorylation of ERK/MAP kinases, and those cells failed to internalize the opioid receptor. When ERK