Molecular basis of differences in ()(trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidiny)-cyclohexyl]benzeneacetamide-induced desensitization and phosphorylation between human and rat -opioid receptors expressed in Chinese hamster ovary cells. Mol Pharmacol

The agonist ()(trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrro-lidiny)-cyclohexyl]benzeneacetamide [()U50,488H] caused desensitization of the human -opioid receptor (hkor) and Flag-tagged hkor (Flag-hkor) but not the rat -opioid receptor (rkor) and Flag-tagged rkor (Flag-rkor) stably expressed in CHO cells as assessed by guanosine 5-O-(3-[35S]thiotriphosphate) bind-ing. In addition, ()U50,488H stimulation enhanced phosphor-ylation of the Flag-hkor, but not Flag-rkor. ()U50,488H-in-duced phosphorylation of the Flag-hkor was reduced by expression of the dominant negative mutant GRK2-K220R, demonstrating the involvement of G protein-coupled receptor kinases (GRKs). However, expression of GRK2 and arrestin-2 or GRK3 and arrestin-3 did not result in desensitization or phosphorylation of the Flag-rkor after ()U50,488H pretreat