title: Morphine activates opioid receptors without causing their rapid internalization.
abstract: We have examined the endocytic trafficking of epitope-tagged delta and mu opioid receptors expressed in human embryonic kidney (HEK) 293 cells. These receptors are activated by peptide agonists (enkephalins) as well as by the alkaloid agonist drugs etorphine and morphine. Enkephalins and etorphine cause opioid receptors to internalize rapidly (t1/2 approximately 6 min) by a mechanism similar to that utilized by a number of other classes of receptor, as indicated by localization of internalized opioid receptors in transferrin-containing endosomes and inhibition of opioid receptor internalization by hypertonic media. Remarkably, morphine does not stimulate the rapid internalization of either delta or mu opioid receptors, even at high concentrations that strongly inhibit adenylyl cyclase. These data indicate that agonist ligands, which have similar effects on receptor-mediated signaling, can have dramatically different effects on the intracellular trafficking of a G protein-coupled receptor.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, California 90024, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Keith
authors.forename: S R
authors.initials: SR
authors.lastname: Murray
authors.forename: P A
authors.initials: PA
authors.lastname: Zaki
authors.forename: P C
authors.initials: PC
authors.lastname: Chu
authors.forename: D V
authors.initials: DV
authors.lastname: Lissin
authors.forename: L
authors.initials: L
authors.lastname: Kang
authors.forename: C J
authors.initials: CJ
authors.lastname: Evans
authors.forename: M
authors.initials: M
authors.lastname: von Zastrow
mesh_terms: D002460:Cell Line; D004705:Endocytosis / Q000187:drug effects*; D004745:Enkephalins / Q000494:pharmacology; D005048:Etorphine / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006801:Humans; D009020:Morphine / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000819:agonists* / Q000378:metabolism
chemical_list: D004745:Enkephalins; D011957:Receptors, Opioid; D005048:Etorphine; D009020:Morphine