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Abbreviations CaMKII calcium calmodulin kinase CNS central nervous system DAG diacylglycerol DAMGO [d-Ala 2 , N -MePhe 4 ,Gly-ol]enkephalin DOR -opioid receptor ERK1/2 extracellular signal-regulated kinases FRET fluorescence resonance energy transfer GIRK G protein-gated inwardly rectifying potassium channel G6976 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5 H -indolo(2,3- a )pyrrolo(3,4- c )carbazole GPCR G protein-coupled receptor GRK G protein receptor kinase ICI174864 N , N -diallyl-Try 1 .Aib 2,3 ,Leu 5 ]enkephalin JNK c-Jun N-terminal kinases Kir3 GIRK isoform KOR -opioid receptor MAPK mitogen-activated protein kinase ME [Met] 5 enkephalin MOR -opioid receptor NaPP1 4-amino-1- tert -butyl-3-(1-naphthyl)pyrazolo[3,4- d ]pyrimidine NMDA N -methyl-d-aspartate PKC protein kinase C PLD phospholipase D RAVE relative activation versus endocytosis RGS regulator of G protein signaling rMOR a transgenic MOR mouse in which part of the C-terminal region of the DOR is substituted into MOR ROS reactive oxygen species [ 35 S]GTP S 35 S-labeled guanosine-5- O -(3-thio)triphosphate SL327 [ -[amino[(4-aminophenyl)thio]methylene]-2-(trifluoromethyl)benzeneacetonitrile U0126 1,4-diamino-2,3-dicyano-1,4-bis(methylthio)butadiene Authorship Contibutions Wrote or contributed to the writing of the manuscript: Williams, Ingram, Henderson, Chavkin, von Zastrow, Schulz, Koch, Evans, Christie

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