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Agonist‐specific resensitization of the delta opioid receptor
Author(s) -
Feschenko Marina S,
Dave Kuldip D.,
Windh Rolf T.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a251
Subject(s) - agonist , mapk/erk pathway , naltrindole , chemistry , δ opioid receptor , receptor , chinese hamster ovary cell , microbiology and biotechnology , endocrinology , pharmacology , medicine , biology , kinase , opioid receptor , biochemistry
We used a structurally diverse set of DOR agonists to address the role of delta opioid receptor (DOR) trafficking in desensitization and resensitization. All tested DOR agonists activated extracellular signal‐regulated kinase (ERK) within 5 min and induced translocation of DOR to the perinuclear area within 60 min in CHO cells expressing myc‐tagged human DOR. Whereas DOR‐mediated ERK activity was abolished after preincubation with any agonist for more than 1 h, significant agonist‐specific differences were found in the ability of DOR to return to the surface and to resensitize after agonist washout and recovery. DOR failed to return to the plasma membrane, and ERK sensitivity was not restored, within 25 h recovery after treatment with BW373U86, SNC80 and ARM2263. In contrast, both surface DOR and ERK sensitivity returned in a time‐dependent manner after treatment with DPDPE, deltorphin II, and SB227122. Brefeldin A, an inhibitor of export from endoplasmic reticulum, blocked both processes, suggesting that return of DOR to the plasma membrane is required for recovery of DOR‐mediated ERK activation. DOR was not degraded after treatment with any agonist: no loss of total DOR immunoreactivity, and no colocalization with the lysosomal marker LAMP2, was detected in CHO cells after overnight incubation. Furthermore, the DOR antagonist naltrindole, when added during recovery, greatly enhanced return of DOR to the cell surface after treatment with BW373U86‐like, but not DPDPE‐like, agonists. These data demonstrate agonist‐specific rates of DOR resensitization and suggest that differential resensitization depends on the nature of the agonist‐receptor complex rather than differential targeting.