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Regulation of delta opioid receptor (DOR) responsiveness in vitro by antagonist occupancy of kappa opioid receptor (KOR)
Author(s) -
Berg Kelly A.,
Sanchez Teresa A.,
Silva Michelle,
Rowan Matt P.,
Hargreaves Kenneth M.,
Clarke William P.
Publication year - 2008
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.22.1_supplement.727.9
Subject(s) - dadle , chemistry , κ opioid receptor , adenylyl cyclase , damgo , opioid , nociceptor , agonist , receptor , pharmacology , μ opioid receptor , neuropeptide , opioid receptor , medicine , endocrinology , nociception , biology , biochemistry
Peripheral opioid administration produces analgesia under conditions of tissue injury or inflammation. DOR, expressed on peripheral sensory neurons in culture, are nonfunctional under basal conditions, however, after brief treatment (priming) with inflammatory mediators such as bradykinin (BK) become competent to inhibit adenylyl cyclase (AC) activity and neuropeptide release. DOR have also been shown to function as oligomers with KOR both in vitro and in vivo . Here we report that occupancy of KOR with a selective antagonist, nor‐BNI (3nM), differentially altered the potency of DOR agonists, DADLE and DPDPE, to inhibit PGE2‐stimulated AC in BK‐primed cultures derived from rat trigeminal ganglion (5–6 days in culture). Concentration curves for DPDPE were shifted to the left 10‐fold whereas curves for DADLE were shifted to the right 20‐fold (DPDPE EC50 was 0.24 nM vs 0.06 nM and for DADLE was 0.058 nM vs 1.19 nM (p <0.05) without or with nor‐BNI). In addition, the DOR‐KOR heterodimer‐selective agonist, 6’GNTI, also produced BK‐priming dependent inhibition of PGE2‐stimulated AC. These data suggest that, in vitro , functional interactions occur between DOR and KOR, possibly as a result of oligomerization, in a ligand‐dependent manner. Moreover, we hypothesize that DOR‐KOR interactions may regulate nociceptor function and participate in opioid‐mediated analgesia in inflamed tissue. Supported by a DA 016719.