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Peripheral Delta Opioid Receptors (DOR) Require Priming for Functional Competence In Vivo
Author(s) -
Rowan Matt P,
Ruparel Nikita B.,
Patwardhan Amol M.,
Berg Kelly A.,
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.726.4
Subject(s) - naltrindole , opioid , chemistry , pharmacology , receptor , hyperalgesia , opioid receptor , agonist , medicine , nociception , biochemistry
Opioid receptors expressed on peripheral sensory neurons in culture are inactive for inhibitory signaling under basal conditions, but become competent to inhibit neuropeptide release and adenylyl cyclase activity after brief pre‐treatment (priming) with bradykinin (BK), arachidonic acid, or direct activators of protein kinase C (PKC). Opioid receptors can also function as oligomers, but in vivo data on priming and oligomers is limited. Here we evaluated whether peripheral DOR require priming in vivo to inhibit PGE2‐induced thermal hyperalgesia in the rat. Results indicate that the BK priming effect was PKC‐dependent, and the antihyperalgesic response to the DOR agonist, DPDPE, was blocked by the antagonist, naltrindole. Administration of the DOR‐kappa opioid receptor (KOR) heterodimer‐selective agonist, 6′GNTI, also produced BK priming‐dependent reversal of thermal hyperalgesia. This study supports in vitro findings that peripheral opioid receptors are inactive under basal conditions and require priming via inflammatory mediators, such as BK, for functional competence in vivo, and suggests a role for peripheral DOR‐KOR hetero‐oligomers in vivo . Supported in part by P01 DA016719 and THCEB/ARP.