Increased abundance of opioid receptor heteromers after chronic morphine administration.
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ABSTRACT:
SUBMITTER: Gupta A
PROVIDER: S-EPMC3125674 | biostudies-literature | 2010 Jul
REPOSITORIES: biostudies-literature
Publications
Increased abundance of opioid receptor heteromers after chronic morphine administration.
Gupta Achla A Mulder Jan J Gomes Ivone I Rozenfeld Raphael R Bushlin Ittai I Ong Edmund E Lim Maribel M Maillet Emeline E Junek Mats M Cahill Catherine M CM Harkany Tibor T Devi Lakshmi A LA
Science signaling 20100720 131
The mu and delta types of opioid receptors form heteromers that exhibit pharmacological and functional properties distinct from those of homomeric receptors. To characterize these complexes in the brain, we generated antibodies that selectively recognize the mu-delta heteromer and blocked its in vitro signaling. With these antibodies, we showed that chronic, but not acute, morphine treatment caused an increase in the abundance of mu-delta heteromers in key areas of the central nervous system tha ...[more]
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Project description:Opioid receptors, including the mu and delta opioid receptors (MOR and DOR) are important targets for the treatment of pain. Although there is mounting evidence that these receptors form heteromers, the functional role of the MOR/DOR heteromer remains unresolved. We have designed and synthesized bivalent ligands as tools to elucidate the functional role of the MOR/DOR heteromer. Our ligands (L2 and L4) are comprised of a compound with low affinity at the DOR tethered to a compound with high affinity at the MOR, with the goal of producing ligands with "tuned affinity" at MOR/DOR heteromers compared to DOR homomers. Here we show that both L2 and L4 demonstrate enhanced affinity at MOR/DOR heteromers compared to DOR homomers, thereby providing unique pharmacological tools to dissect the role of the MOR/DOR heteromer in pain.
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