RGD Reference Report - Heterodimerization of opioid receptor-like 1 and mu-opioid receptors impairs the potency of micro receptor agonist. - Rat Genome Database

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Heterodimerization of opioid receptor-like 1 and mu-opioid receptors impairs the potency of micro receptor agonist.

Authors: Wang, HL  Hsu, CY  Huang, PC  Kuo, YL  Li, AH  Yeh, TH  Tso, AS  Chen, YL 
Citation: Wang HL, etal., J Neurochem. 2005 Mar;92(6):1285-94.
RGD ID: 9835006
Pubmed: PMID:15748148   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1471-4159.2004.02921.x   (Journal Full-text)

Nociceptin activation of ORL1 (opioid receptor-like 1 receptor) has been shown to antagonize mu receptor-mediated analgesia at the supraspinal level. ORL1 and mu-opioid receptor (muR) are co-expressed in several subpopulations of CNS neurons involved in regulating pain transmission. The amino acid sequence of ORL1 also shares a high degree of homology with that of mu receptor. Thus, it is hypothesized that ORL1 and muR interact to form the heterodimer and that ORL1/muR heterodimerization may be one molecular basis for ORL1-mediated antiopioid effects in the brain. To test this hypothesis, myc-tagged ORL1 and HA-tagged muR are co-expressed in human embryonic kidney (HEK) 293 cells. Co-immunoprecipitation experiments demonstrate that ORL1 dimerizes with muR and that intracellular C-terminal tails of ORL1 and muR are required for the formation of ORL1/muR heterodimer. Second messenger assays further indicate that formation of ORL1/muR heterodimer selectively induces cross-desensitization of muR and impairs the potency by which [D-Ala(2),N-methyl-Phe(4),Gly-ol(5)]enkephalin (DAMGO) inhibits adenylate cyclase and stimulates p42/p44 mitogen-activated protein kinase (MAPK) phosphorylation. These results provide the evidence that ORL1/muR heterodimerization and the resulting impairment of mu receptor-activated signaling pathways may contribute to ORL1-mediated antiopioid effects in the brain.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway  IDA 9835006; 9835006 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding  IPIOprm1 (Rattus norvegicus)9835006protein C-terminus bindingRGD 
protein binding  IPIOprl1 (Rattus norvegicus)9835006protein C-terminus bindingRGD 

Objects Annotated

Genes (Rattus norvegicus)
Oprl1  (opioid related nociceptin receptor 1)
Oprm1  (opioid receptor, mu 1)


Additional Information