ArticleProceedings of the National Academy of Sciences of the United States of America2009
Functional characterization of human variants of the mu-opioid receptor gene.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 71 citations in OpenAlex.
- Narrative review of the scientific and methodological explanations for 101 mechanisms of opioid tolerance.Pain reports · 2025Article
- Intracellular Pocket Conformations Determine Signaling Efficacy through the μ Opioid Receptor.Journal of chemical information and modeling · 2025Article
- Intracellular pocket conformations determine signaling efficacy through thebioRxiv : the preprint server for biology · 2024Article
- Cell-type specific molecular architecture for mu opioid receptor function in pain and addiction circuits.Neuropharmacology · 2023Review
- Article
- Modulation of OPRM1 Alternative Splicing by Morphine and HIV-1 Nef.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2022Article
- Functional expression of opioid receptors and other human GPCRs in yeast engineered to produce human sterols.Nature communications · 2022Article
- Novel variants of engineered water soluble mu opioid receptors with extensive mutations and removal of cysteines.Proteins · 2021Article
- Early Life Stress and Risks for Opioid Misuse: Review of Data Supporting Neurobiological Underpinnings.Journal of personalized medicine · 2021Review
- The G protein-first activation mechanism of opioid receptors by Gi protein and agonists.QRB discovery · 2021Article
- Review
- Molecular Basis of Opioid Action: From Structures to New Leads.Biological psychiatry · 2020Review
- Candidate gene analyses for acute pain and morphine analgesia after pediatric day surgery: African American versus European Caucasian ancestry and dose prediction limits.The pharmacogenomics journal · 2019Article
- Synthesis and pharmacological characterization of ethylenediamine synthetic opioids in human μ-opiate receptor 1 (OPRM1) expressing cells.Pharmacology research & perspectives · 2019Article
- Structure of the µ-opioid receptor-GNature · 2018Article
- A multicenter study of attitudinal barriers to cancer pain management.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2017Article
- Association of morphine-induced analgesic tolerance with changes in gene expression ofIranian journal of basic medical sciences · 2016Article
- The AC/AG Diplotype for the 118A>G and IVS2 + 691G>C Polymorphisms of OPRM1 Gene is Associated with Sleep Quality Among Opioid-Dependent Patients on Methadone Maintenance Therapy.Pain and therapy · 2016Article
- Reverse of Acute and Chronic Morphine Tolerance by Lithocholic AcidFrontiers in pharmacology · 2016Article
- The Opposing Roles of IVS2+691 CC Genotype and AC/AG Diplotype of 118A>G and IVS2+691G>C of OPRM1 Polymorphisms in Cold Pain Tolerance Among Opioid-Dependent Malay Males on Methadone Therapy.Pain and therapy · 2015Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Opioids and their receptors have an important role in analgesia and alcohol and substance use disorders (ASUD). We have identified several naturally occurring amino acid changing variants of the human mu-opioid receptor (MOR), and assessed the functional consequences of these previously undescribed variants in stably expressing cell lines. Several of these variants had altered trafficking and signaling properties. We found that an L85I variant showed significant internalization in response to morphine, in contrast to the WT MOR, which did not internalize in response to morphine. Also, when L85I and WT receptor were coexpressed, WT MOR internalized with the L85I MOR, suggesting that, in the heterozygous condition, the L85I phenotype would be dominant. This finding is potentially important, because receptor internalization has been associated with development of tolerance to opiate analgesics. In contrast, an R181C variant abolished both signaling and internalization in response to saturating doses of the hydrolysis-resistant enkephalin [D-Ala2,N-MePhe4,Gly5-ol]enkephalin (DAMGO). Coexpression of the R181C and WT receptor led to independent trafficking of the 2 receptors. S42T and C192F variants showed a rightward shift in potency of both morphine and DAMGO, whereas the S147C variant displayed a subtle leftward shift in morphine potency. These data suggest that these and other such variants may have clinical relevance to opioid responsiveness to both endogenous ligands and exogenous drugs, and could influence a broad range of phenotypes, including ASUD, pain responses, and the development of tolerance to morphine.
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