ArticleThe Journal of clinical investigation2015
Mediation of opioid analgesia by a truncated 6-transmembrane GPCR.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 65 citations in OpenAlex.
- Differential impacts of exon 1-associated and exon 11-associated variants of the rat mu opioid receptor gene, Oprm1, on buprenorphine- and morphine-induced analgesia and respiratory depression in male rats.Molecular pharmacology · 2026Article
- Synthesis and Pharmacology of a Morphinan-Derived Dual Mu-Kappa Opioid Receptor Agonist Analgesic.ACS chemical neuroscience · 2025Article
- Molecular basis of signal transduction mediated by the human GIPR splice variants.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Exploring Pharmacological Functions of Alternatively Spliced Variants of the Mu Opioid Receptor Gene,International journal of molecular sciences · 2022Review
- Disrupting GPCR Complexes with Smart Drug-like Peptides.Pharmaceutics · 2022Review
- Dysregulated expression of the alternatively spliced variant mRNAs of the mu opioid receptor gene, OPRM1, in the medial prefrontal cortex of male human heroin abusers and heroin self-administering male rats.Journal of neuroscience research · 2022Article
- Recent Molecular Insights into Agonist-specific Binding to the Mu-Opioid Receptor.Frontiers in molecular biosciences · 2022Review
- Spoken and Unspoken Matters Regarding the Use of Opioids in Cancer.Journal of pain research · 2022Review
- Alternative Pre-mRNA Splicing of the Mu Opioid Receptor Gene,Biomolecules · 2021Review
- HA-MOP knockin mice express the canonical µ-opioid receptor but lack detectable splice variants.Communications biology · 2021Article
- Alternative Splicing of Opioid Receptor Genes Shows a Conserved Pattern for 6TM Receptor Variants.Cellular and molecular neurobiology · 2021Article
- Interactive Mechanisms of Supraspinal Sites of Opioid Analgesic Action: A Festschrift to Dr. Gavril W. Pasternak.Cellular and molecular neurobiology · 2021Review
- From Pharmacology to Physiology: Endocrine Functions of μ-Opioid Receptor Networks.Trends in endocrinology and metabolism: TEM · 2021Review
- Opioid and neuroHIV Comorbidity - Current and Future Perspectives.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Review
- Synthesis and Pharmacology of a Novel μ-δ Opioid Receptor Heteromer-Selective Agonist Based on the Carfentanyl Template.Journal of medicinal chemistry · 2020Article
- Abuse Liability, Anti-Nociceptive, and Discriminative Stimulus Properties of IBNtxA.ACS pharmacology & translational science · 2020Article
- A Truncated Six Transmembrane Splice Variant MOR-1G Enhances Expression of the Full-Length Seven TransmembraneMolecular pharmacology · 2020Article
- Morphine modulates the expression of mu-opioid receptor exon 5-associated full-length C-terminal splice variants by upregulating miR-378a-3p.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Molecular Basis of Opioid Action: From Structures to New Leads.Biological psychiatry · 2020Review
- Pharmacological Characterization of Levorphanol, a G-Protein Biased Opioid Analgesic.Anesthesia and analgesia · 2019Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The generation of potent opioid analgesics that lack the side effects of traditional opioids may be possible by targeting truncated splice variants of the μ-opioid receptor. μ-Opioids act through GPCRs that are generated from the Oprm1 gene, which undergoes extensive alternative splicing. The most abundant set of Oprm1 variants encode classical full-length 7 transmembrane domain (7TM) μ-opioid receptors that mediate the actions of the traditional μ-opioid drugs morphine and methadone. In contrast, 3-iodobenzoyl-6β-naltrexamide (IBNtxA) is a potent analgesic against thermal, inflammatory, and neuropathic pain that acts independently of 7TM μ-opioid receptors but has no activity in mice lacking a set of 6TM truncated μ-opioid receptor splice variants. Unlike traditional opioids, IBNtxA does not depress respiration or result in physical dependence or reward behavior, suggesting it acts through an alternative μ-opioid receptor target. Here we demonstrated that a truncated 6TM splice variant, mMOR-1G, can rescue IBNtxA analgesia in a μ-opioid receptor-deficient mouse that lacks all Oprm1 splice variants, ablating μ-opioid activity in these animals. Intrathecal administration of lentivirus containing the 6TM variant mMOR-1G restored IBNtxA, but not morphine, analgesia in Oprm1-deficient animals. Together, these results confirm that a truncated 6TM GPCR is both necessary and sufficient for IBNtxA analgesia.
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