ArticleMolecular pain2010
A novel alternatively spliced isoform of the mu-opioid receptor: functional antagonism.
Article in Molecular pain, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Japanese GWAS identifies variants for bust-size, dysmenorrhea, and menstrual fever that are eQTLs for relevant protein-coding or long non-coding RNAs.Scientific reports · 2018Pooled it
- Morphine-inducedFrontiers in neuroscience · 2026Article
- Opioid-Induced Hyperalgesia and Tolerance Are Driven by HCN Ion Channels.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Constitutive signal bias mediated by the human GHRHR splice variant 1.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Identification and characterization of novel candidate compounds targeting 6- and 7-transmembrane μ-opioid receptor isoforms.British journal of pharmacology · 2021Article
- Alternative Splicing of Opioid Receptor Genes Shows a Conserved Pattern for 6TM Receptor Variants.Cellular and molecular neurobiology · 2021Article
- Opioid and neuroHIV Comorbidity - Current and Future Perspectives.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Review
- A Truncated Six Transmembrane Splice Variant MOR-1G Enhances Expression of the Full-Length Seven TransmembraneMolecular pharmacology · 2020Article
- Article
- Stabilization of μ-opioid receptor facilitates its cellular translocation and signaling.Proteins · 2019Article
- Alternative Splicing of the Delta-Opioid Receptor Gene Suggests Existence of New Functional Isoforms.Molecular neurobiology · 2019Article
- Mechanistic assessment of the analgesic, anti-inflammatory and antipyretic actions of Dalbergia saxatilis in animal models.Pharmaceutical biology · 2017Article
- Morphine-induced hyperalgesia involves mu opioid receptors and the metabolite morphine-3-glucuronide.Scientific reports · 2017Article
- Genetic dissociation of morphine analgesia from hyperalgesia in mice.Psychopharmacology · 2017Article
- β-Adrenergic receptor gene expression in HIV-associated neurocognitive impairment and encephalitis: implications for MOR-1K subcellular localization.Journal of neurovirology · 2016Article
- Regulation and Functional Implications of Opioid Receptor Splicing in Opioid Pharmacology and HIV Pathogenesis.Journal of cellular physiology · 2016Review
- Structural and functional interactions between six-transmembrane μ-opioid receptors and β2-adrenoreceptors modulate opioid signaling.Scientific reports · 2015Article
- μ-Opioid receptor 6-transmembrane isoform: A potential therapeutic target for new effective opioids.Progress in neuro-psychopharmacology & biological psychiatry · 2015Review
- Alternative Splicing of G Protein-Coupled Receptors: Relevance to Pain Management.Mayo Clinic proceedings · 2015Review
- Differential Regulation of 6- and 7-Transmembrane Helix Variants of μ-Opioid Receptor in Response to Morphine Stimulation.PloS one · 2015Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundOpioids are the most widely used analgesics for the treatment of clinical pain. They produce their therapeutic effects by binding to mu-opioid receptors (MORs), which are 7 transmembrane domain (7TM) G-protein-coupled receptors (GPCRs), and inhibiting cellular activity. However, the analgesic efficacy of opioids is compromised by side-effects such as analgesic tolerance, dependence and opioid-induced hyperalgesia (OIH). In contrast to opioid analgesia these side effects are associated with cellular excitation. Several hypotheses have been advanced to explain these phenomena, yet the molecular mechanisms underlying tolerance and OIH remain poorly understood.
resultsWe recently discovered a new human alternatively spliced isoform of MOR (MOR1K) that is missing the N-terminal extracellular and first transmembrane domains, resulting in a 6TM GPCR variant. To characterize the pattern of cellular transduction pathways activated by this human MOR1K isoform, we conducted a series of pharmacological and molecular experiments. Results show that stimulation of MOR1K with morphine leads to excitatory cellular effects. In contrast to stimulation of MOR1, stimulation of MOR1K leads to increased Ca2+ levels as well as increased nitric oxide (NO) release. Immunoprecipitation experiments further reveal that unlike MOR1, which couples to the inhibitory Galphai/o complex, MOR1K couples to the stimulatory Galphas complex.
conclusionThe major MOR1 and the alternative MOR1K isoforms mediate opposite cellular effects in response to morphine, with MOR1K driving excitatory processes. These findings warrant further investigations that examine animal and human MORK1 expression and function following chronic exposure to opioids, which may identify MOR1K as a novel target for the development of new clinically effective classes of opioids that have high analgesic efficacy with diminished ability to produce tolerance, OIH, and other unwanted side-effects.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.