ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2011
μ-Opioid receptor coupling to Gα(o) plays an important role in opioid antinociception.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 48 citations in OpenAlex.
- G-protein regulatory network governs receptor internalization dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- G protein regulatory network shapes magnitude and kinetics of behavioral responses in an engineered opioid receptor model.The Journal of biological chemistry · 2026Article
- Mu Opioid Receptor Positive Allosteric Modulator BMS-986122 Confers Agonist-Dependent G Protein Subtype Signaling Bias.Biochemistry · 2025Article
- Can Targeting the Sodium Site via Water Molecules Lead to the Development of Safer Opioids?ACS central science · 2024Article
- GPCR-G protein selectivity revealed by structural pharmacology.The FEBS journal · 2024Review
- Structure-based identification of a G protein-biased allosteric modulator of cannabinoid receptor CB1.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Opioid trail: Tracking contributions to opioid use disorder from host genetics to the gut microbiome.Neuroscience and biobehavioral reviews · 2024Review
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- IUPHAR themed review: Opioid efficacy, bias, and selectivity.Pharmacological research · 2023Review
- Article
- Insights into distinct signaling profiles of the µOR activated by diverse agonists.Nature chemical biology · 2023Article
- Structure-Based Evolution of G Protein-Biased μ-Opioid Receptor Agonists.Angewandte Chemie (International ed. in English) · 2022Article
- Chronic paternal morphine exposure increases sensitivity to morphine-derived pain relief in male progeny.Science advances · 2022Article
- Cellular and circuit diversity determines the impact of endogenous opioids in the descending pain modulatory pathway.Frontiers in systems neuroscience · 2022Review
- Mice Expressing Regulators of G protein Signaling-insensitive Gαo Define Roles ofMolecular pharmacology · 2021Article
- Positive allosteric modulation of the mu-opioid receptor produces analgesia with reduced side effects.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Regulators of G Protein Signaling in Analgesia and Addiction.Molecular pharmacology · 2020Review
- Regulator of G-Protein Signaling (RGS) Protein Modulation of Opioid Receptor Signaling as a Potential Target for Pain Management.Frontiers in molecular neuroscience · 2020Review
- Proteomic and transcriptional profiling of rat amygdala following social play.Behavioural brain research · 2019Article
- Regulators of G-Protein Signaling (RGS) Proteins Promote Receptor Coupling to G-Protein-Coupled Inwardly Rectifying Potassium (GIRK) Channels.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
Opioid analgesics elicit their effects via activation of the mu-opioid receptor (MOR), a G protein-coupled receptor known to interact with Gα(i/o)-type G proteins. Work in vitro has suggested that MOR couples preferentially to the abundant brain Gα(i/o) isoform, Gα(o). However, studies in vivo evaluating morphine-mediated antinociception have not supported these findings. The aim of the present work was to evaluate the contribution of Gα(o) to MOR-dependent signaling by measuring both antinociceptive and biochemical endpoints in a Gα(o) null transgenic mouse strain. Male wild-type and Gα(o) heterozygous null (Gα(o) ⁺/⁻) mice were tested for opioid antinociception in the hot plate test or the warm-water tail withdrawal test as measures of supraspinal or spinal antinociception, respectively. Reduction in Gα(o) levels attenuated the supraspinal antinociception produced by morphine, methadone, and nalbuphine, with the magnitude of suppression dependent on agonist efficacy. This was explained by a reduction in both high-affinity MOR expression and MOR agonist-stimulated G protein activation in whole brain homogenates from Gα(o) ⁺/⁻ and Gα(o) homozygous null (Gα(o)⁻/⁻) mice, compared with wild-type littermates. On the other hand, morphine spinal antinociception was not different between Gα(o) ⁺/⁻ and wild-type mice and high-affinity MOR expression was unchanged in spinal cord tissue. However, the action of the partial agonist nalbuphine was compromised, showing that reduction in Gα(o) protein does decrease spinal antinociception, but suggesting a higher Gα(o) protein reserve. These results provide the first in vivo evidence that Gα(o) contributes to maximally efficient MOR signaling and antinociception.
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