ArticleDrug and alcohol dependence2009
Morphine-induced physiological and behavioral responses in mice lacking G protein-coupled receptor kinase 6.
Article in Drug and alcohol dependence, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- In vitro and in vivo pharmacological characterization of fentanyl analogs.Neuropharmacology · 2025Article
- Oxycodone withdrawal induces HDAC1/HDAC2-dependent transcriptional maladaptations in the reward pathway in a mouse model of peripheral nerve injury.Nature neuroscience · 2023Article
- Influence of G protein-biased agonists of μ-opioid receptor on addiction-related behaviors.Pharmacological reports : PR · 2021Review
- Buprenorphine: Far Beyond the "Ceiling".Biomolecules · 2021Review
- Review
- Dissecting the roles of GRK2 and GRK3 in μ-opioid receptor internalization and β-arrestin2 recruitment using CRISPR/Cas9-edited HEK293 cells.Scientific reports · 2020Article
- Toward Directing Opioid Receptor Signaling to Refine Opioid Therapeutics.Biological psychiatry · 2020Review
- G-Protein-Coupled Receptors Are Dynamic Regulators of Digestion and Targets for Digestive Diseases.Gastroenterology · 2019Review
- Phosphorylation-deficient G-protein-biased μ-opioid receptors improve analgesia and diminish tolerance but worsen opioid side effects.Nature communications · 2019Article
- GRK6 regulates ROS response and maintains hematopoietic stem cell self-renewal.Cell death & disease · 2016Article
- G protein-coupled receptor kinases as regulators of dopamine receptor functions.Pharmacological research · 2016Review
- Toll-like receptor 4 contributes to the inhibitory effect of morphine on colonic motility in vitro and in vivo.Scientific reports · 2015Article
- Disruption of dopamine D1 receptor phosphorylation at serine 421 attenuates cocaine-induced behaviors in mice.Neuroscience bulletin · 2014Article
- Loss of morphine reward and dependence in mice lacking G protein-coupled receptor kinase 5.Biological psychiatry · 2014Article
- Biological redundancy of endogenous GPCR ligands in the gut and the potential for endogenous functional selectivity.Frontiers in pharmacology · 2014Review
- Development of functionally selective, small molecule agonists at kappa opioid receptors.The Journal of biological chemistry · 2013Article
- Opioid receptor interacting proteins and the control of opioid signaling.Current pharmaceutical design · 2013Review
- GIRK channel modulation by assembly with allosterically regulated RGS proteins.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Elimination of GRK2 from cholinergic neurons reduces behavioral sensitivity to muscarinic receptor activation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Distinct cellular and subcellular distributions of G protein-coupled receptor kinase and arrestin isoforms in the striatum.PloS one · 2012Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
G protein-coupled receptor kinases (GRKs) are a family of intracellular proteins that desensitize and regulate the responsiveness of G protein-coupled receptors (GPCRs). In the present study, we assessed the contribution of GRK6 to the regulation and responsiveness of the G protein-coupled mu-opioid receptor (microOR) in response to morphine in vitro and in vivo using mice lacking GRK6. In cell culture, overexpression of GRK6 facilitates morphine-induced beta-arrestin2 (betaarrestin2) recruitment and receptor internalization, suggesting that this kinase may play a role in regulating the microOR. In vivo, we find that acute morphine treatment induces greater locomotor activation but less constipation in GRK6 knockout (GRK6-KO) mice compared to their wild-type (WT) littermates. The GRK6-KO mice also appear to be "presensitized" to the locomotor stimulating effects induced by chronic morphine treatment, yet these animals do not display more conditioned place preference than WT mice do. Furthermore, several other morphine-mediated responses which were evaluated, including thermal antinociception, analgesic tolerance, and physical dependence, were not affected by ablation of the GRK6 gene. Collectively, these results suggest that GRK6 may play a role in regulating some, but not all morphine-mediated responses. In addition, these findings underscore that the contribution of a particular regulatory factor to receptor function can differ based upon the specific cell composition and physiology assessed, and illustrate the need for using caution when interpreting the importance of interactions observed in cell culture.
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Registered trials
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.