μ-Opioid receptor desensitization by β-arrestin-2 determines morphine tolerance but not dependence
@article{Bohn2000OpioidRD, title={$\mu$-Opioid receptor desensitization by $\beta$-arrestin-2 determines morphine tolerance but not dependence}, author={Laura M. Bohn and Raul R. Gainetdinov and Fang-Tsyr Lin and Robert J. Lefkowitz and Marc G. Caron}, journal={Nature}, year={2000}, volume={408}, pages={720-723} }
Morphine is a powerful pain reliever, but also a potent inducer of tolerance and dependence. The development of opiate tolerance occurs on continued use of the drug such that the amount of drug required to elicit pain relief must be increased to compensate for diminished responsiveness. In many systems, decreased responsiveness to agonists has been correlated with the desensitization of G-protein-coupled receptors. In vitro evidence indicates that this process involves phosphorylation of G…
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Cellular Morphine Tolerance Produced by βArrestin-2-Dependent Impairment of μ-Opioid Receptor Resensitization
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- 2011
Surprisingly, recovery of MOR from acute desensitization in LC neurons does not require βarr-2- or dynamin-dependent trafficking, and chronic morphine treatment modifies GRK2–βarrestin-2–dynamin- dependent MOR trafficking to impair receptor resensituation, thereby contributing to opioid tolerance inLC neurons by reducing the number of functional receptors on the surface membrane.
A G protein signaling-biased agonist at the μ-opioid receptor reverses morphine tolerance while preventing morphine withdrawal
- Biology, PsychologyNeuropsychopharmacology
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Interestingly, substitution with SR-17018 in morphine-tolerant mice restores morphine potency and efficacy, whereas the onset of opioid withdrawal is prevented, in contrast to buprenorphine, which can suppress withdrawal, but produces and maintains morphine antinociceptive tolerance.
μ-Opioid Receptors Desensitize Less Rapidly than δ-Opioid Receptors Due to Less Efficient Activation of Arrestin*
- Biology, ChemistryThe Journal of Biological Chemistry
- 2002
The results suggest that DOR desensitization involves phosphorylation of both the carboxyl-terminal tail and the second intracellular loop that together leads to a more efficient activation of arrestin and thus faster desensItization.
Analgesic tone conferred by constitutively active mu opioid receptors in mice lacking β-arrestin 2
- BiologyMolecular pain
- 2011
It is demonstrated that the induction of constitutive μ receptor activity in vivo in β-arr2-/- mice prolongs tail withdrawal from noxious heat, a phenomenon that was reversed by inverse agonists, but not by antagonists that lack negative efficacy.
Tolerance to Repeated Morphine Administration Is Associated with Increased Potency of Opioid Agonists
- BiologyNeuropsychopharmacology
- 2008
The present data indicate that antinociceptive tolerance may be triggered by enhanced agonist potency resulting in increased desensitization of μ-opioid receptors.
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- BiologyNature Communications
- 2019
These findings identify carboxyl-terminal multisite phosphorylation as key step that drives acute μ-opioid receptor desensitization and long-term tolerance and predict that G-protein-biased µ-agonists are still likely to elicit severe adverse effects.
The role of beta-arrestin2 in the severity of antinociceptive tolerance and physical dependence induced by different opioid pain therapeutics
- BiologyNeuropharmacology
- 2011
The role of opioid receptor internalization and beta-arrestins in the development of opioid tolerance.
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- 2005
Modification of opioid receptor internalization by affecting the interaction between opioid receptors and beta-arrestins may be a therapeutic target for reducing opioid tolerance.
Complex formation between the vasopressin 1b receptor, β-arrestin-2, and the μ-opioid receptor underlies morphine tolerance
- BiologyNature Neuroscience
- 2018
It is shown that morphine tolerance was delayed in mice lacking vasopressin 1b receptors (V1bRs) or after administration of V1bR antagonist into the rostral ventromedial medulla, where transcripts for V 1bRs and μ-opioid receptors are co-localized.
Morphine-Induced μ-Opioid Receptor Desensitization
- Biology, PsychologyMolecular Pharmacology
- 2005
It is shown that morphine does cause short-term desensitization, and whole-cell recordings from neurons in the locus ceruleus are used to measure the potassium current induced by morphine, suggesting that morphine, like other agonists, can initiate receptor desensitized to decrease signaling.
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