μ-Opioid receptor desensitization by β-arrestin-2 determines morphine tolerance but not dependence

By L. Bohn, R. Gainetdinov, F. Lin, R. J. Lefkowitz, M. Caron. Nature, 2000

828 citations recorded by the source corpus.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/2ce3e498b18dfbb12fd79237ff29a78666be43c9

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. R. Gainetdinov
2. J. Beaulieu
3. M. von Zastrow
4. L. Luttrell
5. R. J. Lefkowitz

In Molecular Biology

1. R. J. Lefkowitz
2. M. von Zastrow
3. R. Gainetdinov
4. J. Beaulieu
5. L. Luttrell
6. S. Dewire
7. Sudha K. Shenoy

Citations in the corpus

• Regulation of µ-Opioid Receptors: Desensitization, Phosphorylation, Internalization, and Tolerance (2013, background): “, 2011) and for GTPgS binding in brainstem tissue (Bohn et al., 2000) are consistent with this idea, but tolerance to other agonists has not yet been tested.”
• The Physiology, Signaling, and Pharmacology of Dopamine Receptors (2011, background): “In an initial study, -arrestin 2-deficient mice were found to exhibit enhanced morphine-induced analgesia compared with WT mice, which indicates that -arrestin 2 plays an important role in -opioid receptor desensitization (Bohn et al., 1999, 2000, 2003, 2004).”
• The role of beta-arrestins in the termination and transduction of G-protein-coupled receptor signals. (2002, background): “…with an inability to develop tolerance to the antinociceptive effects of morphine, but does not prevent the development of opioid dependence (Bohn et al., 2000). β-arrestins in GPCR sequestration Internalization of GPCRs, also termed receptor sequestration or endocytosis, occurs more slowly…”
• A G Protein-Biased Ligand at the μ-Opioid Receptor Is Potently Analgesic with Reduced Gastrointestinal and Respiratory Dysfunction Compared with Morphine (2013, background): “While these facets of MOR pharmacology will be explored with TRV130 in future studies, several of the previous studies of morphine in b-arrestin-2 knockout mice suggest that TRV130 may have reduced potential for addiction and analgesic tolerance (Bohn et al., 2000; Bohn et al., 2003; Raehal and Bohn”