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Science 286 (5449): 2495-2498

Copyright © 1999 by the American Association for the Advancement of Science

Enhanced Morphine Analgesia in Mice Lacking beta -Arrestin 2 

Laura M. Bohn, 1* Robert J. Lefkowitz, 2dagger ddagger Raul R. Gainetdinov, 1 Karsten Peppel, 2 Marc G. Caron, 1dagger Fang-Tsyr Lin 2*

The ability of morphine to alleviate pain is mediated through a heterotrimeric guanine nucleotide binding protein (G protein)-coupled heptahelical receptor (GPCR), the µ opioid receptor (µOR). The efficiency of GPCR signaling is tightly regulated and ultimately limited by the coordinated phosphorylation of the receptors by specific GPCR kinases and the subsequent interaction of the phosphorylated receptors with beta -arrestin 1 and beta -arrestin 2. Functional deletion of the beta -arrestin 2 gene in mice resulted in remarkable potentiation and prolongation of the analgesic effect of morphine, suggesting that µOR desensitization was impaired. These results provide evidence in vivo for the physiological importance of beta -arrestin 2 in regulating the function of a specific GPCR, the µOR. Moreover, they suggest that inhibition of beta -arrestin 2 function might lead to enhanced analgesic effectiveness of morphine and provide potential new avenues for the study and treatment of pain, narcotic tolerance, and dependence.

1 Howard Hughes Medical Institute Laboratories, Departments of Cell Biology and Medicine,
2 Howard Hughes Medical Institute Laboratories, Departments of Biochemistry and Medicine, Duke University Medical Center, Durham, NC 27710, USA.
*   These authors contributed equally to this report.

dagger    To whom correspondence should be addressed. E-mail: lefko001{at}receptor-biol.duke.edu; or caron002{at}mc.duke.edu

ddagger    To whom requests for materials should be addressed.

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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A. Dahan, A. Yassen, R. Romberg, E. Sarton, L. Teppema, E. Olofsen, and M. Danhof (2006)
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   Abstract »    Full Text »    PDF »
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Y. Su, S. K. Raghuwanshi, Y. Yu, L. B. Nanney, R. M. Richardson, and A. Richmond (2005)
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   Abstract »    Full Text »    PDF »
Morphine Side Effects in {beta}-Arrestin 2 Knockout Mice.
K. M. Raehal, J. K. L. Walker, and L. M. Bohn (2005)
J. Pharmacol. Exp. Ther. 314, 1195-1201
   Abstract »    Full Text »    PDF »
The Role of Opioid Receptor Internalization and {beta}-Arrestins in the Development of Opioid Tolerance.
Z. Zuo (2005)
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   Abstract »    Full Text »    PDF »
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A. Palmitessa, H. A. Hess, I. A. Bany, Y.-M. Kim, M. R. Koelle, and J. L. Benovic (2005)
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   Abstract »    Full Text »    PDF »
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M. Pi, R. H. Oakley, D. Gesty-Palmer, R. D. Cruickshank, R. F. Spurney, L. M. Luttrell, and L. D. Quarles (2005)
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   Abstract »    Full Text »    PDF »
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S. L. Ferrari, D. D. Pierroz, V. Glatt, D. S. Goddard, E. N. Bianchi, F. T. Lin, D. Manen, and M. L. Bouxsein (2005)
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   Abstract »    Full Text »    PDF »
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S. P. Hack, E. E. Bagley, B. C. H. Chieng, and M. J. Christie (2005)
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   Abstract »    Full Text »    PDF »
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C. Krasel, M. Bunemann, K. Lorenz, and M. J. Lohse (2005)
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   Abstract »    Full Text »    PDF »
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A. Bradaia, F. Berton, S. Ferrari, and C. Luscher (2005)
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   Abstract »    Full Text »    PDF »
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T. Koch, A. Widera, K. Bartzsch, S. Schulz, L.-O. Brandenburg, N. Wundrack, A. Beyer, G. Grecksch, and V. Hollt (2005)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
Relative Opioid Efficacy Is Determined by the Complements of the G Protein-Coupled Receptor Desensitization Machinery.
L. M. Bohn, L. A. Dykstra, R. J. Lefkowitz, M. G. Caron, and L. S. Barak (2004)
Mol. Pharmacol. 66, 106-112
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Spinophilin Blocks Arrestin Actions in Vitro and in Vivo at G Protein-Coupled Receptors.
Q. Wang, J. Zhao, A. E. Brady, J. Feng, P. B. Allen, R. J. Lefkowitz, P. Greengard, and L. E. Limbird (2004)
Science 304, 1940-1944
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Reduced GRK2 level in T cells potentiates chemotaxis and signaling in response to CCL4.
A. Vroon, C. J. Heijnen, M. S. Lombardi, P. M. Cobelens, F. Mayor Jr, M. G. Caron, and A. Kavelaars (2004)
J. Leukoc. Biol. 75, 901-909
   Abstract »    Full Text »    PDF »
Prolonged Kappa Opioid Receptor Phosphorylation Mediated by G-protein Receptor Kinase Underlies Sustained Analgesic Tolerance.
J. P. McLaughlin, L. C. Myers, P. E. Zarek, M. G. Caron, R. J. Lefkowitz, T. A. Czyzyk, J. E. Pintar, and C. Chavkin (2004)
J. Biol. Chem. 279, 1810-1818
   Abstract »    Full Text »    PDF »
The Unique Amino-terminal Region of the PDE4D5 cAMP Phosphodiesterase Isoform Confers Preferential Interaction with {beta}-Arrestins.
G. B. Bolger, A. McCahill, E. Huston, Y.-F. Cheung, T. McSorley, G. S. Baillie, and M. D. Houslay (2003)
J. Biol. Chem. 278, 49230-49238
   Abstract »    Full Text »    PDF »
Enhanced Rewarding Properties of Morphine, but not Cocaine, in {beta}arrestin-2 Knock-Out Mice.
L. M. Bohn, R. R. Gainetdinov, T. D. Sotnikova, I. O. Medvedev, R. J. Lefkowitz, L. A. Dykstra, and M. G. Caron (2003)
J. Neurosci. 23, 10265-10273
   Abstract »    Full Text »    PDF »
The Adaptor Protein {beta}-Arrestin2 Enhances Endocytosis of the Low Density Lipoprotein Receptor.
J.-H. Wu, K. Peppel, C. D. Nelson, F.-T. Lin, T. A. Kohout, W. E. Miller, S. T. Exum, and N. J. Freedman (2003)
J. Biol. Chem. 278, 44238-44245
   Abstract »    Full Text »    PDF »
{beta}-Arrestin 2 Mediates Endocytosis of Type III TGF-{beta} Receptor and Down-Regulation of Its Signaling.
W. Chen, K. C. Kirkbride, T. How, C. D. Nelson, J. Mo, J. P. Frederick, X.-F. Wang, R. J. Lefkowitz, and G. C. Blobe (2003)
Science 301, 1394-1397
   Abstract »    Full Text »    PDF »
G-protein-coupled Receptor (GPCR) Kinase Phosphorylation and {beta}-Arrestin Recruitment Regulate the Constitutive Signaling Activity of the Human Cytomegalovirus US28 GPCR.
W. E. Miller, D. A. Houtz, C. D. Nelson, P. E. Kolattukudy, and R. J. Lefkowitz (2003)
J. Biol. Chem. 278, 21663-21671
   Abstract »    Full Text »    PDF »
G Protein-independent G1 Cell Cycle Block and Apoptosis with Morphine in Adenocarcinoma Cells: Involvement of p53 Phosphorylation.
I. Tegeder, S. Grosch, A. Schmidtko, A. Haussler, H. Schmidt, E. Niederberger, K. Scholich, and G. Geisslinger (2003)
Cancer Res. 63, 1846-1852
   Abstract »    Full Text »    PDF »
Up-Regulation of Regulator of G Protein Signaling 4 Expression in a Model of Neuropathic Pain and Insensitivity to Morphine.
M. Garnier, P. F. Zaratin, G. Ficalora, M. Valente, L. Fontanella, M.-H. Rhee, K. J. Blumer, and M. A. Scheideler (2003)
J. Pharmacol. Exp. Ther. 304, 1299-1306
   Abstract »    Full Text »    PDF »
Regulation of G Protein-Coupled Receptor Kinases and Arrestins During Receptor Desensitization.
T. A. Kohout and R. J. Lefkowitz (2003)
Mol. Pharmacol. 63, 9-18
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Genetic Dissociation of Opiate Tolerance and Physical Dependence in delta -Opioid Receptor-1 and Preproenkephalin Knock-Out Mice.
J. F. Nitsche, A. G. P. Schuller, M. A. King, M. Zengh, G. W. Pasternak, and J. E. Pintar (2002)
J. Neurosci. 22, 10906-10913
   Abstract »    Full Text »    PDF »
beta -Arrestin2 Is Critically Involved in CXCR4-mediated Chemotaxis, and This Is Mediated by Its Enhancement of p38 MAPK Activation.
Y. Sun, Z. Cheng, L. Ma, and G. Pei (2002)
J. Biol. Chem. 277, 49212-49219
   Abstract »    Full Text »    PDF »
Chronic Morphine Treatment Inhibits Opioid Receptor Desensitization and Internalization.
D. A. Eisinger, H. Ammer, and R. Schulz (2002)
J. Neurosci. 22, 10192-10200
   Abstract »    Full Text »    PDF »
Differential Mechanisms of Morphine Antinociceptive Tolerance Revealed in beta Arrestin-2 Knock-Out Mice.
L. M. Bohn, R. J. Lefkowitz, and M. G. Caron (2002)
J. Neurosci. 22, 10494-10500
   Abstract »    Full Text »    PDF »

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