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Sci. Signal., 20 July 2010
Vol. 3, Issue 131, p. ra54
[DOI: 10.1126/scisignal.2000807]
RESEARCH ARTICLES
Increased Abundance of Opioid Receptor Heteromers After Chronic Morphine Administration
Achla Gupta1,
Jan Mulder2,
Ivone Gomes1,
Raphael Rozenfeld1,
Ittai Bushlin1,
Edmund Ong3,
Maribel Lim1,
Emeline Maillet4,
Mats Junek3,
Catherine M. Cahill3,
Tibor Harkany2, and
Lakshmi A. Devi1,4*
1 Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA. 2 European Neuroscience Institute at Aberdeen, University of Aberdeen, Aberdeen AB252ZD, Scotland, UK. 3 Departments of Pharmacology and Toxicology, Queens University, Kingston, Ontario, Canada K7L 3N6. 4 Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, USA.
Abstract:
The µ and types of opioid receptors form heteromers that exhibit pharmacological and functional properties distinct from those of homomeric receptors. To characterize these complexes in the brain, we generated antibodies that selectively recognize the µ- heteromer and blocked its in vitro signaling. With these antibodies, we showed that chronic, but not acute, morphine treatment caused an increase in the abundance of µ- heteromers in key areas of the central nervous system that are implicated in pain processing. Because of its distinct signaling properties, the µ- heteromer could be a therapeutic target in the treatment of chronic pain and addiction.
* To whom correspondence should be addressed. E-mail: lakshmi.devi{at}mssm.edu
Citation: A. Gupta, J. Mulder, I. Gomes, R. Rozenfeld, I. Bushlin, E. Ong, M. Lim, E. Maillet, M. Junek, C. M. Cahill, T. Harkany, L. A. Devi, Increased Abundance of Opioid Receptor Heteromers After Chronic Morphine Administration. Sci. Signal.3, ra54 (2010).
Nancy R. Gough (24 April 2012) Sci. Signal.5 (221), ec116.
[DOI: 10.1126/scisignal.2003157] |Abstract »
EDITORS' CHOICE
Wei Wong (6 December 2011) Sci. Signal.4 (202), ec342.
[DOI: 10.1126/scisignal.4202ec342] |Abstract »
EDITORIAL GUIDES
Nancy R. Gough (9 August 2011) Sci. Signal.4 (185), eg7.
[DOI: 10.1126/scisignal.2002388] |Abstract »|Full Text »|PDF »
PERSPECTIVES
Nevin A. Lambert (30 March 2010) Sci. Signal.3 (115), pe12.
[DOI: 10.1126/scisignal.3115pe12] |Abstract »|Full Text »|PDF »
PERSPECTIVES
MacDonald J. Christie and Christophe Mallet (15 September 2009) Sci. Signal.2 (88), pe57.
[DOI: 10.1126/scisignal.288pe57] |Abstract »|Full Text »|PDF »
Novel Screening Assay for the Selective Detection of G-Protein-Coupled Receptor Heteromer Signaling.
R. M. van Rijn, J. H. Harvey, D. I. Brissett, J. N. DeFriel, and J. L. Whistler (2013)
J. Pharmacol. Exp. Ther.
344, 179-188
|Abstract »|Full Text »|PDF »
Functional Homomers and Heteromers of Dopamine D2L and D3 Receptors Co-exist at the Cell Surface.
C. Pou, C. Mannoury la Cour, L. A. Stoddart, M. J. Millan, and G. Milligan (2012)
J. Biol. Chem.
287, 8864-8878
|Abstract »|Full Text »|PDF »
Cys-27 Variant of Human {delta}-Opioid Receptor Modulates Maturation and Cell Surface Delivery of Phe-27 Variant via Heteromerization.
T. T. Leskela, J. J. Lackman, M. M. Vierimaa, H. Kobayashi, M. Bouvier, and U. E. Petaja-Repo (2012)
J. Biol. Chem.
287, 5008-5020
|Abstract »|Full Text »|PDF »
Chronic Methadone Treatment Shows a Better Cost/Benefit Ratio than Chronic Morphine in Mice.
J. Enquist, M. Ferwerda, L. Milan-Lobo, and J. L. Whistler (2012)
J. Pharmacol. Exp. Ther.
340, 386-392
|Abstract »|Full Text »|PDF »
Allosteric Interactions between {delta} and {kappa} Opioid Receptors in Peripheral Sensory Neurons.
K. A. Berg, M. P. Rowan, A. Gupta, T. A. Sanchez, M. Silva, I. Gomes, B. A. McGuire, P. S. Portoghese, K. M. Hargreaves, L. A. Devi, et al. (2012)
Mol. Pharmacol.
81, 264-272
|Abstract »|Full Text »|PDF »
Activation of Spinal {micro}- and {delta}-Opioid Receptors Potently Inhibits Substance P Release Induced by Peripheral Noxious Stimuli.
Heteromerization of the {micro}- and {delta}-Opioid Receptors Produces Ligand-Biased Antagonism and Alters {micro}-Receptor Trafficking.
L. Milan-Lobo and J. L. Whistler (2011)
J. Pharmacol. Exp. Ther.
337, 868-875
|Abstract »|Full Text »|PDF »
G Protein-Coupled Receptor Heteromerization: A Role in Allosteric Modulation of Ligand Binding.
I. Gomes, A. P. IJzerman, K. Ye, E. L. Maillet, and L. A. Devi (2011)
Mol. Pharmacol.
79, 1044-1052
|Abstract »|Full Text »|PDF »
A Unique Role of RGS9-2 in the Striatum as a Positive or Negative Regulator of Opiate Analgesia.
K. Psigfogeorgou, D. Terzi, M. M. Papachatzaki, A. Varidaki, D. Ferguson, S. J. Gold, and V. Zachariou (2011)
J. Neurosci.
31, 5617-5624
|Abstract »|Full Text »|PDF »