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Sci. Signal., 20 July 2010
Vol. 3, Issue 131, p. ra54
[DOI: 10.1126/scisignal.2000807]


Editor's Summary

Drug-Induced Heteromers
Opioid receptors are G protein–coupled receptors and are divided into µ, {delta}, and {kappa} subtypes. Homomers of µ or {delta} receptors signal through a G{alpha}i-mediated pathway; however, these receptor subtypes can also form heteromers that signal through G{alpha}z- or β-arrestin2–mediated pathways. Although morphine analgesia is mediated primarily through the µ receptor, {delta} receptor ligands can potentiate µ receptor–mediated signaling, suggesting that the µ-{delta} heteromer may also be involved in morphine analgesia. Gupta et al. developed an antibody that selectively recognizes µ-{delta} heteromers and found that the abundance of the µ-{delta} heteromer in mice increased with chronic administration of morphine. These increases were detected in regions of the brain that are involved in the modulation of pain transmission. These results suggest that the µ-{delta} heteromer may be a candidate for therapies to alleviate chronic pain syndromes.

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).

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