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Neuropeptide-Mediated Receptor Trafficking

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Science  09 Sep 2005:
Vol. 309, Issue 5741, pp. 1653
DOI: 10.1126/science.309.5741.1653c

Opioid receptors on pain-sensing neurons mediate the inhibitory effects of opiates on pain. The δ-opioid receptor, which is sorted into large dense-core vesicles (LDCVs) that carry secreted neuropeptides, is inserted into the membrane in response to opioid agonists or neuronal firing. Guan et al. noted that, in dorsal root ganglion neurons containing substance P, δ-opioid receptors colocalized with the neurotransmitter substance P in LDCVs, but in mice lacking preprotachykinin A gene, which encodes substance P and other tachykinin peptides, the receptors were absent from the vesicles. By expressing different portions of the substance P precursor, the authors determined that the δ-opioid receptor sorting signal was in the substance P domain and that sorting into LDCVs depended on the interaction of the signal with the third extracellular loop of the opioid receptor. Stimulus-dependent membrane insertion of the δ-opioid receptor was attenuated in preprotachykinin A-knockout mice, and both δ-opioid receptor-mediated spinal analgesia and morphine tolerance were eliminated. Thus, these results suggest an intriguing link between pain pathways (substance P) and analgesia (opioid receptor). — EMA

Cell 122, 619 (2005).

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