He SQ*, Zhang ZN*, Guan JS*, Liu HR, Zhao B, Wang HB, Li QA, Yang H, Luo J, Li ZY, Wang QO, Lu YJ, Bao L, Zhang X. Facilitation of μ-Opioid Receptor Activity by Preventing δ-Opioid Receptor-Mediated Co-Degradation. NEURON 69(1):120-131, 2011

root 提交于 周日, 10/31/2021 - 01:47
Abstract δ-opioid receptors (DORs) form heteromers with μ-opioid receptors (MORs) and negatively regulate MOR-mediated spinal analgesia. However, the underlying mechanism remains largely unclear. The present study shows that the activity of MORs can be enhanced by preventing MORs from DOR-mediated codegradation. Treatment with DOR-specific agonists led to endocytosis of both DORs and MORs. These receptors were further processed for ubiquitination and lysosomal degradation, resulting in a reduction of surface MORs. Such effects were attenuated by treatment with an interfering peptide containing the first transmembrane domain of MOR (MOR(TM1)), which interacted with DORs and disrupted the MOR/DOR interaction. Furthermore, the systemically applied fusion protein consisting of MOR(TM1) and ......

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