| Autor: |
Zhuo GY; Institute of Translational Medicine and New Drug Development, China Medical University, Taichung 40402, Taiwan., Chen MC; Institute of Translational Medicine and New Drug Development, China Medical University, Taichung 40402, Taiwan., Lin TY; Center for Drug Abuse and Addiction, China Medical University Hospital, Taichung 40447, Taiwan., Lin ST; Integrative Stem Cell Center, China Medical University Hospital, Taichung 40447, Taiwan., Chen DT; School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.; Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan., Lee CW; Center for Drug Abuse and Addiction, China Medical University Hospital, Taichung 40447, Taiwan.; Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan. |
| Abstrakt: |
We attempted to examine the alterations elicited by opioids via coexpressed μ-opioid (MOP) and nociceptin/orphanin FQ (NOP) receptors for receptor localization and Erk1/2 (p44/42 MAPK) in human embryonic kidney (HEK) 293 cells. Through two-photon microscopy, the proximity of MOP and NOP receptors was verified by fluorescence resonance energy transfer (FRET), and morphine but not buprenorphine facilitated the process of MOP-NOP heterodimerization. Single-particle tracking (SPT) further revealed that morphine or buprenorphine hindered the movement of the MOP-NOP heterodimers. After exposure to morphine or buprenorphine, receptor localization on lipid rafts was detected by immunocytochemistry, and phosphorylation of Erk1/2 was determined by immunoblotting in HEK 293 cells expressing MOP, NOP, or MOP+NOP receptors. Colocalization of MOP and NOP on lipid rafts was enhanced by morphine but not buprenorphine. Morphine stimulated the phosphorylation of Erk1/2 with a similar potency in HEK 293 cells expressing MOP and MOP+NOP receptors, but buprenorphine appeared to activate Erk1/2 solely through NOP receptors. Our results suggest that opioids can fine-tune the cellular localization of opioid receptors and phosphorylation of Erk1/2 in MOP+NOP-expressing cells. |
