神経細胞におけるオピオイド受容体活性化による受容体シャペロン分子 RTP4 の発現制御

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  • Regulation of receptor chaperone molecule RTP4 in neuronal cells by opioid receptor activation

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<p>Receptor transporter protein family members (RTP1-4) are known to promote the trafficking of G-protein coupled receptor to the cell surface membrane. Recent studies have shown that RTP4 interacts with mu opioid receptor-delta opioid receptor (MOPr-DOPr) heteromers and this leads to increase of the MOPr-DOPr heteromer levels at the cell surface after MOPr stimulation. In this study we explored the regulation of RTP4 expression by MOPr stiumlation and its mechanism. We treated Neuro2a cells that express MOPr and DOPr with DAMGO (MOPr ligand) found that DAMGO stimulation induces significant increase in RTP4 mRNA levels. By using several inhibitors of signaling molecules, we find that DAMGO-induced increase in RTP4 expression can be blocked by pre-treatment with the receptor-selective antagonist, Gai inhibitor, transcription inhibitor, and MEK inhibitor, while PKC inhibitor did not affect. Interestingly, JAK inhibitor also exhibited trend to decrease the effect of DAMGO. Together, these results suggest the expression of RTP4 is upregulated by MOPr activation via G-protein, MEK and/or JAK mediated pathways, and this, in turn, is likely to enhance the cell surface expression of MOPr-DOPr heteromers.</p>

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