Endothelin‐converting enzyme 2 differentially regulates opioid receptor activity

摘要: Background and Purpose Opioid receptor function is modulated by post-activation events such as endocytosis, recycling and/or degradation. While it generally understood that the peptide ligand gets co-endocytosed with receptor, relatively few studies have investigated role of endocytosed processing enzymes in regulating function. In this study, we focused on endothelin-converting enzyme 2 (ECE2), a member neprilysin family metallopeptidases exhibits an acidic pH optimum, localizes to intracellular compartment selectively processes neuropeptides including opioid peptides vitro, examined its modulating μ resensitization. Experimental Approach The effect ECE2 inhibition hydrolysis was using thin-layer chromatography trafficking either elisa or microscopy. The signalling measured cAMP assay and, vivo, antinociception induced intrathecally administered opioids tail-flick assay. Key Results The highly selective inhibitor, S136492, significantly impaired only those ligands are substrates seen both heterologous cells endogenously co-expressing receptors ECE2. We also found attenuated mediated substrates. Conclusions Implications These results suggest ECE2, endogenous endocytic compartment, plays activity. Linked Articles This article part themed section Opioids: New Pathways Functional Selectivity. To view other articles visit http://dx.doi.org/10.1111/bph.2015.172.issue-2