Opioid receptor function is regulated by post-endocytic peptide processing.

摘要: Most neuroendocrine peptides are generated in the secretory compartment by proteolysis of precursors at classical cleavage sites consisting basic residues well studied endopeptidases belonging to subtilisin superfamily. In contrast, a subset bioactive is processing non-classical that do not contain residues. Neither peptidases responsible for cleavages nor involved such has been established. Members endothelin-converting enzyme (ECE) family considered good candidate enzymes because they exhibit functional properties consistent with role. this study we have explored role ECE2 endocytic δ opioid and its effect on modulating receptor function using selective inhibitors had identified previously homology modeling virtual screening library small molecules. We found agonist treatment led intracellular co-localization receptors. Furthermore, reagents increase pH acidic impaired recycling protecting endocytosed peptide from degradation. This, turn, substantial decrease surface signaling. Finally, showed primary neurons inhibitor during increased receptors ECE2, which turn decreased signaling Together, these results support differential modulation post-endocytic agonists ECE2.