Role of intracellulare endothelin-converting enzyme-1 (ECE-1) as a regulator of neuropeptide function and signalling in the skin

点击翻译按钮获取中文摘要

Recent studies indicate that a variety of peptidases play an important part in the control of neurogenic inflammation. We have recently described a new mechanism showing that endothelinconverting enzyme-1 (ECE-1) cleaves and inactivates substance P in acidified endosomes, thereby freeing β-arrestins from the neurokinin 1 receptor (NK1R), which recycles to mediate receptor resensitization or signalling. Thus, peptidases such as ECE-1 may have important implications in the regulation of neurogenic inflammation and neuronal diseases by controlling neuropeptide receptor resensitization. This implicates that inhibitors of ECE-1 may be beneficial for the treatment of inflammation, pain and other neuronal/psychiatric disorders. The aim of this study will be to determine the precise mechanism of how ECE-1 regulates receptor resensitization in detail and investigates the role of ECE-1 in cutaneous inflammation.