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

最近的研究表明，多种肽酶在神经源性炎症的控制中起重要作用。我们最近描述了一种新的机制，表明内皮素转换酶-1（ECE-1）在酸化的核内体中切割并灭活P物质，从而从神经激肽1受体（NK 1 R）中释放β-arrestins，NK 1 R介导受体再敏化或信号传导。因此，肽酶，如ECE-1可能有重要的影响，在调节神经源性炎症和神经元疾病，通过控制神经肽受体再敏感。这意味着ECE-1抑制剂可能有益于治疗炎症、疼痛和其他神经元/精神疾病。本研究的目的是详细确定ECE-1如何调节受体再敏感的确切机制，并研究ECE-1在皮肤炎症中的作用。

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.