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着重要作用。我们最近描述了一种新的机制，表明内皮素转换酶-1 （ECE-1）在酸化的核内体中分裂和失活P物质，从而从神经激肽1受体（NK1R）中释放β-抑制素，该受体循环介导受体再敏或信号传导。因此，像ECE-1这样的肽酶可能通过控制神经肽受体重敏在神经源性炎症和神经元疾病的调节中具有重要意义。这意味着ECE-1抑制剂可能对炎症、疼痛和其他神经/精神疾病的治疗有益。本研究的目的是详细确定ECE-1调节受体再敏化的确切机制，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.