High-affinity enkephalin-degrading peptidase in brain is increased after morphine
High-affinity enkephalin-degrading peptidase in brain is increased after morphine
复制标题
吗啡后大脑中高亲和力脑啡肽降解肽酶增加
作者：
B. Malfroy;J. Swerts;A. Guyon;B. Roques;J. Schwartz
现在有大量证据表明，内源性阿片五肽Met-脑啡肽（Tyr-Gly-Gly-Phe-Met）和Leu-脑啡肽（Tyr-Gly-Gly-Phe-Leu）在中枢神经系统中起神经递质的作用。这一假说的一个相关点是，一种特定的失活机制必须在阿片受体附近起作用，以迅速关闭脑啡肽信号。事实上，最近的研究表明，五肽在各种组织中会非常迅速地失活，主要是通过Tyr-Gly酰胺键的断裂1 -5发生。这一特征解释了这些肽的短暂生物活性，与合成类似物如（D-Ala 2）-Met-脑啡酰胺的有效活性形成对比，其中该键受到保护6。然而，包括脑在内的许多组织含有一系列特异性和亲和力较低的肽酶7，尚未提供证据表明特定酶参与脑啡肽能传递的调节。我们现在报告的存在下，高亲和力的肽酶在小鼠纹状体的颗粒部分分裂Leu-脑啡肽分子释放的三肽片段（Tyr-Gly-Gly），并表现出明确的底物特异性。长期用吗啡处理的小鼠纹状体中这种肽酶活性的显著和选择性增加表明它可能与脑啡肽能传递有关。
CONSIDERABLE evidence now exists to suggest that the endogenous opioid pentapeptides Met-enkephalin (Tyr-Gly-Gly-Phe-Met) and Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) function as neurotransmitters in the central nervous system. A correlate of this hypothesis is that a specific inactivation mechanism must operate in the vicinity of opiate receptors to turn off rapidly the enkephalin signal. Indeed recent studies have shown that the pentapeptides are subject to extremely rapid inactivation in various tissues, occurring primarily by cleavage of the Tyr–Gly amide bond1–5. This feature accounts for the short-lasting biological activity of these peptides, contrasting with the potent activity of synthetic analogues such as (D-Ala2)-Met-enkephalinamide in which this bond is protected6. However, many tissues including brain contain a spectrum of peptidases with low specificities and affinities7 and no evidence has been yet provided for the involvement of a specific enzyme in the regulation of enkephalinergic transmission. We now report the presence of a high-affinity peptidase in a particulate fraction of mouse striatum splitting the Leu-enkephalin molecule with release of a tripeptide fragment (Tyr-Gly-Gly) and exhibiting definite substrate specificity. The marked and selective increase in the activity of this peptidase in the striatum of mice chronically treated with morphine suggests that it might be associated with enkephalinergic transmission.