Quisqualate selectively inhibits a brain peptidase which cleaves N-acetyl-L-aspartyl-L-glutamate in vitro.
Quisqualate selectively inhibits a brain peptidase which cleaves N-acetyl-L-aspartyl-L-glutamate in vitro.
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Quisqualate 选择性抑制脑肽酶，该酶可在体外裂解 N-乙酰基-L-天冬氨酰-L-谷氨酸。
DOI：
10.1016/0014-2999(86)90291-8
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发表时间：
1986
影响因子：
5
通讯作者：
Coyle,JT
中科院分区：
文献类型：
--
作者：
Robinson,MB;Blakely,RD;Coyle,JT
内源性脑肽n -乙酰- l-天冬氨酸- l-谷氨酸（NAAG）已被认为是一种兴奋性神经递质（Coyle等，in press）。电生理、免疫细胞化学和病变研究都支持这种在侧嗅道中的作用（french- mullen等，1985；Blakely等，1986），一种假定的谷氨酸能通路。离子电泳应用NAAG的兴奋作用的快速终止表明，除扩散外，其他机制可能是其失活的原因。我们之前已经证明，在突触体与[3H] NAAG的孵育过程中，来自NAAG羧基末端的谷氨酸（Glu）被突触体主动隔离，而另一种裂解产物n -乙酰- l-天冬氨酸（NAA）显然没有被运输（Blakely等人，1986b）。来自NAAG的放射性标记Glu的运输被许多有效阻断Na+依赖性高亲和力Glu摄取（sdhgu）的化合物以相似的效力抑制。这两种转运过程的药理学特征之间的一个显著差异是前者对L-quisqualate （Quis）的高度敏感性，Quis是一种相当无效的shagu抑制剂。为了解释这些观察结果，我们假设存在一种肽酶活性，与
The endogenous brain peptide, N-acetyl-L-aspartyl-L-glutamate (NAAG), has been proposed as an excitatory neurotransmitter (Coyle et al., in press). Electrophysiological, immunocytochemical, and lesion studies support this role in the lateral olfactory tract (ffrench-Mullen et al., 1985; Blakely et al., 1986), a putative glutamatergic pathway. The rapid termination of the excitatory action of iontophoretically applied NAAG suggests that mechanism (s) other than diffusion likely account for its inactivation. We have previously demonstrated that, during incubation of synaptosomes with [3H] NAAG, glutamate (Glu) derived from the carboxy-terminus of NAAG is actively sequestered by synaptosomes while N-acetyl-L-aspartate (NAA), the other cleavage product, is apparently not transported (Blakely et al., 1986b). Transport of radiolabelled Glu derived from NAAG is inhibited with similar potency by many compounds that effectively block Na+-dependent, high affinity Glu uptake (SDHAGU). One striking difference between the pharmacological profiles of these two transport processes is a high sensitivity of the former process to L-quisqualate (Quis), a rather ineffective inhibitor of SDHAGU. To explain these observations, we postulated the existence of a peptidase activity, associated with