Occurrence of D-aspartic acid and N-methyl-D-aspartic acid in rat neuroendocrine tissues and their role in the modulation of luteinizing hormone and growth hormone release
Occurrence of D-aspartic acid and N-methyl-D-aspartic acid in rat neuroendocrine tissues and their role in the modulation of luteinizing hormone and growth hormone release
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DOI：
10.1096/fasebj.14.5.699
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发表时间：
2000-04-01
期刊：
影响因子：
4.8
通讯作者：
Ingrosso, D
中科院分区：
文献类型：
--
作者：
D'Aniello, A;Di Fiore, MM;Ingrosso, D
使用两个特定的和敏感的荧光/HPLC方法和GC-MS方法，单独和与D-天冬氨酸氧化酶相结合，我们已经证明了第一次，N-甲基-D-天冬氨酸（NMDA），除了D-天冬氨酸（D-Asp），是内源性存在的天然分子在大鼠神经系统和内分泌腺。这两种氨基酸在腺垂体、下丘脑、脑和睾丸中主要以nmol/g水平浓缩。腺垂体最大限度地表现出积累D-Asp的能力时，后者是外源性管理。在体内实验中，包括腹腔注射D-Asp，表明D-Asp诱导生长激素和黄体生成素（LH）的释放。然而，体外实验表明，D-Asp能够诱导LH释放腺垂体只有当这个腺体与下丘脑共孵育。这是因为D-Asp还诱导下丘脑释放GnRH，而下丘脑又直接负责D-Asp诱导的垂体LH分泌。与D-Asp相比，NMDA在比D-Asp低100倍的浓度下就能发挥其激素释放作用。特异性NMDA受体拮抗剂D-AP 5抑制D-Asp和NMDA激素活性，表明这些作用是由NMDA受体介导的。NMDA通过S-腺苷甲硫氨酸依赖性酶从D-Asp生物合成，我们暂时命名为NMDA合酶。D'Aniello，A.，Di Fiore，M. M.的情况，Fisher，G. H.，米隆，A.，Seleni，A.，D'Aniello，S.，佩尔纳，A. F.、Ingrosso，D. D-天冬氨酸和N-甲基-D-天冬氨酸在大鼠神经内分泌组织中的存在及其对促黄体生成素和生长激素释放的调节作用
Using two specific and sensitive fluorometric/HPLC methods and a GC-MS method, alone and in combination with D-aspartate oxidase, we have demonstrated for the first time that N-methyl-D-aspartate (NMDA), in addition to D-aspartate (D-Asp), is endogenously present as a natural molecule in rat nervous system and endocrine glands. Both of these amino acids are mostly concentrated at nmol/g levels in the adenohypophysis, hypothalamus, brain, and testis. The adenohypophysis maximally showed the ability to accumulate D-Asp when the latter is exogenously administered. In vivo experiments, consisting of the i.p. injection of D-Asp, showed that D-Asp induced both growth hormone and luteinizing hormone (LH) release. However, in vitro experiments showed that D-Asp was able to induce LH release from adenohypophysis only when this gland was co-incubated with the hypothalamus. This is because D-Asp also induces the release of GnRH from the hypothalamus, which in turn is directly responsible for the D-Asp-induced LH secretion from the pituitary gland. Compared to D-Asp, NMDA elicits its hormone release action at concentrations similar to 100-fold lower than D-Asp. D-AP5, a specific NMDA receptor antagonist, inhibited D-Asp and NMDA hormonal activity, demonstrating that these actions are mediated by NMDA receptors. NMDA is biosynthesized from D-Asp by an S-adeno- sylmethionine-dependent enzyme, which we tentatively denominated as NMDA synthase.-D'Aniello, A., Di Fiore, M. M., Fisher, G. H., Milone, A., Seleni, A., D'Aniello, S., Perna, A. F., Ingrosso, D. Occurrence of D-aspartic acid and N-methyl-D-aspartic acid in rat neuroendocrine tissues and their role in the modulation of luteinizing hormone and growth hormone release.