The role of D-aspartic acid and N-methyl-D-aspartic acid in the regulation of prolactin release.
The role of D-aspartic acid and N-methyl-D-aspartic acid in the regulation of prolactin release.
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DOI：
10.1210/endo.141.10.7706
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发表时间：
2000-10
期刊：
影响因子：
4.8
通讯作者：
G. D'aniello;A. Tolino;A. D’Aniello;F. Errico;G. Fisher;M. M. Di Fiore-M.
中科院分区：
文献类型：
--
作者：
G. D'aniello;A. Tolino;A. D’Aniello;F. Errico;G. Fisher;M. M. Di Fiore-M.
在这项研究中，我们使用酶促HPLC方法结合D-天冬氨酸氧化酶，证明N-甲基-D-天冬氨酸（NMDA）作为一种天然化合物以纳摩尔水平存在于大鼠神经系统和内分泌腺中，并且在体内和体外生物合成。 D-天冬氨酸 (D-Asp) 是其天然前体，也是一种内源性化合物。在内分泌腺中，腺垂体中 D-Asp (78 +/- 12 nmol/g) 和 NMDA (8.4 +/- 1.2 nmol/g) 的含量最高，而下丘脑代表神经系统中这些氨基酸最丰富的区域（D-Asp 和 NMDA 为 55 +/- 9 和 5.6 +/- 1.1 nmol/g， 分别）。当大鼠通过腹腔注射D-Asp时，腺垂体大量摄取D-Asp，并且腺垂体、下丘脑和海马中NMDA的浓度显着增加，表明D-Asp是NMDA生物合成的内源性前体。对组织匀浆进行的实验证实，D-Asp 是 NMDA 的前体，并且催化该反应的酶是甲基转移酶。 S-腺苷-L-甲硫氨酸（SAM）是甲基供体。由腹膜内注射 D-天冬氨酸钠组成的体内实验表明，这种氨基酸诱导血清 PRL 显着升高，并且这种效应是剂量和时间依赖性的。对分离的腺垂体或与下丘脑联合的腺垂体进行的体外实验表明，PRL 的释放是由 D-Asp 对垂体的直接作用引起的，也是由 NMDA 对下丘脑的间接作用介导的。然后，后者诱导一种推定因子的释放，进而刺激腺垂体，增强 PRL 的释放。总之，我们的数据表明 D-Asp 和 NMDA 内源性存在于大鼠体内，并参与 PRL 释放的调节。
In this study, using an enzymatic HPLC method in combination with D-aspartate oxidase, we show that N-methyl-D-aspartate (NMDA) is present at nanomolar levels in rat nervous system and endocrine glands as a natural compound, and it is biosynthesized in vivo and in vitro. D-aspartate (D-Asp) is its natural precursor and also occurs as an endogenous compound. Among the endocrine glands, the highest quantities of D-Asp (78 +/- 12 nmol/g) and NMDA (8.4 +/- 1.2 nmol/g) occur in the adenohypophysis, whereas the hypothalamus represents the area of the nervous system where these amino acids are most abundant (55 +/- 9 and 5.6 +/- 1.1 nmol/g for D-Asp and NMDA, respectively). When D-Asp is administered to rats by ip injection, there is a significant uptake of D-Asp into the adenohypophysis and a significant increase in the concentration of NMDA in the adenohypophysis, hypothalamus and hippocampus, suggesting that D-Asp is an endogenous precursor for NMDA biosynthesis. Experiments conducted on tissue homogenates confirm that D-Asp is the precursor of the NMDA and that the enzyme catalyzing this reaction is a methyltransferase. S-adenosyl-L-methionine (SAM) is the methyl group donor. In vivo experiments consisting of ip injections of sodium D-aspartate show that this amino acid induced a significant serum PRL elevation and this effect is dose and time dependent. In vitro experiments conducted on isolated adenohypophysis or adenohypophysis coincubated with the hypothalamus, showed that the release of PRL is caused by a direct action of D-Asp on the pituitary gland and also mediated by the indirect action of NMDA on the hypothalamus. Then, the latter induces the release of a putative factor that in turn stimulates the adenohypophysis reinforcing the PRL release. In conclusion, our data suggest that D-Asp and NMDA are present endogenously in the rat and are involved in the modulation of PRL release.