Sato Kaoru, Saito Yoshihiko, Oka Jun-ichiro, Ohwada Tomohiko, Nakazawa Ken
Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan.
J Pharmacol Sci. 2008 Jun;107(2):226-30. doi: 10.1254/jphs.08039sc. Epub 2008 Jun 10.
Tamoxifen (Tam) decreased the clearance of L-glutamate (L-Glu) by cultured astrocytes at 1 pM, 1 nM, and 1 microM, but became toxic at 10 microM. When L-Glu transporters were mostly inhibited by threo-beta-benzyloxyaspartate (TBOA) (1 mM) or D,L-threo-beta-hydroxyaspartate (THA) (1 mM), Tam (1 nM) did not change extracellular L-Glu concentration, confirming that Tam attenuates L-Glu transport through L-Glu transporters. ICI182,780, LY294002, and U0126 inhibited the effect of Tam dose-dependently, suggesting the involvement of estrogen receptors (ERs), the phosphatidylinositol 3-kinase (PI3K) cascade, and the mitogen-activated protein kinase (MAPK) cascade in the effect of Tam.
他莫昔芬（Tam）在1皮摩尔、1纳摩尔和1微摩尔浓度下可降低培养星形胶质细胞对L-谷氨酸（L-Glu）的清除率，但在10微摩尔时具有毒性。当L-谷氨酸转运体大多被苏式-β-苄氧基天冬氨酸（TBOA）（1毫摩尔）或D，L-苏式-β-羟基天冬氨酸（THA）（1毫摩尔）抑制时，Tam（1纳摩尔）不会改变细胞外L-谷氨酸浓度，证实Tam通过L-谷氨酸转运体减弱L-谷氨酸转运。ICI182,780、LY294002和U0126剂量依赖性地抑制Tam的作用，提示雌激素受体（ERs）、磷脂酰肌醇3激酶（PI3K）级联和丝裂原活化蛋白激酶（MAPK）级联参与了Tam的作用。
