丙戊酸钠减少肌醇生物合成。
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Shaltiel G,沙米尔,夏皮罗J,丁D,道尔顿E,比亚尔M,哈伍德AJ, Belmaker RH,格林伯格ML, Agam G
丙戊酸钠减少肌醇生物合成。
生物精神病学杂志。2004年12月1;56 (11):868 - 74。doi: 10.1016 / j.biopsych.2004.08.027。
- PubMed ID
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15576064 (在PubMed]
- 文摘
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背景:锂和丙戊酸钠(VPA)用于治疗双相情感障碍。情绪稳定的机理尚未阐明,但肌醇的作用得到了实质性的支持。抑制肌醇monophosphatase锂,肌醇回收和从头合成所需的酶,建议锂耗尽脑肌醇的假设和变弱磷酸肌醇信号。丙戊酸钠也耗尽肌醇酵母,盘基网柄菌和鼠神经元。这种提高的可能性效应是myo-inositol-1-phosphate的结果(MIP)合酶抑制。方法:肌醇是通过气相色谱法来衡量的。人类前额叶皮层MIP合成酶活性原油匀浆中化验。INO1被Northern评估。生长锥形态学评估在培养大鼠神经元。结果:我们发现老鼠体内的肌醇20%急性VPA政府后额叶皮质。 As hypothesized, inositol reduction resulted from decreased MIP synthase activity: .21-.28 mmol/LVPA reduced the activity by 50%. Among psychotropic drugs, the effect is specific to VPA. Accordingly, only VPA upregulates the yeast INO1 gene coding for MIP synthase. The VPA derivative N-methyl-2,2,3,3,-tetramethyl-cyclopropane carboxamide reduces MIP synthase activity and has an affect similar to that of VPA on rat neurons, whereas another VPA derivative, valpromide, poorly affects the activity and has no affect on neurons. CONCLUSIONS: The rate-limiting step of inositol biosynthesis, catalyzed by MIP synthase, is inhibited by VPA; inositol depletion is a first event shown to be common to lithium and VPA.
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