Richardson U Ingrid, Watkins Carol J, Pierre Celine, Ulus Ismael H, Wurtman Richard J
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Brain Res. 2003 May 9;971(2):161-7. doi: 10.1016/s0006-8993(03)02333-3.
Oral administration of CDP-choline to rats raises plasma and brain cytidine levels and increases brain levels of phosphatidylcholine (PC). In contrast, in humans oral CDP-choline increases plasma levels of uridine. To determine whether uridine can also enhance PC synthesis, we developed an assay for CDP-choline, an immediate and rate-limiting precursor in PC synthesis, and measured this intermediate in clonal PC12 rat pheochromocytoma cells incubated with various concentrations of uridine or cytidine. Addition of uridine (50-100 microM) to the incubation medium caused significant elevations in UTP, CT, USAP and CDP-choline levels in PC12 cells. Uridine had no effect on the synthesis of diacylglycerol (DAG) or the activity of the phosphotransferase which catalyzes the synthesis of PC from DAG and CDP-choline. Hence uridine treatment was unlikely to inhibit the conversion of endogenous CDP-choline to PC. These results suggest the possibility that uridine may also enhance PC synthesis in intact brain.
给大鼠口服胞磷胆碱可提高血浆和脑内胞苷水平,并增加脑内磷脂酰胆碱(PC)水平。相比之下,在人类中口服胞磷胆碱会增加尿苷的血浆水平。为了确定尿苷是否也能增强PC合成,我们开发了一种检测PC合成中直接且限速前体胞磷胆碱的方法,并在与不同浓度尿苷或胞苷孵育的克隆PC12大鼠嗜铬细胞瘤细胞中测量了这种中间体。向孵育培养基中添加尿苷(50 - 100 microM)会导致PC12细胞中UTP、CT、USAP和胞磷胆碱水平显著升高。尿苷对二酰基甘油(DAG)的合成或催化由DAG和胞磷胆碱合成PC的磷酸转移酶活性没有影响。因此,尿苷处理不太可能抑制内源性胞磷胆碱向PC的转化。这些结果提示尿苷也可能增强完整脑内PC合成的可能性。