Ulus Ismail H, Watkins Carol J, Cansev Mehmet, Wurtman Richard J
Department of Pharmacology and Clinical Pharmacology, Uludag University Medical School, Bursa, Turkey.
Cell Mol Neurobiol. 2006 Jul-Aug;26(4-6):563-77. doi: 10.1007/s10571-006-9004-5. Epub 2006 Apr 25.
Treatments that increase acetylcholine release from brain slices decrease the synthesis of phosphatidylcholine by, and its levels in, the slices. We examined whether adding cytidine or uridine to the slice medium, which increases the utilization of choline to form phospholipids, also decreases acetylcholine levels and release.
We incubated rat brain slices with or without cytidine or uridine (both 25-400 microM), and with or without choline (20-40 microM), and measured the spontaneous and potassium-evoked release of acetylcholine.
Striatal slices stimulated for 2 h released 2650+/-365 pmol of acetylcholine per mg protein when incubated without choline, or 4600+/-450 pmol/mg protein acetylcholine when incubated with choline (20 microM). Adding cytidine or uridine (both 25-400 microM) to the media failed to affect acetylcholine release whether or not choline was also added, even though the pyrimidines (400 microM) did enhance choline;s utilization to form CDP-choline by 89 or 61%, respectively. The pyrimidines also had no effect on acetylcholine release from hippocampal and cortical slices. Cytidine or uridine also failed to affect acetylcholine levels in striatal slices, nor choline transport into striatal synaptosomes.
These data show that cytidine and uridine can stimulate brain phosphatide synthesis without diminishing acetylcholine synthesis or release.
能增加脑片乙酰胆碱释放的治疗方法会降低脑片中磷脂酰胆碱的合成及其水平。我们研究了向脑片培养基中添加胞苷或尿苷是否也会降低乙酰胆碱水平和释放，添加胞苷或尿苷会增加胆碱用于形成磷脂的利用率。
我们将大鼠脑片分别在添加或不添加胞苷或尿苷（均为25 - 400微摩尔）以及添加或不添加胆碱（20 - 40微摩尔）的情况下进行孵育，然后测量乙酰胆碱的自发释放和钾诱发释放。
在不添加胆碱的情况下孵育2小时的纹状体脑片每毫克蛋白质释放2650±365皮摩尔乙酰胆碱，而在添加胆碱（20微摩尔）的情况下孵育则释放4600±450皮摩尔/毫克蛋白质乙酰胆碱。向培养基中添加胞苷或尿苷（均为25 - 400微摩尔），无论是否添加胆碱，均未影响乙酰胆碱的释放，尽管嘧啶（400微摩尔）分别使胆碱用于形成CDP - 胆碱的利用率提高了89%或61%。嘧啶对海马和皮层脑片的乙酰胆碱释放也没有影响。胞苷或尿苷也未影响纹状体脑片中的乙酰胆碱水平，也未影响胆碱向纹状体突触小体的转运。
这些数据表明，胞苷和尿苷可以刺激脑磷脂合成，而不会减少乙酰胆碱的合成或释放。
