Klein J, Köppen A, Löffelholz K, Schmitthenner J
Department of Pharmacology, University of Mainz, F.R.G.
J Neurochem. 1992 Mar;58(3):870-6. doi: 10.1111/j.1471-4159.1992.tb09337.x.
The present study is concerned with the uptake and metabolism of choline by the rat brain. Intraperitoneal administration of choline chloride (4-60 mg/kg) caused a dose-dependent elevation of the plasma choline concentration from 11.8 to up to 165.2 microM within 10 min and the reversal of the negative arteriovenous difference (AVD) of choline across the brain to positive values at plasma choline levels of greater than 23 microM. Net choline release and uptake were linearly dependent on the plasma choline level in the physiological range of 10-50 microM, whereas the CSF choline level was significantly increased only at plasma choline levels of greater than 50 microM. The bolus injection of 60 mg/kg of [3H]choline chloride caused the net uptake of greater than 500 nmol/g of choline by the brain as calculated from the AVD, which was reflected in a minor increase of free choline level and a long-lasting increase of brain phosphorylcholine content, which paralleled the uptake curve. Loss of label from phosphorylcholine 30 min to 24 h after choline administration was accompanied by an increase of label in phosphatidylcholine, an indication of a delayed transfer of newly taken-up choline into membrane choline pools. In conclusion, homeostasis of brain choline is maintained by a complex system that interrelates choline net movements into and out of the brain and choline incorporation into and release from phospholipids.
本研究关注大鼠脑对胆碱的摄取和代谢。腹腔注射氯化胆碱(4 - 60毫克/千克)导致血浆胆碱浓度在10分钟内呈剂量依赖性升高,从11.8微摩尔/升升至高达165.2微摩尔/升,并且当血浆胆碱水平大于23微摩尔/升时,脑内胆碱的负动静脉差值(AVD)逆转至正值。在10 - 50微摩尔/升的生理范围内,胆碱的净释放和摄取与血浆胆碱水平呈线性相关,而只有当血浆胆碱水平大于50微摩尔/升时,脑脊液胆碱水平才会显著升高。静脉注射60毫克/千克的[3H]氯化胆碱后,根据AVD计算,脑对胆碱的净摄取量大于500纳摩尔/克,这表现为游离胆碱水平略有升高以及脑磷酸胆碱含量持续增加,且与摄取曲线平行。胆碱给药后30分钟至24小时,磷酸胆碱中的标记物丢失伴随着磷脂酰胆碱中标记物的增加,这表明新摄取的胆碱向膜胆碱池的转移延迟。总之,脑胆碱的稳态由一个复杂的系统维持,该系统将胆碱进出脑的净移动与胆碱掺入磷脂和从磷脂中释放联系起来。