Lockman Paul R, Gaasch Julie, McAfee Ghia, Abbruscato Thomas J, Van der Schyf Cornelis J, Allen David D
Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, 79106-1712, USA.
Neurochem Res. 2006 Apr;31(4):503-8. doi: 10.1007/s11064-006-9047-5. Epub 2006 May 9.
Acute and chronic nicotine exposure in rats is associated with an increase in brain acetylcholine (ACh) transmission. The acquisition of choline for neuronal ACh synthesis occurs primarily via two pathways; first, free choline is transported from the blood across the blood-brain barrier (BBB) and/or second, from synaptic choline generated by either hydrolysis of non-bound ACh or membrane phosphatidylcholine catabolism. To determine if nicotine-induced cholinergic demand is associated with increased choline transport rates into brain, we measured BBB choline transport in naïve and S-(-) nicotine exposed rats (acute and chronic, 4.5 mg/kg/d for 1, 14, 21 and 28 d; osmotic minipumps) using the in situ rat brain perfusion technique. No significant changes in choline uptake after acute or chronic nicotine exposure were observed in whole brain or cortex. Of considerable interest was a significant decrease in regional brain choline uptake measured in the hippocampus after chronic nicotine exposure (28 d). Our data suggest that the increased ACh transmission observed after nicotine exposure does not correlate with increased blood-to-brain transfer of choline. Considering these data and previous literature reports, we propose that the additional free choline required under conditions of nicotine exposure (for ACh synthesis) is primarily recruited from membrane phospholipid metabolism.
大鼠急性和慢性尼古丁暴露与脑内乙酰胆碱（ACh）传递增加有关。神经元合成ACh所需胆碱的获取主要通过两条途径；第一，游离胆碱从血液穿过血脑屏障（BBB）转运进来，和/或第二，来自未结合ACh水解或膜磷脂酰胆碱分解代谢产生的突触胆碱。为了确定尼古丁诱导的胆碱能需求是否与脑内胆碱转运速率增加有关，我们使用原位大鼠脑灌注技术，测量了未接触过尼古丁和S-（-）尼古丁暴露大鼠（急性和慢性，4.5mg/kg/d，持续1、14、21和28天；渗透微型泵）的BBB胆碱转运。在全脑或皮质中，急性或慢性尼古丁暴露后胆碱摄取均未观察到显著变化。值得关注的是，慢性尼古丁暴露（28天）后，海马区测量的脑区胆碱摄取显著下降。我们的数据表明，尼古丁暴露后观察到的ACh传递增加与胆碱从血液到脑的转运增加无关。考虑到这些数据和以前的文献报道，我们提出，尼古丁暴露条件下（用于ACh合成）所需的额外游离胆碱主要来自膜磷脂代谢。
