Martel C L, Mackic J B, Adams J D, McComb J G, Weiss M H, Zlokovic B V
Department of Neurosurgery, University of Southern California School of Medicine, Los Angeles 90033, USA.
Pharm Res. 1996 Feb;13(2):290-5. doi: 10.1023/a:1016007601794.
Transport of dopamine (DA) across the blood-brain barrier (BBB) was examined in guinea pigs.
In situ brain perfusion (1-10 min), capillary depletion, and high pressure liquid chromatography (HPLC) were used.
There was a saturable DA influx into the brain with a KM of 389 +/- 55 nM, and a VMAX of 1.95 +/- 0.25 pmol/min/g of brain. The diffusion constant, KD, was not significantly different from zero. About 0.5% of DA remained tightly bound to cerebral microvessels isolated from the perfused brain. DA influx into the brain was not altered by the monoamine oxidase-B (MAO-B) inhibitor pargyline (50 microM). HPLC analysis of perfused brain confirmed transport of intact DA, and no detectable increases in DA metabolites were observed. At perfusate concentrations of 500 nM, several dopaminergic receptor antagonists inhibited [3H]-DA (21 nM) influx; the percent inhibitions for the mixed D1 and D2 antagonists haloperidol and chlorpromazine, the D1 antagonist SCH-23390, and the D2 antagonist spiperone were 90%, 68%, 77%, and 50%, respectively. Brain perfusion with nicotine (500 nM) inhibited DA uptake by 86%. This nicotine effect was not altered by mecamylamine, but was partially prevented by the nicotinic receptor antagonist hexamethonium.
(a) A significant cerebrovascular permeability to intact DA is mediated by a MAO-B independent specific transport system at the BBB, (b) this system could be inhibited by D1 and D2 DA receptor antagonists, and (c) DA blood-to-brain transport was inhibited by nicotine.
在豚鼠中研究多巴胺（DA）穿过血脑屏障（BBB）的转运情况。
采用原位脑灌注（1 - 10分钟）、毛细血管耗竭法及高压液相色谱法（HPLC）。
DA向脑内的流入具有饱和性，米氏常数（KM）为389±55 nM，最大转运速率（VMAX）为1.95±0.25 pmol/分钟/克脑。扩散常数KD与零无显著差异。约0.5%的DA与从灌注脑分离的脑微血管紧密结合。单胺氧化酶 - B（MAO - B）抑制剂优降宁（50 microM）未改变DA向脑内的流入。对灌注脑的HPLC分析证实了完整DA的转运，且未观察到DA代谢产物有可检测到的增加。在灌注液浓度为500 nM时，几种多巴胺能受体拮抗剂抑制了[3H] - DA（21 nM）的流入；混合的D1和D2拮抗剂氟哌啶醇和氯丙嗪、D1拮抗剂SCH - 23390以及D2拮抗剂螺哌隆的抑制百分比分别为90%、68%、77%和50%。用尼古丁（500 nM）进行脑灌注使DA摄取减少了86%。这种尼古丁效应不受美加明影响，但烟碱受体拮抗剂六甲双铵可部分阻止该效应。
（a）BBB处完整DA的显著脑血管通透性由一个不依赖MAO - B的特异性转运系统介导；（b）该系统可被D1和D2 DA受体拮抗剂抑制；（c）尼古丁抑制了DA的血脑转运。
