Nakatani Yasushi, Sato-Suzuki Ikuko, Tsujino Naohisa, Nakasato Akane, Seki Yoshinari, Fumoto Masaki, Arita Hideho
Department of Physiology, Toho University School of Medicine, 5-21-16, Omori-nishi, Ota-ku, Tokyo 143-8540, Japan.
Eur J Neurosci. 2008 May;27(9):2466-72. doi: 10.1111/j.1460-9568.2008.06201.x.
The present study re-evaluated an existing notion that serotonin (5-hydroxytryptamine; 5-HT) could not cross the brain to the circulating blood via the blood-brain barrier (BBB). To elevate brain 5-HT alone, 5-hydroxytryptophan (5-HTP; 30-75 mg/kg) was administrated intravenously to anaesthetized rats that had undergone gastrointestinal and kidney resections along with liver inactivation (organs contributing to increasing blood 5-HT after 5-HTP administration). A microdialysis method and HPLC system were used to determine the brain 5-HT levels in samples collected from the frontal cortex. Blood 5-HT levels were determined from whole blood, not platelet-poor plasma, collected from the central vein. We found that blood 5-HT levels showed a significant augmentation whenever brain 5-HT levels were significantly elevated after the administration of 5-HTP in those rats with the abdominal surgical procedures. This elevation was abolished after pretreatment with a selective serotonin reuptake inhibitor (fluoxetine; 10 mg/kg i.v.), although brain 5-HT levels remained augmented. These results indicate that augmented brain 5-HT can cross the BBB through the 5-HT transporter from the brain to the circulating blood.
本研究重新评估了一种现有的观念，即血清素（5-羟色胺；5-HT）无法通过血脑屏障（BBB）从大脑进入循环血液。为了单独提高大脑中的5-HT水平，对已进行胃肠和肾脏切除以及肝脏灭活（这些器官在给予5-HTP后会导致血液中5-HT升高）的麻醉大鼠静脉注射5-羟色氨酸（5-HTP；30 - 75 mg/kg）。采用微透析法和高效液相色谱系统测定从额叶皮质采集的样本中的大脑5-HT水平。从中央静脉采集的全血（而非血小板缺乏血浆）中测定血液中的5-HT水平。我们发现，在那些接受腹部手术的大鼠中，给予5-HTP后，每当大脑5-HT水平显著升高时，血液中的5-HT水平就会显著升高。在用选择性5-羟色胺再摄取抑制剂（氟西汀；10 mg/kg静脉注射）预处理后，这种升高被消除，尽管大脑5-HT水平仍保持升高。这些结果表明，升高的大脑5-HT可以通过5-羟色胺转运体从大脑穿过血脑屏障进入循环血液。
