Sakurai E, Monura A, Yamakami J, Hikichi N
Department of Pharmaceutics I, Tohoku College of Pharmacy, Sendai, Japan.
J Pharm Pharmacol. 1996 Sep;48(9):911-3. doi: 10.1111/j.2042-7158.1996.tb06000.x.
The blood concentrations of 5-hydroxytryptamine (5-HT) and its metabolites, 5-hydroxyindoleacetic acid (5-HIAA) and N-acetyl 5-HT were assayed by in-vivo microdialysis and a highly sensitive HPLC procedure that was originally developed to analyse CNS mediators. We investigated the effects of histamine-receptor antagonists on 5-HT metabolism and its release into the blood of rats. The mean basal levels of 5-HT, 5-HIAA and N-acetyl 5-HT in the blood measured by in-vivo microdialysis were 77.2 +/- 9.4, 20.3 +/- 1.5 and 1.89 +/- 0.15 pmol mL-1, respectively. These levels were not significantly affected by an intraperitoneal injection of saline, and remained at constant levels for at least 8 h after administration of saline. After an intraperitoneal injection of 5-HT hydrochloride (0.5 mg kg-1), 5-HT was soon detected in the blood of the jugular vein. 5-HIAA also quickly appeared in the blood and declined monoexponentially from 60 min after injection. In contrast, N-acetyl 5-HT slowly appeared in the blood and it reached a maximal level at 270 min. The 5-HT and N-acetyl 5-HT levels in dialysates from rat jugular vein were significantly increased by intraperitoneal pyrilamine (2.0 mg kg-1), (+)-chlorpheniramine (2.0 mg kg-1) and cimetidine (20.0 mg kg-1). However, there was no increase in the 5-HIAA concentration after an intraperitoneal injection of these histamine-receptor antagonists, demonstrating that the 5-HT released from various cells containing 5-HT was predominantly metabolized to N-acetyl 5-HT by N-acetyltransferase. Moreover, thioperamide did not affect the basal levels of 5-HT, 5-HIAA or N-acetyl 5-HT. Because the recovered 5-HT, 5-HIAA and N-acetyl 5-HT in the dialysate is directly proportional to the free fraction in the blood, in-vivo microdialysis is a reliable method of examining 5-HT metabolism and its release into the blood.
采用体内微透析技术和最初用于分析中枢神经系统介质的高灵敏度高效液相色谱法（HPLC）测定了5-羟色胺（5-HT）及其代谢产物5-羟吲哚乙酸（5-HIAA）和N-乙酰5-HT的血药浓度。我们研究了组胺受体拮抗剂对5-HT代谢及其释放到大鼠血液中的影响。通过体内微透析测定的血液中5-HT、5-HIAA和N-乙酰5-HT的平均基础水平分别为77.2±9.4、20.3±1.5和1.89±0.15 pmol/mL-1。腹腔注射生理盐水对这些水平没有显著影响，注射生理盐水后至少8小时内保持恒定水平。腹腔注射盐酸5-HT（0.5 mg/kg-1）后，很快在颈静脉血液中检测到5-HT。5-HIAA也迅速出现在血液中，并在注射后60分钟开始呈单指数下降。相比之下，N-乙酰5-HT在血液中出现较慢，在270分钟时达到最高水平。腹腔注射吡苄明（2.0 mg/kg-1）、（+）-氯苯那敏（2.0 mg/kg-1）和西咪替丁（20.0 mg/kg-1）可显著提高大鼠颈静脉透析液中5-HT和N-乙酰5-HT的水平。然而，腹腔注射这些组胺受体拮抗剂后5-HIAA浓度没有增加，这表明从各种含5-HT的细胞释放的5-HT主要被N-乙酰转移酶代谢为N-乙酰5-HT。此外，硫代哌啶对5-HT、5-HIAA或N-乙酰5-HT的基础水平没有影响。由于透析液中回收的5-HT、5-HIAA和N-乙酰5-HT与血液中的游离部分成正比，因此体内微透析是检测5-HT代谢及其释放到血液中的可靠方法。
