首页> 美国卫生研究院文献>other >Influence of Peptide Transporter 2 (PEPT2) on the Distribution of Cefadroxil in Mouse Brain: A Microdialysis Study
【2h】

Influence of Peptide Transporter 2 (PEPT2) on the Distribution of Cefadroxil in Mouse Brain: A Microdialysis Study

机译:肽转运蛋白2(PEPT2)对头孢羟氨苄在小鼠大脑中的分布的影响:微透析研究

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。
获取外文期刊封面目录资料

摘要

Peptide transporter 2 (PEPT2) is a high-affinity low-capacity transporter belonging to the proton-coupled oligopeptide transporter family. Although many aspects of PEPT2 structure-function are known, including its localization in choroid plexus and neurons, its regional activity in brain, especially extracellular fluid (ECF), is uncertain. In this study, the pharmacokinetics and regional brain distribution of cefadroxil, a β-lactam antibiotic and PEPT2 substrate, were investigated in wildtype and Pept2 null mice using in vivo intracerebral microdialysis. Cefadroxil was infused intravenously over 4 hours at 0.15 mg/min/kg, and samples obtained from plasma, brain ECF, cerebrospinal fluid (CSF) and brain tissue. A permeability-surface area experiment was also performed in which 0.15 mg/min/kg cefadroxil was infused intravenously for 10 min, and samples obtained from plasma and brain tissues. Our results showed that PEPT2 ablation significantly increased the brain ECF and CSF levels of cefadroxil (2- to 2.5-fold). In contrast, there were no significant differences between wildtype and Pept2 null mice in the amount of cefadroxil in brain cells. The unbound volume of distribution of cefadroxil in brain was 60% lower in Pept2 null mice indicating an uptake function for PEPT2 in brain cells. Finally, PEPT2 did not affect the influx clearance of cefadroxil, thereby, ruling out differences between the two genotypes in drug entry across the blood-brain barriers. These findings demonstrate, for the first time, the impact of PEPT2 on brain ECF as well as the known role of PEPT2 in removing peptide-like drugs, such as cefadroxil, from the CSF to blood.
机译:肽转运蛋白2(PEPT2)是一种高亲和力的低容量转运蛋白,属于质子偶联的寡肽转运蛋白家族。尽管PEPT2结构功能的许多方面是已知的,包括其在脉络丛和神经元中的定位,但其在大脑(尤其是细胞外液(ECF))中的区域活性尚不确定。在这项研究中,使用体内脑内微透析技术,在野生型和Pept2无效的小鼠中研究了头孢羟氨苄,一种β-内酰胺类抗生素和PEPT2底物的药代动力学和脑区域分布。以0.15 mg / min / kg的剂量在4个小时内静脉内注射头孢氨苄,并从血浆,脑ECF,脑脊液(CSF)和脑组织中获取样品。还进行了渗透性表面积实验,其中静脉内注入0.15 mg / min / kg头孢氨苄10分钟,并从血浆和脑组织中获取样品。我们的研究结果表明,PEPT2消融可显着提高头孢羟氨苄的脑ECF和CSF水平(2-至2.5倍)。相比之下,野生型和Pept2无效小鼠之间脑细胞中头孢羟氨苄的含量没有显着差异。在Pept2缺失的小鼠中,头孢羟氨苄在大脑中的未分配分布体积降低了60%,表明脑细胞中PEPT2的摄取功能。最后,PEPT2不会影响头孢氨苄的入流清除率,从而排除了跨血脑屏障药物进入的两种基因型之间的差异。这些发现首次证明了PEPT2对大脑ECF的影响,以及PEPT2在从CSF到血液中清除肽样药物(例如头孢阿地尔)的已知作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号