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Interaction of hydrophobic components in female urine before and after childbirth with P-glycoprotein in vitro

女性分娩前后尿液中疏水性成分与体外P-糖蛋白的相互作用

基本信息

批准号：
22590162
负责人：
MORI Nobuhiro
金额：
$ 2.91万
依托单位：
Hiroshima International University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2012
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590162/
关键词：
医療薬剤学妊娠異物排出ポンプ P-gp Mrp2

项目摘要

Various endogenous substances including substrates for ABC and SLC transporters expressed in the kidney are excreted into urine. In this study, the first urine in the morning (total 15 samples) and urine in the daytime (total 4 days, 18 samples) were collected at intervals from a young healthy woman before and after childbirth, to examine possible interactions of hydrophobic urine components (methanol extracts) with P-glycoprotein (P-gp) and multidrug resistance-associated proteins (MRPs). Four urine samples out of 12 collected before childbirth and one sample out of three obtained after childbirth suppressed P-gp function significantly. No relationship was observed between the P-gp inhibitory potencies of urine extracts and the timing of childbirth. The daytime urine samples showed a clear circadian rhythm, in which three first urine samples in the morning out of four showed the greater P-gp inhibitory potencies than other samples. Interaction of urine extracts with MRPs was no detected in Caco-2 cells. In conclusion, urine contains various endogenous P-gp substrates/inhibitor(s), and the concentration of endogenous P-gp inhibitor(s) was higher in the first urine in the morning. Pregnancy and lactation did not affect the P-gp inhibitory potencies of urine extracts.

各种内源性物质（包括肾脏中表达的ABC和SLC转运蛋白的底物）经尿液排泄。在这项研究中，在早晨（共15个样本）和白天（共4天，18个样本）的第一次尿液中收集的时间间隔从一个年轻的健康妇女分娩前和分娩后，以检查疏水性尿液成分（甲醇提取物）与P-糖蛋白（P-gp）和多药耐药相关蛋白（MRP）的可能的相互作用。分娩前采集的12份尿样中有4份和分娩后采集的3份尿样中有1份明显抑制P-gp功能。未观察到尿提取物的P-gp抑制效力与分娩时间之间的关系。白天的尿液样本显示出明显的昼夜节律，其中四个早晨的第一次尿液样本中有三个样本显示出比其他样本更大的P-gp抑制效力。在Caco-2细胞中未检测到尿液提取物与MRPs的相互作用。总之，尿液中含有各种内源性P-gp底物/抑制剂，早晨第一次尿液中内源性P-gp抑制剂的浓度较高。妊娠和哺乳不影响尿提取物的P-gp抑制效力。