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

各种内源性物质，包括肾中表达的ABC和SLC转运蛋白底物，排泄到尿中。在这项研究中，我们每隔一段时间收集一名年轻健康女性分娩前后的晨尿（共15份样本）和白尿（共4天，18份样本），以检测疏水尿液成分（甲醇提取物）与p -糖蛋白（P-gp）和多药耐药相关蛋白（MRPs）之间可能的相互作用。产前收集的12份尿样中有4份和产后收集的3份尿样中有1份明显抑制P-gp功能。尿提取物对P-gp的抑制作用与分娩时间没有关系。白天的尿样显示出明显的昼夜节律，其中四个尿样中有三个在早上表现出比其他尿样更大的P-gp抑制能力。在Caco-2细胞中未检测到尿提取物与MRPs的相互作用。综上所述，尿中含有多种内源性P-gp底物/抑制剂，且内源性P-gp抑制剂浓度在晨尿中较高。妊娠和哺乳期不影响尿提取物对P-gp的抑制作用。

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.