药物与肠道肽转运蛋白PEPT1的相互作用及影响因素

Interactions of intestinal H^+/oligopeptide cotransporter PEPT1 with drugs and regulation by affecting factors

H+协同转运载体PEPT1主要存在于小肠上皮细胞的刷状缘膜上,肠道PEPT1对于消化道中蛋白质的降解产物二肽、三肽具有转运吸收的功能,另外肽类似药物如β-内酰胺类抗生素、血管紧张素转化酶抑制剂、非肽药物伐昔洛韦等也经此载体转运吸收。肠道PEPT1对于维持机体的内环境稳定以及药物的胃肠道吸收发挥重要作用。随着对PEPT1基因序列、蛋白结构、功能活性等方面研究的逐渐深入,对于调控PEPT1在膜上表达、影响其功能活性以及与底物亲和力的因素及相关的作用机制有了一定的了解,加之PEPT1广泛的底物专属性,使其成为新药开发中重要的药物传递的靶蛋白。了解药物与肠道肽转运蛋白PEPT1的相互作用及其影响因素,对于了解药物-药物相互作用,提高药物口服吸收的生物利用度,研究抗肿瘤药物的靶向治疗以及个体化给药等方面具有十分重要的意义。

H^＋/oligopeptide cotransporter PEPT1 mainly located at the brush border membrane of intestinal epithelium cell. transports dipeptide/tripeptide which is the degradation products of protein in digestive tract. Peptide-like drugs such as β-lactam antibiotics, angiotensin-converting enzyme inhibitor （ACEI） and non-peptide drugs valaciclovir also can be transported and uptaked by PEPT1. PEPT1 is important for maintaining the homeostasis and the absorption of drugs in gastrointestinal tract. With the further research of PEPT1 gene, protein structure, and functional activity, we have known the factors about regulation of PEPTI expression in membrane,their functional activities and substrate affinities. Some associated mechanism of regulation have been studied. As the wide substrate specificities of PEPT1, it becomes the target molecular on drug development and implication for drug delivery. Studies about interactions of PEPT1 with drugs are important for knowing the interactions of drugs, evaluating bioavailability of drug by intestinal absorption, researching the target treatment in anti-tumor drugs and individualization administration.