Direct evidence for peptide transporter (PepT1)-mediated uptake of a nonpeptide prodrug, valacyclovir
Direct evidence for peptide transporter (PepT1)-mediated uptake of a nonpeptide prodrug, valacyclovir
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DOI：
10.1006/bbrc.1998.9298
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发表时间：
1998-09-18
影响因子：
3.1
通讯作者：
Sinko, PJ
中科院分区：
文献类型：
--
作者：
Balimane, PV;Tamai, I;Sinko, PJ
非洲爪蟾卵母细胞被用作基因表达系统，以表征载体介导的无环核苷阿昔洛韦（acv）的L-缬氨酸酯前药伐昔洛韦（vacv）的转运。与注射水的卵母细胞相比，注射人肠肽转运蛋白（hPepT 1）cRNA的非洲爪蟾卵母细胞对[H-3]vacv的摄取显著增加，表明vacv被hPepT 1易位。发现Vacv摄取是浓度依赖性的、可饱和的（Km = 5.94 +/- 1.91 mM和J（max）= 1.68 +/- 0.25 nmol/hr/卵母细胞）、pH依赖性的，并且被hPepT 1的各种已知底物抑制，但不被acv、缬氨酸或五甘氨酸抑制。Vacv还以浓度依赖性方式抑制C-14-甘氨酰肌氨酸（hPepT 1的已知底物）的摄取（Ki = 4.08 +/- 1.02 mM）。这些结果表明，人肠肽转运蛋白hPepT 1具有广泛的特异性，因为它识别作为底物的vacv，即使它缺乏典型的肽键。(C)北京：科学出版社.
Xenopus laevis oocytes were used as a gene expression system to characterize the carrier-mediated transport of valacyclovir (vacv), the L-valine ester prodrug of the acyclic nucleoside acyclovir (acv). A significant increase in the uptake of [H-3]vacv by Xenopus laevis oocytes injected with human intestinal peptide transporter (hPepT1) cRNA compared to the uptake by water injected oocytes indicated that vacv was translocated by hPepT1. Vacv uptake was found to be concentration dependent, saturable (K-m = 5.94 +/- 1.91 mM and J(max) = 1.68 +/- 0.25 nmoles/hr/oocyte), pH dependent, and inhibited by various known substrates of hPepT1 but not by acv, valine or pentaglycine. Vacv also inhibited the uptake of C-14-glycylsarcosine, a known substrate of hPepT1, in a concentration-dependent manner (K-i = 4.08 +/- 1.02 mM). These results demonstrate that human intestinal peptide transporter hPepT1 has broad specificity since it recognizes vacv as a substrate even though it lacks a typical peptide bond. (C) 1998 Academic Press.