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 [3H]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 14C-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.
|Original language||English (US)|
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Sep 18 1998|
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology