Transport and Binding of Chloroguanide-Triazine by Rat Liver Slices 1

Abstract

Summary

When rat liver slices were incubated aerobically at 37° with 3.5×10^-7 M chloroguanide-triazine (CGT), the compound readily entered the tissue against an apparent concentration gradient. After 2 hr, the slice/medium concentration ratio was 9, and after 4 hr about 12. Uptake of CGT into slices occurred by a process that became saturated at high concentrations of the drug. Uptake was diminished by anaerobic conditions and by metabolic inhibitors such as iodoacetate and 2, 4-dinitrophenol. Uptake was also inhibited by certain tertiary and quaternary amine compounds, which pre-iodoacetate and 2, 4-dinitrophenol. Uptake process. These results suggested that CGT is taken up by liver slices at least in part by an active transport process that is closely related to the process which secretes CGT and certain other tertiary and quaternary amines into bile in vivo. CGT also entered liver slices by a process of diffusion. The compound was highly bound to homogenates of rat liver, suggesting that part of the accumulation seen in liver slices results from binding to tissue components.