Uptake of pentamidine in Trypanosoma brucei brucei is mediated by three distinct transporters: implications for cross-resistance with arsenicals.

摘要: The trypanocidal action of pentamidine is dependent on the rapid, selective accumulation this drug by parasite. We have investigated transport bloodstream and procyclic life cycle stages Trypanosoma brucei brucei. In forms, 50 to 70% [(3)H]pentamidine was transported an adenosine-sensitive transporter (ASPT1) that displayed a K(m) value 0.26 +/- 0.03 microM K(i) values 0.45 0.04 2.5 0.8 for adenine berenil, respectively. These are very similar those inhibition [(3)H]adenosine uptake P2 adenosine/adenine transporter, suggesting ASPT1 may be identical. remaining 30 50% mediated low-capacity high-affinity (HAPT1) high-capacity low-affinity (LAPT1), with 36 6 nM 56 8 microM, HAPT1 inhibited propamidine but only low affinity berenil stilbamidine, whereas LAPT1 not any these diamidines. Neither melarsen oxide. procyclics, HAPT1-analog (procyclic transporter; PPT1) characterized, no could detected. Treatment ionophores revealed PPT1 proton/pentamidine cotransporter.