Sinefungin shares AdoMet-uptake system to enter Leishmania donovani promastigotes.
The involvement of a carrier for sinefungin (SF) uptake in Leishmania donovani promastigotes is indicated by saturation kinetics, competition studies and SF accumulation against a 270-fold concentration gradient across the cell membrane. Whether SF uptake occurs via nucleoside- or AdoMet-carrier systems was investigated by competition experiments and comparison of the uptake of various molecules in wild-type and SF-resistant cells. Results show that SF did not inhibit purine or pyrimidine uptake whereas it competitively inhibited AdoMet uptake. Furthermore, the uptake of nucleosides in SF-resistant cells is similar to that in wild-type cells, whereas uptake of SF and AdoMet is lower.
Phelouzat
M A
MA
Institut de Chimie des Substances Naturelles, C.N.R.S., Gif-sur Yvette, France.
Basselin
M
M
Lawrence
F
F
Robert-Gero
M
M
D000241:Adenosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000818:Animals; D004351:Drug Resistance; D007700:Kinetics; D007893:Leishmania donovani / Q000254:growth & development / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000493:pharmacokinetics*
D026901:Membrane Transport Proteins; D015800:Protozoan Proteins; D012436:S-Adenosylmethionine; D000241:Adenosine; C006235:sinefungin