We have demonstrated that Leishmania spp. grown as promastigotes, are
sensitive to the K^+ channel inhibitors 4-aminopyridine and glibenclamide.
Their host cells, the macrophages, are not affected by similar
concentrations of the drugs. We have also initiated the molecular
characterization of the mechanisms involved in the development of drug
resistance to glibenclamide by the parasite. Therefore, we have selected
experimentally and begun to characterize the Venezuelan Leishmania
(Leishmania) strain, NR resistant to glibenclamide [NR(Gr)]. The analysis
of genomic DNA evidenced the existence of a fragment which apparently is
amplified in NR(Gr). The fragment recognized by the pgpA probe, related to
the Leishmania P-glycoprotein family and which was originally isolated from
L. tarentolae, showed a size polymorfism between the sensitive and the
resistant strain. These results suggest that the development of resistance
to glibenclamide in the strain NR(Gr) might be associated with the
amplification of the ltpgpA or related gene(s).
