Sensitivity of Leishmania spp. to Glibenclamide and 4-Aminopiridine: A Tool for the Study of Drug Resistance Development

Memórias do Instituto Oswaldo Cruz

Alicia Ponte-sucre¹  Yelitza Campos¹  Jorge Vázquez¹  Heidrun Moll¹  Alexis Mendoza-león¹ 

关键词: Leishmania;    chemotherapy;    glibenclamide;    4-aminopyridine;    drug resistance;    P-glycoprotein;   

DOI  :  10.1590/S0074-02761997000500007

来源: SciELO

【 摘 要 】

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)

【 授权许可】

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