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Título : Sensitivity of Leishmania spp. to glibenclamide and 4-aminopyridine: a tool for the study of drug resistance development.
Autor : Ponte-Sucre, Alicia
Campos, Yelitza
Vazquez, Jorge
Moll, Heidrun
Mendoza-León, Alexis
Palabras clave : Drug resistance
Ion channel blockers
Leishmania
Fecha de publicación : 28-Aug-2012
Citación : Memórias do Instituto Oswaldo Cruz;92: 601-606, 1997.
Resumen : 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).
URI : http://saber.ucv.ve/123456789/1716
ISSN : 0074-0276
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