Putative P-glycoprotein expression in arsenite-resistant Leishmania donovani down-regulated by verapamil.

Western immunoblots of whole cell lysate and crude membrane extract of an in vitro selected sodium m-arsenite-resistant L. donovani strain revealed a 230-kDa protein identified by an anti-P-glycoprotein (Pgp) antibody. Immunofluorescence microscopy, using the same antibody, detected putative Pgp on resistant parasites. Overexpression of the putative Pgp was down-regulated by verapamil. These results provided, possibly, the first evidence that (i) overexpression of Pgp-like protein occurs in arsenite-resistant Leishmania that are cross-resistant to structurally and functionally unrelated drugs and (ii) verapamil regulates drug sensitivity possibly by down-regulating Pgp expression in the arsenite-resistant Leishmania.