Life Sciences Commons^™

Understanding the molecular basis for chloroquine resistance in Plasmodium falciparum will provide important support for the development of new therapies and prophylactic measures against malaria. Complementary genetic and biochemical investigations should discriminate among current theories and pinpoint the functional determinants of resistance. With this in mind Sanchez et al. 1998 have proposed that the P. falciparum cg2 gene, linked by Su et al. 1997 to chloroquine resistance, may encode a sodium/hydrogen exchanger (NHE) responsible for drug transport. Here, we present evidence against this proposal. Detailed reanalysis of the CG2 sequence fails to support the claims for significant similarity to functional …

Despite their similarity in structure, pyrrolizidine alkaloids (PAs) vary in their LD50s and in the organs in which toxicity is expressed. We have examined whether there are differences in the metabolism of certain PAs that are associated with these quantitative and qualitative differences in toxicity. Isolated rat livers were perfused with one of four PAs (seneciphylline, retrorsine, monocrotaline, and trichodesmine) at 0.5 mM for 1 hr, and the pyrrolic metabolites determined that were released into perfusate and bile or bound in the liver. The proportion of the PA removed by the liver varied from 93% for retrorsine to 55% for …