ALTERATIONS IN DRUG TRANSPORT IN RESISTANT TRYPANOSOMA-CONGOLENSE

The transport of isometamidium chloride (Samorin ) in Trypanosoma cong olense which were either sensitive or resistant to this widely used tr ypanocide was studied in vitro. Significantly lower amounts of drug we re accumulated over time by resistant than by sensitive trypanosomes. While no direct evidence could be obtained, indirect observations impl ied the involvement of an increased efflux of drug from the resistant trypanosomes. In both the resistant and sensitive parasites, drug tran sport was found to be mediated by an energy-dependent, specific proces s, presumably receptor-mediated. However, the specificity of the putat ive receptors was altered in the drug-resistant parasites. It is propo sed that an alteration or replacement of a specific receptor in isomet amidium chloride-resistant T. congolense results in an increased efflu x of the drug and that this increased efflux at least partially mediat es the reduction in sensitivity to the compound.