Pesticides have been shown to interact with the multidrug resistance protein associated with cancer chemotherapy, P-glycoprotein (P-gp). P-gp, therefore, has also been implicated in the development of pesticide resistance. The purpose of this study was to characterize the effect P-gp has on the accumulation of the carbamate pesticide, thiodicarb. For these studies, resistant tobacco budworm larvae, expressing four times the P-gp as susceptible larvae, were pretreated with the P-gp inhibitor, quinidine, and challenged topically with thiodicarb. Quinidine enhanced thiodicarb toxicity in a dose-dependent manner, with mortality in the presence of P-gp inhibition increased up to 33%. Quinidine treatment increased [14C]thiodicarb accumulation 2- to 3-fold as compared to thiodicarb treatment alone. This study suggests that P-gp contributes to quinidine synergism of thiodicarb toxicity and suggests that P-gp may be involved in cuticular resistance to pesticides.
