P-glycoprotein involvement in cuticular penetration of [14C]thiodicarb in resistant tobacco budworms.
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.
Lanning
C L
CL
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Ayad
H M
HM
Abou-Donia
M B
MB
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D000818:Animals; D001681:Biological Assay; D002855:Chromatography, Thin Layer; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple / Q000502:physiology; D004357:Drug Synergism; D015151:Immunoblotting; D007305:Insecticide Resistance / Q000502:physiology*; D007306:Insecticides / Q000378:metabolism* / Q000633:toxicity; D007553:Isotope Labeling; D007814:Larva / Q000187:drug effects / Q000378:metabolism; D009036:Moths / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000378:metabolism / Q000494:pharmacology; D011802:Quinidine / Q000378:metabolism / Q000494:pharmacology; D013859:Thiocarbamates / Q000378:metabolism* / Q000633:toxicity
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007306:Insecticides; D011500:Protein Synthesis Inhibitors; D013859:Thiocarbamates; D011802:Quinidine; C027971:thiodicarb