Tobacco budworm P-glycoprotein: biochemical characterization and its involvement in pesticide resistance.
Since pesticides have been shown to interact with P-glycoprotein (P-gp), the purpose of this study was to examine the possible role of P-gp in pesticide resistance in the tobacco budworm (Heliothis virescens). Using three P-gp antibodies, P-gp expression in various resistant populations of tobacco budworms was found to be 2-6-times that of the susceptible larvae. Tobacco budworm P-gp was glycosylated and localized primarily in the cuticle and fat body with little expression in the mid gut. To determine the role of P-gp in pesticide resistance, resistant tobacco budworm larvae were treated with a P-gp inhibitor, quinidine, and challenged with various doses of thiodicarb. Inhibition of P-gp decreased the LD50 for thiodicarb by a factor of 12.5. Quinidine treatment did not result in a significant inhibition of the P-450 system nor did it alter the feeding of the larvae, suggesting the potential involvement of P-gp in pesticide resistance. An age-dependent increase in P-gp expression was detected in resistant larvae as compared to control, susceptible larvae. This correlates with the reported age-dependent increase in resistance and is further evidence supporting the role of P-gp in the development of pesticide resistance.
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710, USA.
C L
CL
Lanning
R L
RL
Fine
J J
JJ
Corcoran
H M
HM
Ayad
R L
RL
Rose
M B
MB
Abou-Donia
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D000840:Anisoles / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D018432:Drug Resistance, Multiple / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006031:Glycosylation; D007306:Insecticides / Q000633:toxicity*; D007814:Larva / Q000737:chemistry / Q000187:drug effects; D007915:Lepidoptera / Q000737:chemistry / Q000187:drug effects* / Q000254:growth & development; D007928:Lethal Dose 50; D008970:Molecular Weight; D010882:Piperonyl Butoxide / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology; D013859:Thiocarbamates / Q000633:toxicity*; D014747:Vinblastine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000840:Anisoles; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007306:Insecticides; D013859:Thiocarbamates; D014747:Vinblastine; D003577:Cytochrome P-450 Enzyme System; D011803:Quinine; C005306:4-nitroanisole; D011802:Quinidine; C027971:thiodicarb; D010882:Piperonyl Butoxide