P-glycoprotein involvement in cuticular penetration of [C-14]thiodicarb in resistant tobacco budworms

P-glycoprotein involvement in cuticular penetration of [C-14]thiodicarb in resistant tobacco budworms
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DOI:
10.1016/0378-4274(96)03654-5
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发表时间:
1996-06-01
期刊:
影响因子:
3.5
通讯作者:
AbouDonia, MB
AbouDonia, MB
中科院分区:
医学3区
文献类型:
--
作者:
Lanning, CL;Ayad, HM;AbouDonia, MB

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农药已被证明与癌症化疗相关的多药耐药蛋白P-糖蛋白(P-gp)相互作用[1,2]。因此,P-gp也与杀虫剂抗性的发展有关[3]。本研究的目的是表征P-gp对氨基甲酸酯农药硫双威积累的影响。在这些研究中,抗性烟青虫幼虫,表达四倍的P-gp敏感幼虫,预处理的P-gp抑制剂,奎尼丁,局部与硫双威的挑战。奎尼丁以剂量依赖性方式增强硫双威毒性,在P-gp抑制剂存在下死亡率增加至33%。与单独硫双威处理相比,奎尼丁处理使[C-14]硫双威积累增加2至3倍。这项研究表明,P-gp有助于奎尼丁协同硫双威的毒性,并建议P-gp可能参与表皮抗药性的农药。
Pesticides have been shown to interact with the multidrug resistance protein associated with cancer chemotherapy, P-glycoprotein (P-gp) [1,2]. P-gp, therefore, has also been implicated in the development of pesticide resistance [3]. 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 [C-14]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.