Chlorpyrifos oxon interacts with the mammalian multidrug resistance protein, P-glycoprotein
Abstract
Multidrug resistance (MDR) to chemically unrelated therapeutic anticancer agents in mammalian cells is mediated by the overexpression of an ATP-dependent 150- to 180-kD membrane glycoprotein P-glycoprotein (P-gp). Although the complete physiological role of P-gp is unknown, it is proposed to function in cellular detoxification of xenobiotics. In this study, we investigated whether the organophosphorus insecticide chlorpyrifos (O,O-diethyl O-3,5,6-trichloro-2-pyridinyl phosphorothioate) or its metabolites interact with P-gp. Immunohistochemical analysis of tissues from male Fischer 344 rats administered chlorpyrifos (7.6 mg/kg gavage) showed increased P-gp expression in the kidney, adrenal, liver, jejunum, and stomach (tissues associated with elimination of xenobiotics), compared to control tissues. The most prominent increase was detected in the large bile ducts of the liver and the proximal tubule region of the kidney. P-gp expression was increased throughout the adrenal medulla and cortex, while a moderate increase was detected in the epithelial layers of the stomach and jejunum. To examine further the interaction between chlorpyrifos and P-gp, we evaluated whether chlorpyrifos or its active metabolite, chlorpyrifos oxon, cou...Continue Reading
Citations
P-glycoprotein involvement in cuticular penetration of [14C]thiodicarb in resistant tobacco budworms
Intestinal permeability of chlorpyrifos using the single-pass intestinal perfusion method in the rat
Effect of organophosphate pesticide diazinon on expression and activity of intestinal P-glycoprotein
Interaction of insecticides with mammalian P-glycoprotein and their effect on its transport function
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