文献类型：期刊文献

英文题名：Insect nicotinic receptor interactions in vivo with neonicotinoid, organophosphorus, and methylcarbamate insecticides and a synergist

作者：Shao, Xusheng[1,3];Xia, Shanshan[3];Durkin, Kathleen A.[2];Casida, John E.[1]

机构：[1]Univ Calif Berkeley, Coll Chem, Environm Chem & Toxicol Lab, Dept Environm Sci Policy & Management, Berkeley, CA 94720 USA;[2]Univ Calif Berkeley, Coll Chem, Mol Graph & Computat Facil, Berkeley, CA 94720 USA;[3]E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China

年份：2013

卷号：110

期号：43

起止页码：17273

外文期刊名：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000325943300034)】；

基金：We thank Amanda Ly for the acetylcholinesterase activity assays; Breanna Morris and Tami Swenson for the cytochrome P450 metabolism experiments; Nanyang Chen for help in the synthesis of prop-2-yn-1-yl propyl phenylphosphonate (PPP) derivatives; Ellen Key and Yan Xu for assistance in experiments and manuscript preparation; and Ernest Hodgson, Robert Hollingworth, and David Soderlund for helpful comments on the manuscript. This study was supported in part by the National High Technology Research Development Program of China (2011AA10A207), Key Projects of the National Science and Technology Pillar Program of China (2011BAE06B05), and the National Natural Science Foundation of China (21002030) (for funding the synthesis of [3H] nitromethyleneimidazole, cycloxaprid, nitromethyleneimidazole, and PPP derivatives); and a Shanghai Education Committee Fellowship (to X.S.).

语种：英文

摘要：The nicotinic acetylcholine (ACh) receptor (nAChR) is the principal insecticide target. Nearly half of the insecticides by number and world market value are neonicotinoids acting as nAChR agonists or organophosphorus (OP) and methylcarbamate (MC) acetylcholinesterase (AChE) inhibitors. There was no previous evidence for in vivo interactions of the nAChR agonists and AChE inhibitors. The nitromethyleneimidazole (NMI) analog of imidacloprid, a highly potent neonicotinoid, was used here as a radioligand, uniquely allowing for direct measurements of house fly (Musca domestica) head nAChR in vivo interactions with various nicotinic agents. Nine neonicotinoids inhibited house fly brain nAChR [H-3]NMI binding in vivo, corresponding to their in vitro potency and the poisoning signs or toxicity they produced in intrathoracically treated house flies. Interestingly, nine topically applied OP or MC insecticides or analogs also gave similar results relative to in vivo nAChR binding inhibition and toxicity, but now also correlating with in vivo brain AChE inhibition, indicating that ACh is the ultimate OP- or MC-induced nAChR active agent. These findings on [H-3]NMI binding in house fly brain membranes validate the nAChR in vivo target for the neonicotinoids, OPs and MCs. As an exception, the remarkably potent OP neonicotinoid synergist, O-propyl O-(2-propynyl) phenylphosphonate, inhibited nAChR in vivo without the corresponding AChE inhibition, possibly via a reactive ketene metabolite reacting with a critical nucleophile in the cytochrome P450 active site and the nAChR NMI binding site.