Scott J G
Department of Entomology, Cornell University, Ithaca, NY 14853-0901, USA.
Insect Biochem Mol Biol. 1996 Jul;26(7):645-9. doi: 10.1016/s0965-1748(96)00008-2.
CYP6D1 is a cytochrome P450 responsible for the metabolism of insecticides and other xenobiotics in the house fly (Musca domestica). Using a CYP6D1-specific monooxygenase activity and a non-CYP6D1-specific monooxygenase activity, 21 compounds were evaluated as inhibitors of CYP6D1 in house fly microsomes. CYP6D1 was strongly inhibited by xanthotoxin, chlorpyrifos, beta-naphthoflavone, piperonyl butoxide and 5-methoxypsoralen. The highest selectivity for inhibition of CYP6D1 was seen for 5-methoxypsoralen, xanthotoxin, beta-naphthoflavone, chlorpyrifos oxon, isosafrole and psoralen. The results clearly indicate that identification of isoform-selective inhibitors of P450s within an insect, and across species, is possible. In addition, psoralen and 5-methoxypsoralen stimulated ethoxycoumarin O-deethylation suggesting that these compounds were substrates for monooxygenases in house fly microsomes. Isosafrole was shown to be a potent synergist of pyrethroid insecticides in adult house flies.
CYP6D1是一种细胞色素P450，负责家蝇（Musca domestica）体内杀虫剂和其他外源性物质的代谢。利用CYP6D1特异性单加氧酶活性和非CYP6D1特异性单加氧酶活性，评估了21种化合物作为家蝇微粒体中CYP6D1抑制剂的效果。黄原毒素、毒死蜱、β-萘黄酮、胡椒基丁醚和5-甲氧基补骨脂素对CYP6D1有强烈抑制作用。5-甲氧基补骨脂素、黄原毒素、β-萘黄酮、毒死蜱氧磷、异黄樟素和补骨脂素对CYP6D1的抑制选择性最高。结果清楚地表明，在昆虫体内以及跨物种鉴定细胞色素P450的同工型选择性抑制剂是可能的。此外，补骨脂素和5-甲氧基补骨脂素刺激了乙氧基香豆素O-脱乙基作用，表明这些化合物是家蝇微粒体中单加氧酶的底物。异黄樟素被证明是成年家蝇中拟除虫菊酯类杀虫剂的有效增效剂。
