谷氨酸激活的氯离子通道：昆虫特有的氟虫腈作用靶点，在哺乳动物中不存在。

Glutamate-activated chloride channels: Unique fipronil targets present in insects but not in mammals.

作者信息

Narahashi Toshio, Zhao Xilong, Ikeda Tomoko, Salgado Vincent L, Yeh Jay Z

机构信息

Department of Molecular Pharmacology and biological Chemistry Northwestern University Feinberg School of Medicine 303 E. Chicago Avenue, Chicago, IL 60611.

出版信息

Pestic Biochem Physiol. 2010 Jun 1;97(2):149-152. doi: 10.1016/j.pestbp.2009.07.008.

Selectivity to insects over mammals is one of the important characteristics for a chemical to become a useful insecticide. Fipronil was found to block cockroach GABA receptors more potently than rat GABA(A) receptors. Furthermore, glutamate-activated chloride channels (GluCls), which are present in cockroaches but not in mammals, were very sensitive to the blocking action of fipronil. The IC(50)s of fipronil block were 30 nM in cockroach GABA receptors and 1600 nM in rat GABA(A) receptors. Moreover, GluCls of cockroach neurons had low IC(50)s for fipronil. Two types of glutamate-induced chloride current were obswerved: desensitizing and non-desensitizing, with fipronil IC(50)s of 800 and 10 nM, respectively. We have developed methods to separately record these two types of GluCls. The non-desensitizing and desensitizing currents were selectively inhibited by trypsin and polyvinylpyrrolidone, respectively. In conclusion, in addition to GABA receptors, GluCls play a crucial role in selectivity of fipronil to insects over mammals. GluCls form the basis for development of selective and safe insecticides.

对昆虫而非哺乳动物的选择性是一种化学物质成为有用杀虫剂的重要特性之一。人们发现氟虫腈阻断蟑螂GABA受体的能力比大鼠GABA(A)受体更强。此外，谷氨酸激活的氯离子通道（GluCls）存在于蟑螂中但不存在于哺乳动物中，对氟虫腈的阻断作用非常敏感。氟虫腈阻断的半数抑制浓度（IC(50)）在蟑螂GABA受体中为30 nM，在大鼠GABA(A)受体中为1600 nM。此外，蟑螂神经元的GluCls对氟虫腈的半数抑制浓度较低。观察到两种类型的谷氨酸诱导的氯离子电流：脱敏型和非脱敏型，氟虫腈对它们的半数抑制浓度分别为800和10 nM。我们已经开发出分别记录这两种类型GluCls的方法。非脱敏电流和脱敏电流分别被胰蛋白酶和聚乙烯吡咯烷酮选择性抑制。总之，除了GABA受体外，GluCls在氟虫腈对昆虫而非哺乳动物的选择性中起关键作用。GluCls构成了开发选择性和安全杀虫剂的基础。