Cully D F, Vassilatis D K, Liu K K, Paress P S, Van der Ploeg L H, Schaeffer J M, Arena J P
Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065-0900.
Nature. 1994 Oct 20;371(6499):707-11. doi: 10.1038/371707a0.
The avermectins are a family of macrocyclic lactones used in the control of nematode and arthropod parasites. Ivermectin (22,23-dihydroavermectin B1a) is widely used as an anthelmintic in veterinary medicine and is used to treat onchocerciasis or river blindness in humans. Abamectin (avermectin B1a) is a miticide and insecticide used in crop protection. Avermectins interact with vertebrate and invertebrate GABA receptors and invertebrate glutamate-gated chloride channels. The soil nematode Caenorhabditis elegans has served as a useful model to study the mechanism of action of avermectins. A C. elegans messenger RNA expressed in Xenopus oocytes encodes an avermectin-sensitive glutamate-gated chloride channel. To elucidate the structure and properties of this channel, we used Xenopus oocytes for expression cloning of two functional complementary DNAs encoding an avermectin-sensitive glutamate-gated chloride channel. We find that the electrophysiological and structural properties of these proteins indicate that they are new members of the ligand-gated ion channel superfamily.
阿维菌素是一类用于控制线虫和节肢动物寄生虫的大环内酯类药物。伊维菌素（22,23-二氢阿维菌素B1a）在兽医学中广泛用作驱虫药，并用于治疗人类的盘尾丝虫病或河盲症。阿维菌素B1a是一种用于作物保护的杀螨剂和杀虫剂。阿维菌素与脊椎动物和无脊椎动物的GABA受体以及无脊椎动物的谷氨酸门控氯离子通道相互作用。土壤线虫秀丽隐杆线虫已成为研究阿维菌素作用机制的有用模型。在非洲爪蟾卵母细胞中表达的秀丽隐杆线虫信使核糖核酸编码一种对阿维菌素敏感的谷氨酸门控氯离子通道。为了阐明该通道的结构和特性，我们利用非洲爪蟾卵母细胞对编码对阿维菌素敏感的谷氨酸门控氯离子通道的两个功能性互补DNA进行表达克隆。我们发现这些蛋白质的电生理和结构特性表明它们是配体门控离子通道超家族的新成员。
