Furutani Shogo, Nakatani Yuri, Miura Yuka, Ihara Makoto, Kai Kenji, Hayashi Hideo, Matsuda Kazuhiko
Department of Applied Biological Chemistry, Faculty of Agriculture, Kinki University, 3327-204 Nakamachi, Nara 631-8505, Japan.
Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-chou, Naka-ku, Sakai, Osaka 599-8531, Japan.
Sci Rep. 2014 Aug 26;4:6190. doi: 10.1038/srep06190.
In 1989, indole alkaloid okaramines isolated from the fermentation products of Penicillium simplicissimum were shown to be insecticidal, yet the mechanism of their toxicity to insects remains unknown. We therefore examined the action of okaramine B on silkworm larval neurons using patch-clamp electrophysiology. Okaramine B induced inward currents which reversed close to the chloride equilibrium potential and were blocked by fipronil. Thus it was tested on the silkworm RDL (resistant-to-dieldrin) γ-aminobutyric-acid-gated chloride channel (GABACl) and a silkworm L-glutamate-gated chloride channel (GluCl) expressed in Xenopus laevis oocytes. Okaramine B activated GluCl, but not RDL. GluCl activation by okaramines correlated with their insecticidal activity, offering a solution to a long-standing enigma concerning their insecticidal actions. Also, unlike ivermectin, okaramine B was inactive at 10 μM on human α1β2γ2 GABACl and α1β glycine-gated chloride channels and provides a new lead for the development of safe insect control chemicals.
1989年，从简单青霉发酵产物中分离出的吲哚生物碱奥卡胺被证明具有杀虫作用，但其对昆虫的毒性机制仍不清楚。因此，我们使用膜片钳电生理学研究了奥卡胺B对家蚕幼虫神经元的作用。奥卡胺B诱导内向电流，该电流在接近氯离子平衡电位时反转，并被氟虫腈阻断。因此，我们在非洲爪蟾卵母细胞中表达的家蚕RDL（抗狄氏剂）γ-氨基丁酸门控氯离子通道（GABACl）和家蚕L-谷氨酸门控氯离子通道（GluCl）上对其进行了测试。奥卡胺B激活了GluCl，但未激活RDL。奥卡胺对GluCl的激活与其杀虫活性相关，为长期以来关于其杀虫作用的谜团提供了解决方案。此外，与伊维菌素不同，奥卡胺B在10μM浓度下对人α1β2γ2 GABACl和α1β甘氨酸门控氯离子通道无活性，为开发安全的昆虫控制化学品提供了新的线索。
