RECEPTORS AS TARGETS FOR INSECTICIDES

在发现有效的昆虫选择性毒药之前，必须保持平衡 建立在需要最大限度地减少对环境的不利影响之间 杀虫剂的使用，以及最大限度地提高 人类。这项提议的长期目标是发展有选择的 对有害昆虫有毒但对哺乳动物安全的杀虫剂， 鸟和鱼。具体目标是了解更多关于专业的知识 昆虫的神经递质受体因其重要的调节作用 对神经和肌肉功能的作用。发现两者之间的差异 这些受体及其在脊椎动物中的对应受体可能被利用来 开发选择性杀虫剂。 将研究三个神经递质受体系统： 蟑螂的乙酰胆碱、谷氨酸和γ-氨基丁酸受体 神经节和家蝇的大脑和骨骼肌。使用的方法是 生化和药理作用。我们采用了两种主要方法来 识别受体：一种是通过它们的结合部位，利用结合 用放射性标记的神经递质或其他受体配体进行分析。这个 另一种是通过它们的功能，利用受体调节的测量 离子传输。这些受体与杀虫剂的相互作用将 确定这些重要蛋白质可能是主要的还是次要的靶标 他们的行为。此外，这些受体与神经毒素的相互作用 在黄蜂和蜘蛛的麻痹毒液中存在的毒剂，以及 将调查食虫性真菌产生的抗生素，以便 指出可能是有效杀虫剂的新结构。重点是 将取决于对我们的生化数据和其他人的利用 比较昆虫神经递质受体的电生理数据 与哺乳动物的差异很大。

Until effective insect-selective poisons are discovered, a balance must be established between the need to minimize the adverse environmental impact of insecticides and the need to maximize the survival and health of humans. The long term objective of this proposal is to develop selective insecticides which are toxic to harmful insects but are safe for mammals, birds and fish. The specific aims are to learn more about major neurotransmitter receptors of insects because of their vital regulatory roles for nerve and muscle functions. Discovery of differences between these receptors and their counterparts in vertebrates may be exploited to develop selective insecticides. Three neurotransmitter receptor systems will be investigated: the acetylcholine, glutamate and Gamma-aminobutyric acid receptors of cockroach ganglia and housefly brain and skeletal muscles. The approach used is biochemical and pharmacological. Two major methods are employed to identify the receptors: One is via their binding sites, utilizing binding assays with radiolabeled neurotransmitters or other receptor ligands. The other is via their functions, utilizing measurements of receptor-regulated ion-transport. Interactions of these receptors with insecticides will determine if these vital proteins may be primary or secondary targets for their actions. In addition, interaction of these receptors with neurotoxic agents present in paralytic venoms of wasps and spiders, and with antibiotics produced by entomophagous fungi will be investigated so as to point to novel structures that may be potent insecticides. The emphasis will be on utilization of our biochemical data and others' electrophysiological data to compare neurotransmitter receptors of insects with those of mammals.