INSECTICIDE ACTIONS ON NICOTINIC ACETYLCHOLINE RECEPTORS

描述（由申请人提供）：烟碱乙酰胆碱受体（nAChR）是合成的烟碱类杀虫剂（称为烟碱类）的靶标。拟议的工作将详细研究两种选定的烟碱类化合物，吡虫啉和噻虫胺，与人类肌肉（a <$de）和神经元型（a4 <$2）nAChR的相互作用。有两个目标。第一个目的是建立由吡虫啉和噻虫胺的肌肉型nAChR的激活和调制的属性。第二个目的是确定神经元型nAChR调制的机制，由吡虫啉和噻虫胺。这些结果将有助于更好地定义杀虫剂毒性的机制，并可能有助于学习如何提供对类烟碱的保护，以及为设计新型，更高选择性的类烟碱提供见解。 公共卫生相关性：新烟碱类化合物是合成的尼古丁化合物，用作许多广泛使用的杀虫剂的活性成分。在哺乳动物中，暴露于类烟碱可导致震颤和缺乏协调。烟碱型乙酰胆碱受体是类尼古丁在哺乳动物中的主要靶点。拟议的工作将检查两个选定的烟碱类，吡虫啉和噻虫胺，对nAChR的作用机制。

DESCRIPTION (provided by applicant): The nicotinic acetylcholine receptor (nAChR) is the target of synthetic, nicotine-based insecticides, called neonicotinoids. The proposed work will examine in detail the interactions of two selected neonicotinoids, imidacloprid and clothianidin, with human muscle (a¿de) and neuronal-type (a4¿2) nAChR. There are two aims. The first aim is to establish the properties of activation and modulation by imidacloprid and clothianidin of the muscle-type nAChR. The second aim is to determine the mechanisms of neuronal-type nAChR modulation by imidacloprid and clothianidin. The results will help to better define the mechanisms of insecticide toxicity, and may be useful in learning how to provide protection from neonicotinoids, as well as provide insights into designing novel, more highly selective neonicotinoids. PUBLIC HEALTH RELEVANCE: Neonicotinoids are synthetic, nicotine-based compounds used as the active ingredients in many widely used insecticides. In mammals, exposure to neonicotinoids can result in tremors and lack of coordination. The nicotinic acetylcholine receptor is the major target of neonicotinoids in mammals. The proposed work will examine the mechanisms of action of two selected neonicotinoids, imidacloprid and clothianidin, on the nAChR.