INSECTICIDE ACTIONS ON NICOTINIC ACETYLCHOLINE RECEPTORS

描述(申请人提供)：烟碱型乙酰胆碱受体(NAChR)是以尼古丁为基础的合成杀虫剂的靶标，称为新烟碱。这项拟议的工作将详细研究两种选定的新烟碱类化合物--吡虫啉和氯硫菌素--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。第一个目的是确定吡虫啉和氯硫菌素对肌型nAChR的激活和调制特性。第二个目的是确定吡虫啉和氯硫菌素对神经元型nAChR的调节机制。这些结果将有助于更好地确定杀虫剂毒性的机制，并可能有助于学习如何提供对新烟碱的保护，以及为设计新的、更高选择性的新烟碱提供见解。 与公共卫生相关：新烟碱是一种合成的尼古丁类化合物，用作许多广泛使用的杀虫剂的活性成分。在哺乳动物中，接触新烟碱会导致震颤和缺乏协调性。在哺乳动物中，烟碱型乙酰胆碱受体是新烟碱的主要靶标。这项拟议的工作将研究两种选定的新烟碱类化合物--吡虫啉和衣硫菌素--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.