INSECTICIDE ACTIONS ON NICOTINIC ACETYLCHOLINE RECEPTORS

描述（由申请人提供）：烟碱乙酰胆碱受体（nAChR）是合成的基于尼古丁的杀虫剂，称为新烟碱类杀虫剂的靶标。拟议的工作将详细研究两种选定的新烟碱类，吡虫啉和噻虫胺，与人体肌肉（a¿de）和神经元型（a4¿2）nAChR的相互作用。有两个目的。第一个目的是确定吡虫啉和噻虫胺对肌型nAChR的激活和调节特性。第二个目的是确定吡虫啉和噻虫胺对神经元型nAChR的调节机制。这些结果将有助于更好地确定杀虫剂的毒性机制，并可能有助于了解如何对新烟碱类杀虫剂提供保护，以及为设计新的，更具高选择性的新烟碱类杀虫剂提供见解。

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.