GABAERGIC INSECTICIDE TOXICOLOGY

伽巴能杀虫剂毒理学

基本信息

  • 批准号:
    6125189
  • 负责人:
  • 金额:
    $ 22.63万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1998
  • 资助国家:
    美国
  • 起止时间:
    1998-12-01 至 2002-11-30
  • 项目状态:
    已结题

项目摘要

The long-term objective is to define the fundamental basis for the selective toxicity of insecticides acting at the gamma-aminobutyric acid (GABA) receptor of mammals and insects. This is the target of major neurotoxic insecticides acting as both blockers and activators of the GABA-gated chloride channel. More than 5,000,000,000 pounds of these channel blockers have been used for pest control in the past 50 years and they range in chlorine content from 52-73%. The major channel blockers used at present, representing 6% of the insecticide market, are endosulfan and lindane and this market share will increase with expanded use of the newly-commercialized polyhalogenated fipronil. The activators such as avermectin and moxidectin are also used in ever increasing quantities as insecticides and anthelmintics. More specifically, the goal is to provide toxicological profiles and maps for the insecticide blocker site and the insecticide activator site by designing and using high-affinity radioligands (the insecticide itself or a closely-related model compound) and photoaffinity probes to study binding site interactions and localization in the brain and chloride channel. Emphasis will be placed on the discovery of differences between the GABA receptors of mammals and insects that confer preferential sensitivity to insecticides and safety to mammals. The proposal is to prepare suitable radioligands and photoaffinity probes and use them to localize the binding sites as to brain region, receptor subunit and specific derivatized amino acid(s) in the chloride channel of mammals (bovine) and insects (Drosophila); the chemistry to achieve this end comes largely from discoveries in this laboratory. The research also involves rat cerebellar granule cells in primary culture to study radioligand binding and chloride flux in intact cells, localization of radioligand binding in mouse brain slices following in vitro and in vivo exposure to unlabeled toxicants, and receptors derived from Sf9 cells transfected with cDNs of human GABAa receptor subunits.
长期目标是确定基本的基础

项目成果

期刊论文数量(0)
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会议论文数量(0)
专利数量(0)

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JOHN E CASIDA其他文献

JOHN E CASIDA的其他文献

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{{ truncateString('JOHN E CASIDA', 18)}}的其他基金

PHOTOLABELING OF ACETYLCHOLINE BINDING PROTEIN BY NICOTINOIDS & NEONICOTINOIDS
烟碱类化合物对乙酰胆碱结合蛋白进行光标记
  • 批准号:
    8363771
  • 财政年份:
    2011
  • 资助金额:
    $ 22.63万
  • 项目类别:
PHOTOLABELING OF ACETYLCHOLINE BINDING PROTEIN BY NICOTINOIDS & NEONICOTINOIDS
烟碱类化合物对乙酰胆碱结合蛋白进行光标记
  • 批准号:
    8169766
  • 财政年份:
    2010
  • 资助金额:
    $ 22.63万
  • 项目类别:
PHOTOLABELING OF ACETYLCHOLINE BINDING PROTEIN BY NICOTINOIDS & NEONICOTINOIDS
烟碱类化合物对乙酰胆碱结合蛋白进行光标记
  • 批准号:
    7957403
  • 财政年份:
    2009
  • 资助金额:
    $ 22.63万
  • 项目类别:
PHOTOLABELING OF ACETYLCHOLINE BINDING PROTEIN BY NICOTINOIDS & NEONICOTINOIDS
烟碱类化合物对乙酰胆碱结合蛋白进行光标记
  • 批准号:
    7724214
  • 财政年份:
    2008
  • 资助金额:
    $ 22.63万
  • 项目类别:
PHOTOLABELING OF ACETYLCHOLINE BINDING PROTEIN BY NICOTINOIDS & NEONICOTINOIDS
烟碱类化合物对乙酰胆碱结合蛋白进行光标记
  • 批准号:
    7601860
  • 财政年份:
    2007
  • 资助金额:
    $ 22.63万
  • 项目类别:
CHOLINERGIC INSECTICIDE TOXICOLOGY
胆碱能杀虫剂毒理学
  • 批准号:
    6382209
  • 财政年份:
    1998
  • 资助金额:
    $ 22.63万
  • 项目类别:
Cholinergic Insecticide Toxicology
胆碱能杀虫剂毒理学
  • 批准号:
    6929823
  • 财政年份:
    1998
  • 资助金额:
    $ 22.63万
  • 项目类别:
CHOLINERGIC INSECTICIDE TOXICOLOGY
胆碱能杀虫剂毒理学
  • 批准号:
    2622701
  • 财政年份:
    1998
  • 资助金额:
    $ 22.63万
  • 项目类别:
GABAERGIC INSECTICIDE TOXICOLOGY
伽巴能杀虫剂毒理学
  • 批准号:
    6329456
  • 财政年份:
    1998
  • 资助金额:
    $ 22.63万
  • 项目类别:
CHOLINERGIC INSECTICIDE TOXICOLOGY
胆碱能杀虫剂毒理学
  • 批准号:
    6178599
  • 财政年份:
    1998
  • 资助金额:
    $ 22.63万
  • 项目类别:

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