TOXIC EFFECT OF CHLORINATED AND PYRETHROID PESTICIDES

我们计划研究氯化和拟除虫菊酯杀虫剂的毒性效应。 主要是神经系统中钠和钙的调节过程。 为了研究这些农药对钠转运特异性抗体的影响 针对钠离子通道的蛋白将被获得。通过使用 抗体，杀虫剂与钠通道的直接相互作用 将会被研究。互动的标准将是具有约束力的、竞争的 针对已知的配体如藜芦素、苯妥英、RO5-4864等， 天然和外源蛋白激酶的磷酸化及其抑制 钙-钙调蛋白效应。研究这些农药对人体健康的影响 钙调节过程，我们计划使用突触体的准备来自 哺乳动物脑(主要是大鼠)和无脊椎动物中枢神经系统 (主要是鱿鱼)。最初的研究标准将是刺激 神经递质的释放，特别是由二型拟除虫菊酯引起的。 两个主要的研究目标是：内质网中的CA-MG ATPase和 钙调素刺激的蛋白激酶。在后者的情况下， 各种底物蛋白(例如，突触素I，轻链肌球蛋白，微管蛋白， 等)将被检查以查看某些特定的磷酸化步骤 都受到蛋白激酶变化的影响。

We plan to study toxic effects of chlorinated and pyrethroid pesticides mainly on sodium and calcium regulating processes in the nervous system. To study these pesticide effects on sodium transport specific antibodies directed against sodium channel proteins will be obtained. By using the antibodies, direct interactions of the pesticides with the sodium channels will be studied. The criteria of interactions will be binding, competition against known ligands such as veratridin, phenytoin, RO5-4864, etc., phosphorylation by native and exogenous protein kinases and inhibition of calcium-calmodulin effects. To study the effects of these pesticides on calcium regulatory processes, we plan to use synaptosomal preparations from mammalian brains (mainly rats) and invertebrate central nervous systems (mainly squid). The initial study criterion will be the stimulation of the neurotransmitter release, particularly that caused by Type II pyrethroids. Two major study targets are: Ca-Mg ATPase in the endoplasmic reticulum and calcium-calmodulin-stimulated protein kinase. In the case of the latter, various substrate proteins (e.g., synapsin I, light chain myosin, tubulin, etc.) will be examined to see whether some specific phosphorylation steps are being affected by the changes in the protein kinases.