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.
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