In this research project we propose to study toxic effects of chlorinated and pyrethroid pesticides mainly on calcium regulating processes in the nervous system, the liver and the heart. The main experimental animals to be used is the rat, but the mouse, the guinea pig, the hamster and some inverterbrate species will also be used. The compounds mainly studied are DDT, toxaphene, chlordane, dieldrin aldrin, neptachlor, neptachlor epoxide, allethrin, permethrin, fenvalerate cypermetnrin and decamethrin. In the case of the liver, the major emphasis will be placed on the long term effects of these chemicals on calcium transport functions of hepatocytes. Also an effort will be made to study their effects on the gap-junction which is known to be controlled by calcium concentration for its functions. The extents of the influence of these pesticides on cell-cell recognition and communication will be determined. In the case of the nervous system, we plan to study their influence on various calcium regulating systems such as Na-Ca exchange, particularly the portion relating to ATP utilization, and on Ca-Mg ATPase. In the latter case changes in its interaction with calmodulin as well as in transmitter release, and neurosecretion will be examined. As for cyclodience-type chlorinated presticides we plan to examine their effects on GABA-chloride channel systems. A particular emphasis will be placed on the studies on the picrotoxinin receptor. This project will also cover the area of pesticide effects on cardiac biochemistry especially as related to their influence on calcium regulation.
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