This research project studies how cells, particularly cultured muscle and nerve, recover from poisoning by organophosphate agents such as paraoxon and DFP. The research focuses on how these agents alter regulation of acetylcholinesterase (ACHE) and other molecules of the neuromuscular junction, and on their effects on general protein synthesis and degradation. Next year we are examining (a) whether cell degradation is altered by paraoxon, (b) whether AChE behaves like a secretory protein during its release from the cell, (c) the fate of pesticide-inhibited AChE molecules, (d), localization of AChE forms in muscle and nerve and (e) the idea that pesticides affect a "regulatory receptor" system that controls levels of AChE and other molecules of the neuromuscular junction. The importance of the research is in what it tells us about how cells recover from poisoning by pesticides and how they regulate the levels and location of molecules at the neuromuscular junction. Past research on this project has revealed a system that helps detoxify organophosphates and future research is designed to find out the mechanism by which this occurs.