Paraoxon, an irreversible inhibitor of organophosphorous cholinesterase, produces necrosis in innervated skeletal muscle. Because fast axoplasmic transport of protein has been suggested as a vehicle for maintenance of normal muscle properties, it is possible that it is involved in the muscle-damaging effect of the drug. To clarify this role, we have examined the effect of this drug on cholinesterase activity and fast axoplasmic transport of enzyme by measuring enzyme accumulation proximal to ligations of rat sciatic nerve. The results show that, in normal animals, fast axoplasmic transport of a small amount of available enzyme occurs at approximately 400 mm/day. Paraoxon treatment causes a significant reduction of enzyme activity in both muscle and nerve. The return of enzyme activity in muscle is rapid and continuous, whereas in nerve only a small recovery is seen during the first 2 hr after treatment. This difference in recovery of enzyme activity suggests that return of axonal enzyme occurs via somal synthesis and axoplasmic transport. The data also suggest that, although paraoxon is an effective inhibitor of cholinesterase, it does no alter fast axoplasmic transport of enzyme.
