Effect of protein synthesis inhibitors on the trophic action of the nerve stump.

We report that protein synthesis inhibitors exert an inhibitory effect on the trophic action of the nerve stump. The sciatic nerve innervating the extensor digitorum longus muscles of mice was cut either as close to, or as far from, the muscle as possible. Denervation changes in the muscle were evaluated using the resting membrane potential and dose-response curves obtained by plotting acetylcholine-induced contractures. Actinomycin D (2 micrograms/kg, i.p.), ethidium bromide (10 micrograms/kg, i.p.), cycloheximide (1 or 5 mg/kg, i.p.), or chloramphenicol (100 mg/kg, p.o.) administration was immediately after neurotomy and continued daily until the day preceding muscle removal. Although denervation changes occurred significantly later in muscles with a long rather than a short nerve stump, the administrated antibiotics, excluding cycloheximide, accelerated the manifestation of denervation changes in muscles with long nerve stumps without affecting those in muscles with short nerve stumps.