ACTH and neuromuscular transmission: Electrophysiological in vitro investigation of the effects of corticotropin and an ACTH fragment on neuromuscular transmission

The effects of corticotropin (ACTH) and the polypeptide fragment ACTH 4‐10 on neuromuscular transmission were studied in rat phrenic nerve–diaphragm preparations in vitro. ACTH decreased the quantum content of end‐plate potentials (epps) and increased the transmission failure rate. The frequency of miniature end‐plate potentials (mepps) was increased. The results indicate that ACTH acts directly on the presynaptic terminal. The findings could explain the transient decrease in muscle strength often observed during corticotropin therapy for myasthenia gravis, and they suggest that the therapeutic effect of ACTH is indirectly mediated. The only marked effect produced by the ACTH fragment was an increase in the mepp frequency; quantum content and failure rate of epps remained unchanged. Since ACTH 4‐10 is unable to stimulate cortisone release, its clinical efficacy seems unlikely.