PREJUNCTIONAL ACTIONS OF MUSCLE-RELAXANTS - SYNAPTIC VESICLES AND TRANSMITTER MOBILIZATION AS SITES OF ACTION

1. Nicotinic antagonists such as tubocurarine affect acetylcholine rel ease from motor nerve terminals at the neuromuscular junction. 2. Elec trophysiological studies comparing the prejunctional actions of tubocu rarine to those of vesamicol and vecuronium have been used to provide an insight into the mechanisms involved in the prejunctional effects o f tubocurarine-like compounds. 3. The observed prejunctional actions o f tubocurarine can be accounted for by a model in which the compound h as two separately identifiable effects on the nerve terminal. At low f requencies of nerve stimulation tubocurarine augments acetylcholine re lease while at high frequencies of nerve stimulation tubocurarine depr esses acetylcholine release. 4. Both of the effects of tubocurarine on acetylcholine release are a consequence of a change in the number of quanta within the nerve terminal immediately available for release upo n nerve stimulation. 5. On the basis of our experimental observations, we suggest that the two prejunctional effects of tubocurarine are med iated through two pharmacologically distinct prejunctional nAChRs.