INHIBITORY-ACTION OF NICOTINIC ANTAGONISTS ON TRANSMITTER RELEASE AT THE NEUROMUSCULAR-JUNCTION OF THE RAT

The effects of two nicotinic antagonists, d-tubocurarine (TC) and hexa methonium (HEX) were tested on the rat diaphragm neuromuscular junctio n during train-of-six stimuli to determine if a second action of these antagonists on evoked release could be demonstrated, in addition to i ts known impact of blocking the autoreceptor pathway. To minimize the autoreceptor pathway, the preparations were examined under low transmi tter release conditions. It was observed that both compounds significa ntly depressed the end-plate potential amplitudes more than the miniat ure end-plate potential amplitudes, while also significantly depressin g quantal release output. This inhibitory action is contrary to what i s observed when transmitter release is high, where feedback regulation via the autoreceptors serves a prominent role. It is concluded that t his depressive action on transmitter output contributes to onset of te tanic fade and that when higher concentrations of these antagonists ar e used this inhibitory action of TC and HEX may override autoreceptor feedback regulation.