Opiates inhibit acetylcholine release from Torpedo nerve terminals by blocking Ca2+ influx.

In the present communication we report that Ca2+-dependent acetylcholine release from K+-depolarized Torpedo electric organ synaptosomes is inhibited by morphine, and that this effect is blocked by the opiate antagonist naloxone. This finding suggests that the purely cholinergic Torpedo electric organ neurons contain presynaptic opiate receptors whose activation inhibits acetylcholine release. The mechanisms underlying this opiate inhibition were investigated by comparing the effects of morphine on acetylcholine release induced by K+ depolarization and by the Ca2+ ionophore A23187 and by examining the effect of morphine on 45Ca2+ influx into Torpedo nerve terminals. These experiments revealed that morphine inhibits 45Ca2+ influx into K+-depolarized Torpedo synaptosomes and that this effect is blocked by naloxone. The effects of morphine on K+ depolarization-mediated 45Ca2+ influx and on acetylcholine release have similar dose dependencies (half-maximal inhibition at 0.5-1 microM), suggesting that opiate inhibition of release is due to blockage of the presynaptic voltage-dependent Ca2+ channel. This conclusion is supported by the finding that morphine does not inhibit acetylcholine release when the Ca2+ channel is bypassed by introducing Ca2+ into the Torpedo nerve terminals via the Ca2+ ionophore.