Mg++ antagonism of a prejunctional opiate receptor mediated effect at the frog neuromuscular junction

The effect of meperidine on the spontaneous release of acetylcholine (mepp amplitude and frequency) and on the release evoked by nerve stimulation (epp amplitude and quantal content) was investigated in frog sciatic nerve-sartorius muscle in vitro. Meperidine (8.5 X 10(-5) or 1.6 X 10(-4)M) had no effect on mepp frequency recorded intracellularly in the absence of neuromuscular blockers, but reduced mepp amplitude. This depression was not antagonized by 3 X 10(-8) M naloxone and was explained by a nonspecific depressant action of meperidine on the endplate. When mepps and epps were recorded intracellularly in the presence of high Mg++, the mean amplitudes of both potentials were reduced equally by meperidine (either 1.6 or 4.2 X 10(-4)M) i.e. there was no change in the quantal content, and 3 X 10(-8)M naloxone failed to antagonize these amplitude depressions. When epps were recorded in the presence of d-tubocurarine, the percentage depression of epp amplitude by meperidine was significantly greater than found in the presence of Mg++ and was partially antagonized by naloxone indicating an opiate receptor mediated effect of meperidine. Thus it was concluded that Mg++ prevents this prejunctional opiate receptor mediated depressant effect of meperidine on the evoked release of acetylcholine.