Dual action of meperidine on the frog neuromuscular junction: a prejunctional, opiate receptor-mediated depression of transmitter release and a postjunctional, nonopiate receptor effect on the endplate.

The action of meperidine was investigated on the frog sciatic nerve-sartorius muscle in vitro. Meperidine (5 X 10(-5) M to 2 X 10(-4) M) depressed the twitch response to nerve stimulation but potentiated the response to direct muscle stimulation. When the nerve terminal action potential and the endplate potential (EPP) were recorded simultaneously, the EPP was depressed by meperidine but only a small and variable decrease in the nerve terminal action potential was observed which did not produce the EPP depression. The depression of the EPP was partly antagonized by naloxone (3 X 10(-8) M). Meperidine also depressed the EPP produced by iontophoresis of acetylcholine onto the endplate, but this depression was not antagonized by naloxone. It is concluded that there are two meperidine actions on junctional transmission in this preparation. One, a depression of the prejunctional transmitter release process. This depression is partly, if not completely, opiate receptor-mediated. The second is a depression of the response of the endplate to acetylcholine. The latter effect does not involve a naloxone-sensitive opiate receptor.