relationship between cyclic AMP elevating agents and neuromuscular blockers

ABSTRACT

The effects of aminophylline, papaverine and forskolin on the neuromuscular transmission were studied using isolated rat phrenic nerve-diaphragm preparation. These cyclic AMP elevating agents were found to be capable of enhancing the diaphragmatic contractions elicited by indirect electrical stimulation. The paralysis of the indirectly stimulated rat diaphragm induced by d-tubocurarine was inhibited by aminophylline, papaverine and forskolin, while that induced by succinylcholine was deepened. Pretreatment with adenosine inhibited the enhancement effect of aminophylline, papaverine and forskolin on the contractions of the indirectly stimulated rat diaphragm. Doubling the concentration of calcium in the bathing fluid potentiated the effects of the three compounds on the rat phrenic nerve-diaphragm preparations-while doubling the concentration of external magnesium inhibited their effects. The pretreatment with aminophylline, papaverine and forskolin reduced the toxicity of d-tubocuranine in mice. These results suggest that aminophylline, papaverine and forskolin promote neuromuscular transmission, obviously by facilitating the release of acetylcholine. This finding is compatible with the hypothesis that the intracellular accumulation of cyclic AMP may facilitate the calcium influx and transmitter release from the mammalian motor nerve endings