Postsynaptic facilitatory effects of theophylline on amphibian neuromyal transmission

This study concerns the effects of theophylline on nerve-muscle transmission of the frog; it was of particular interest to evaluate the facilitatory actions of theophylline at the postsynaptic sites. At concentrations of up to 5 mM, theophylline exerted negligible effects on the end-plate resting potential or on the passive membrane characteristics. The major effects of theophylline (0.5--5.0 mM) were exerted on the end-plate potentials (EPPs), miniature EPPs, acetylcholine (ACh) potentials, and on the end-plate current. The amplitude of these parameters was markedly increased; furthermore, the half-decay time of the EPP and, particularly, of the end-plate current were markedly affected. On the other hand, the time course of the ACh potentials was not significantly affected by theophylline. Spontaneous and evoked release of ACh were not affected by theophylline (0.5--5 mM). Altogether, these results indicate that, in amphibia, the neuromyal facilitation induced by theophylline is mainly due to its postsynaptic actions. Furthermore, some of these data as well as results of others indicate that these effects of theophylline are not due to its anticholinesterase properties. It is suggested that theophylline may act directly on the cholinergic receptor or ionic conductance modulator and that it may stabilize the ACh-receptor complex.