[Action of cyclic nucleotide phosphodiesterase inhibitors on the acetylcholine potential].

A study was made of the action of theophylline, isobutyrylmethylxanthine and caffeine on the sensitivity of mouse diaphragmatic muscle fibers to iontophoretically applied acetylcholine (ACh). It was shown that these substances at concentrations of 5 X 10(-4) -5 X 10(-3) M reduced the amplitude and increased the duration of the ACh potential as well as accelerated desensitization of the cholinoceptor at repetitive application of ACh. As regards the action on the ACh potential amplitude two phases which differed in the time-course of development and washing were recognized: rapid and slow. Addition of dibutyryl-cAMP (5 X 10(-4) M) after theophylline (10(-3) M) potentiated the latter's action on the ACh potential amplitude but did not influence its duration and the rate of desensitization. It is assumed that the action of phosphodiesterase inhibitors on the duration of the ACh potential and the rate of desensitization is not mediated by an elevation in the muscle cAMP content. Apparently, cAMP accumulation may be responsible but for the phase of a slow decrease in the ACh potential amplitude.