EFFECTS OF PHOSPHODIESTERASE INHIBITORS ON SPONTANEOUS ELECTRICAL-ACTIVITY (SLOW WAVES) IN THE GUINEA-PIG GASTRIC MUSCLE

1. The effects of the phosphodiesterase inhibitors caffeine, theophyll ine, isobutylmethylxanthine (IBMX) and rolipram on spontaneous electri cal activity (slow waves) were studied in the circular muscle of the g uinea-pig gastric antrum. 2. All the inhibitors reduced slow wave freq uency without changing the membrane potential and the slow wave config uration, but at higher concentrations they blocked the slow waves and caused membrane hyperpolarization. In the presence of the inhibitors a low level of irregular electrical activity could be observed in many preparations. 3. Isoprenaline, forskolin, dibutyryl cAMP and 8-bromo-c AMP all produced effects essentially similar to those of phosphodieste rase inhibitors. K+ (12 mM) and removal of K+ both depolarized the mem brane and these were not affected by IBMX (1-3 mu M). A decrease in fr equency caused by IBMX was also not significantly affected by 12 mM K or K+ removal and only partially antagonized by TEE or 4-aminopyridin e. 4. These results suggest that an increase in intracellular cAMP inh ibits pacemaker activity of slow waves. An increase in K+ conductance does not seem to be a major factor in this inhibition. Slow waves appe ar to be a compound electrical activity in a group of muscle cells and are likely to be disintegrated by xanthine derivatives.