Mechanism of Relaxant Action of Papaverine VI. Sodium Ion Dependence of Its Effect on 45Ca-Efflux in Guinea-Pig Taenia Coli

Abstract

The mode of action of papaverine on smooth muscle relaxation was examined through analyzing its effects on caffeine-induced contraction of guinea pig taenia coli, which might be due to calcium ion mobilized from intracellular store sites. Caffeine contraction induced in normal solution at 32 degrees C was decreased in the presence of papaverine but increased after the removal of papaverine, and it was also increased when the muscle was preincubated with papaverine and then washed out. These papaverine actions were inhibited at low temperature. Caffeine contraction induced in Ca-free, depolarizing solution was also enhanced by treatment with papaverine during Ca-loading. Cyclic AMP and its dibutyryl derivative produced a similar effect on the caffeine contraction induced in normal or Ca-free, depolarizing solution as those of papaverine. In addition, a good correlation was observed between the papaverine-induced increases in caffeine response and in tissue cyclic AMP level. From these results, it is considered that papaverine increases cyclic AMP of the taenia coli, and this increased cyclic AMP stimulates accumulation of calcium ion into its storage sites from where calcium ion was released by caffeine, finally leading to smooth muscle relaxation.