Mechanism of relaxant action of papaverine. VI. Sodium ion dependence of its effect on 45Ca-efflux in guinea-pig taenia coli.

The present study was undertaken to investigate the roles of sodium ion and the cyclic AMP system in the relaxant effect of papaverine. The effects of papaverine on the 45Ca-efflux and the mechanical activity of guinea-pig taenia coli were tested in solutions in which the concentration of sodium ion was varied and compared with those of dibutyryl cyclic AMP. Papaverine dose-dependently caused an acceleration of 45Ca-efflux and the synchronous relaxation of a depolarized preparation in normal bathing solution. Dibutyryl cyclic AMP mimicked these effects of papaverine. In Na-free solution, papaverine lost its ability to accelerate the 45Ca-efflux, and its relaxant activity was markedly reduced, while dibutyryl cyclic AMP had neither an effect on the 45Ca-efflux nor an effect on the muscle relaxation in Na-free solution. Reintroduction of a small amount of sodium ion to the solution, however, recovered these effects of papaverine and dibutyryl cyclic AMP on the 45Ca-efflux and the muscle relaxation. These findings indicate that the relaxant effect of papaverine may be in part due to an increase in cyclic AMP-mediated Ca-efflux which requires the presence of external sodium ion. The sodium ion dependence of this Ca-efflux process was also discussed.