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

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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.
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