MECHANISM OF RELAXANT ACTION OF PAPAVERINE. III. COMPARISON OF SODIUM ION DEPENDENCIES ON THE RELAXANT EFFECTS OF PAPAVERINE, ASPAMINOL AND BENACTYZINE IN GUINEA-PIG TAENIA COLI

The role of sodium ion on the relaxant action of papaverine in guinea-pig taenia coli contracted by hypertonic 40 mM KCl were studied by manipulating the external soidum ion concentration and compared with those of its allied antispasmodics, Aspaminol and benactyzine. Whereas all of the three antispasmodics relaxed the taenia in all media used herein, their relaxant activities were declined by eliminating sodium ion from the bathing media. The declined relaxant activities were restored by re-introducing sodium ion to the solution depending on the amount of sodium ion but sodium ion dependencies of the restoration were not equal for each. In a solution containing 20 mM sodium ion, almost complete restoration was encountered with papaverine, while displayed only a slight restoration with Aspaminol and benactyzine. When a small amount of sodium ion was applied to the taenia before or after the treatment with the antispasmodics, the relaxation in response to papaverine was augmented, but those in response to Aspaminol and benactyzine were not affected. All of the three antispasmodics inhibited the cellular 45Ca-uptake in all media. While their inhibitory activities were reduced by eliminating sodium ion from the media and were not restored so markedly by re-introducing 20 mM sodium ion to the solution. From these findings, it is suggested that papaverine may induce the smooth muscle relaxation not only by inhibiting the Ca-influx independently of the presence of sodium ion but also by other mechanisms sensitive to sodium ion, by contrast, Aspaminol and benactyzine may evoke the relaxation through mechanisms less sensitive to the presence of sodium ion, which include the inhibition of Ca-influx. Since the ability of papaverine to increase the cellular cyclic AMP content remained unchanged even in the Na-free solution, parts of cyclic AMP on the sodium ion sensitive mechanisms were also duscussed.