Functional interactions of calcium-antagonists in K+-depolarized smooth muscle

The functional significance of the interaction of certain calcium-antagonists with nimodipine was examined so that this might be related to binding studies. To this end, the relaxant effects of nimodipine (1-100 nM) on Ca2+ (10 mM)-induced contractions of K+-depolarized taenia preparations from the guinea-pig caecum were compared in the presence of nifedipine and cinnarizine (which competitively displace [3H]-nimodipine with high and low affinities respectively), diltiazem (which increases binding), verapamil (which allosterically reduces binding) and W-7, a calmodulin antagonist. The relaxant effects of nimodipine were similar in the presence of nifedipine, diltiazem and cinnarizine, but were slightly attenuated in the presence of verapamil and W-7. These findings can be reconciled with the differentiation of calcium antagonists evident from [3H]-nimodipine binding studies, but indicate that the functional consequences of allosteric interactions disclosed in such studies are small. Drugs which bind to calcium channels and drugs which bind to calmodulin did not potentiate each other.