Nifedipine and Nicardipine Potentiate Glucagon-Stimulated Glycogenolysis in Primary Cultures of Rat Hepatocytes

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The effects of two calcium channel blockers, nifedipine and nicardipine, on glucagon-stimulated glycogenolysis in primary cultures of rat hepatocytes were examined in vitro. When nifedipine and nicardipine (10^<-7>-10^<-6>M) were added to the incubation mixture with various concentrations of glucagon (10^<-10>-10^<-6>M), these dihydropyridine calcium channel blockers significantly potentiated the glycogenolytic action of glucagon by increasing intracellular cAMP levels. 1-Methyl-3-isobutylxanthine (IBMX), caffeine and papaverine, which is known to inhibit cAMP phosphodiesterase, also potentiated the stimulatory effect of glucagon on the glycogenolysis in a dose-dependent manner. Parallel to the potentiation of glycogenolysis, IBMX also increased the glucagon-stimulated intracellular cAMP levels in a dose-dependent manner. These results suggest that the mechanism of potentiation of the glucagon-stimulated glycogenolysis by nifedipine and nicardipine is related to the known inhibition of cAMP phosphodiesterase by these agents.
公益社団法人日本薬学会の論文
1993-09-15