Potentiation of isoproterenol-stimulated gluconeogenesis in serum-free cultures of rat hepatocytes by nifedipine and nicardipine.

The effects of nifedipine and nicardipine on isoproterenol-stimulated gluconeogenesis from 10 mM lactate were examined in serum-free cultures of rat hepatocytes. Nifedipine and nicardipine (10(-7)-10(-5) M) significantly potentiated the isoproterenol-stimulated gluconeogenesis from 10 mM lactate by increasing intracellular cAMP levels. In contrast, diltiazem and verapamil (10(-7)-10(-6) M) did not potentiate it. 1-Methyl-3-isobutylxanthine (IBMX; 10(-6)-10(-4) M), which is known to inhibit phosphodiesterase activity, dose-dependently potentiated isoproterenol-stimulated gluconeogenesis from lactate in serum-free cultures of rat hepatocytes. In parallel, IBMX also increased the isoproterenol-induced intracellular concentrations of cAMP in a dose-dependent manner. These results suggest that the possible mechanism by which nifedipine and nicardipine potentiate the isoproterenol-stimulated gluconeogenesis is related to the increase of cAMP levels through the inhibition of cAMP phosphodiesterase.