1993 Volume 16 Issue 8 Pages 771-773
The effects of nifedipine and nicardipine on isoproterenol-stimulated gluconeogenesis from 10mM lactate were examined in serum-free cultures of rat hepatocytes. Nifedipine and nicardipine (10-7-10-5M) significantly potentiated the isoproterenol-stimulated gluconeogenesis from 10mM lactate by increasing intracellular cAMP levels. In contrast, diltiazem and verapamil (10-7-10-6M) did not potentiate it. 1-Methyl-3-isobutylxanthine (IBMX; 10-6-10-4M), 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.