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.
Ogihara
M
M
Biochemical Pharmacology Group, Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D000242:Cyclic AMP / Q000378:metabolism; D004357:Drug Synergism; D005943:Gluconeogenesis / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D016895:Culture Media, Serum-Free; D007773:Lactates; D019344:Lactic Acid; D009529:Nicardipine; D000242:Cyclic AMP; D009543:Nifedipine; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine