Nifedipine and nicardipine potentiate glucagon-stimulated glycogenolysis in primary cultures of rat hepatocytes.
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.
Ogihara
M
M
Biochemical Pharmacology Group, Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009529:Nicardipine / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology*; D010208:Papaverine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D002110:Caffeine; D006003:Glycogen; D005934:Glucagon; D009529:Nicardipine; D010208:Papaverine; D000242:Cyclic AMP; D009543:Nifedipine; D015056:1-Methyl-3-isobutylxanthine