Ogihara M
Biochemical Pharmacology Group, Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
Biol Pharm Bull. 1993 Aug;16(8):771-3. doi: 10.1248/bpb.16.771.
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.
在大鼠肝细胞的无血清培养中，研究了硝苯地平和尼卡地平对异丙肾上腺素刺激的、由10 mM乳酸生成葡萄糖的影响。硝苯地平和尼卡地平（10⁻⁷ - 10⁻⁵ M）通过提高细胞内cAMP水平，显著增强了异丙肾上腺素刺激的、由10 mM乳酸生成葡萄糖的过程。相比之下，地尔硫卓和维拉帕米（10⁻⁷ - 10⁻⁶ M）则没有增强这一过程。已知可抑制磷酸二酯酶活性的1-甲基-3-异丁基黄嘌呤（IBMX；10⁻⁶ - 10⁻⁴ M），在大鼠肝细胞的无血清培养中，剂量依赖性地增强了异丙肾上腺素刺激的、由乳酸生成葡萄糖的过程。同时，IBMX也以剂量依赖性方式增加了异丙肾上腺素诱导的细胞内cAMP浓度。这些结果表明，硝苯地平和尼卡地平增强异丙肾上腺素刺激的糖异生的可能机制与通过抑制cAMP磷酸二酯酶增加cAMP水平有关。
