ACTIVE TRANSPORT OF ION AND SUBSTRATE IN ISOLATED CELLS AND REGULATION MECHANISM OF ENERGY METABOLISM.

在多种激素激动剂的作用下，研究了咖啡因对大鼠离体肝细胞糖异生和尿素生成的影响。4 mM谷氨酰胺的糖异生和尿素合成分别被10 <微> M的苯肾上腺素刺激1.7倍和1.9倍（与对照相比）。添加不同浓度的咖啡因（10 <微> M），苯肾上腺素会根据其浓度引起双相效应，即刺激(<10^（-4)> - <10^(-3)> M）和抑制（大于5 mM咖啡因）。1 mM咖啡因对糖异生和尿素合成的刺激分别为2.1倍和2.4倍。咖啡因的作用取决于苯肾上腺素的作用。不含苯肾上腺素的咖啡因对两种合成都没有影响。咖啡因的作用需要细胞外<Ca^(2+)>的存在，而在没有细胞外<Ca^(2+)>的情况下没有观察到。在没有细胞外<Ca^(2+)>的情况下，苯肾上腺素对这两种合成的刺激也被消除了。咖啡因使呼吸速率提高13%，表明咖啡因引起的尿素合成和糖异生增加的总ATP需求量为1.73 <微> mol/min/g湿重。这个值相当于由苯肾上腺素和咖啡因引起的总摄氧量增加所产生的总ATP的44%。在所有这些条件下，磷酸化电位恒定，为1.7 x <10^3> - 2.4 x <10^3> <M^(-1)>。葡萄糖和尿素的两种合成途径都有同样的途径获得细胞ATP供应，因为这两种合成都显示出非常相似的模式。咖啡因对线粒体内和细胞色素c氧化还原状态的影响更大。

Effects of caffeine on gluconeogenesis and ureagenesis of rat isolated hepatocyte were investigated in the presence of various hormonal agonists. Gluconeogenesis and urea synthesis from 4 mM glutamine were stimulated 1.7 fold and 1.9 fold (compared to control) by 10 <micro> M phenylephrine, respectively. The addition of caffeine at various concentrations with 10 <micro> M phenylephrine induced biphasic effects depending its concentration, i.e., stimulation ( <10^(-4)> - <10^(-3)> M), and inhibition (above 5 mM caffeine). Caffeine at 1 mM stimulated gluconeogenesis and urea synthesis 2.1 fold and 2.4 fold. Effects of caffeine were dependent upon the action of phenylephrine. Caffeine without phenylephrine did not affect both syntheses. Effects of caffeine required the presence of extracellular <Ca^(2+)> , and were not observed in the absence of extracellular <Ca^(2+)> . The stimulations of both syntheses by phenylephrine were also eliminated in the absence of extracellular <Ca^(2+)> .The respiratory rate was enhanced by 13 % by caffeine, indicating that the combined ATP requirement for the increase in urea synthesis and gluconeogenesis caused by caffeine is 1.73 <micro> mol/min/g wet weight. This value corresponded 44 % of total ATP produced by enhanced total oxygen uptake caused by phenylephrine and caffeine. The phosphorylation potentials were constant, 1.7 x <10^3> - 2.4 x <10^3> <M^(-1)> under all of these conditions. The two pathways of glucose and urea syntheses have equal access to the cellular ATP supply, since both syntheses showed very similar patterns. Intramitochondrial and cytochrome c redox state were more reduced by caffeine.