Role of Protein Kinase C in the Regulation of Hepatic Flow and Metabolism in the Perfused rat liver

蛋白激酶C（PKC）被认为参与肝脏血流和代谢的调节。PKC调节对肝流量和碳水化合物代谢的影响进行了研究，在大鼠肝脏，这是从喂养或禁食大鼠分离，并通过门静脉灌注在恒定的压力为12千帕。佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）和4 β-佛波醇双癸酸酯，PKC的活性佛波醇酯，减少肝流量和氧消耗，并增加净乳酸产生。PMA增强了进食大鼠的净葡萄糖生成。4 α-佛波醇双癸酸酯是一种对PKC无活性的佛波醇酯，对肝流量和耗氧量的影响可忽略不计。PMA的影响增强了培养基中的钙和葡萄糖浓度的增加。活性PKC抑制剂（staurosporine和H-7）减弱PMA的作用，而非活性PKC抑制剂（HA-1004）不减弱PMA的作用。用氯化钆预处理大鼠，Kupffer细胞的抑制剂也减弱PMA的作用。这些结果表明，PKC，特别是Kupffer细胞中的PKC，在调节肝流量和代谢中起重要作用，并且PKC的激活作用受门静脉葡萄糖和钙浓度的影响。挥发性麻醉剂异氟烷和氟烷减弱PMA引起的肝流量的改变，氧消耗和乳酸盐产生。

Protein Kinase C (PKC) has been suggested to be involved in the regulation of hepatic flow and metabolism. The effects of PKC modulation on hepatic flow and carbohydrate metabolism were studied in the rat liver, which was isolated from fed or fasted rats, and perfused through the portal vein at a constant pressure of 12 kPa. Phorbol 12-myristate 13-acetate (PMA) and 4beta-phorbol didecanoate, active phorbol esters for PKC,decreased the hepatic flow and oxygen consumption, and increased net lactate production. PMA enhanced net glucose production in fed rats. 4alpha-phorbol didecanoate, an inactive phorbol ester for PKC,had negligible influences on the hepatic flow and oxygen consumption. The effects of PMA was augmented by the increases in calcium and glucose concentrations in the medium. The effects of PMA were attenuated by ative PKC inhibitors (staurosporine and H-7) but not by an inactive PKC inhibitor (HA-1004). Pretreatment of rats with gadolinium chloride, an incativator of Kupffer cells also inhibitted the effects of PMA.These results suggest that PKC,particularly in Kupffer cells, has an important role in the regulation of hepatic flow and metabolism, and that effects of PKC activation is modified by the portal glucose and calcium concentrations.Volatile anesthetics, isoflurane and halothane, attenuated the PMA-induced alterations in hepatic flow, oxygen consumption, and lactate production.