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

蛋白激酶 C 在灌注大鼠肝脏中肝血流和代谢调节中的作用

基本信息

批准号：
05671249
负责人：
INABA Hideo
金额：
$ 1.41万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671249/
关键词：
Protein Kinase C Phorbol esters H-7 HA-1004 Ioslated, perfused liver Kupffer cells glucose gadolinium chloride プロテインキナーゼC phorbol myristate acetate Kupffer cell HA1004 staurosporine 摘出肝カルシウム

项目摘要

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.

蛋白激酶 C (PKC) 被认为参与肝血流和代谢的调节。在大鼠肝脏中研究了 PKC 调节对肝流量和碳水化合物代谢的影响，该肝脏从进食或禁食的大鼠中分离出来，并在 12 kPa 的恒定压力下通过门静脉灌注。佛波醇 12-肉豆蔻酸酯 13-乙酸酯 (PMA) 和 4β-佛波醇二癸酸酯是 PKC 的活性佛波醇酯，可减少肝流量和耗氧量，并增加净乳酸产量。 PMA 增强了喂食大鼠的净葡萄糖产量。 4α-佛波醇二癸酸酯是一种对 PKC 无活性的佛波酯，对肝流量和耗氧量的影响可以忽略不计。 PMA 的效果因培养基中钙和葡萄糖浓度的增加而增强。 PMA 的作用可被活性 PKC 抑制剂（星形孢菌素和 H-7）减弱，但不会被非活性 PKC 抑制剂（HA-1004）减弱。用氯化钆（Kupffer 细胞的激活剂）预处理大鼠也抑制了 PMA 的作用。这些结果表明 PKC，特别是在 Kupffer 细胞中，在肝血流和代谢的调节中具有重要作用，并且 PKC 激活的效果受到门静脉葡萄糖和钙浓度的影响。挥发性麻醉剂、异氟烷和氟烷可减弱 PMA 引起的肝流量、耗氧量和乳酸生成的变化。