Püschel G P, Jungermann K
Institut für Biochemie, Fachbereich Medizin, Georg-August-Universität Göttingen, Federal Republic of Germany.
Eur J Biochem. 1988 Jul 15;175(1):187-91. doi: 10.1111/j.1432-1033.1988.tb14182.x.
In the isolated rat liver perfused in situ, stimulation of the nerve bundles around the hepatic artery and portal vein caused an increase of glucose and lactate output and a reduction of perfusion flow. These changes could be inhibited completely by alpha-receptor blockers. The possible involvement of inositol phosphates in the intracellular signal transmission was studied. 1. In cell-suspension experiments, which were performed as a positive control, noradrenaline caused an increase in glucose output and, in the presence of 10 mM LiCl, a dose-dependent and time-dependent increase of inositol mono, bis and trisphosphate. 2. In the perfused rat liver 1 microM noradrenaline caused an increase of glucose and lactate output and in the presence of 10 mM LiCl a time-dependent increase of inositol mono, bis and trisphosphate that was comparable to that observed in cell suspensions. 3. In the perfused rat liver stimulation of the nerve bundles around the portal vein and hepatic artery caused a similar increase in glucose and lactate output to that produced by noradrenaline, but in the presence of 10 mM LiCl there was a smaller increase of inositol monophosphate and no increase of inositol bis and trisphosphate. These findings are in line with the proposal that circulating noradrenaline reaches every hepatocyte, causing a clear overall increase of inositol phosphate formation and thus calcium release from the endoplasmic reticulum, while the hepatic nerves reach only a few cells causing there a small local change of inositol phosphate metabolism and thence a propagation of the signal via gap junctions.
在原位灌注的离体大鼠肝脏中，刺激肝动脉和门静脉周围的神经束会导致葡萄糖和乳酸输出增加以及灌注流量减少。这些变化可被α受体阻滞剂完全抑制。研究了肌醇磷酸酯在细胞内信号转导中的可能作用。1. 在作为阳性对照进行的细胞悬浮实验中，去甲肾上腺素导致葡萄糖输出增加，并且在存在10 mM LiCl的情况下，肌醇一磷酸、二磷酸和三磷酸呈剂量依赖性和时间依赖性增加。2. 在灌注的大鼠肝脏中，1 μM去甲肾上腺素导致葡萄糖和乳酸输出增加，并且在存在10 mM LiCl的情况下，肌醇一磷酸、二磷酸和三磷酸呈时间依赖性增加，这与在细胞悬浮液中观察到的情况相当。3. 在灌注的大鼠肝脏中，刺激门静脉和肝动脉周围的神经束导致葡萄糖和乳酸输出的增加与去甲肾上腺素引起的增加相似，但在存在10 mM LiCl的情况下，肌醇单磷酸的增加较小，肌醇二磷酸和三磷酸没有增加。这些发现符合以下观点：循环中的去甲肾上腺素到达每个肝细胞，导致肌醇磷酸酯形成明显总体增加，从而使内质网释放钙，而肝神经仅到达少数细胞，在那里引起肌醇磷酸酯代谢的局部小变化，并由此通过间隙连接传播信号。
