Iwai M, Gardemann A, Püschel G, Jungermann K
Institut für Biochemie, Fachbereich Medizin, Georg-August-Universität, Göttingen, Federal Republic of Germany.
Eur J Biochem. 1988 Jul 15;175(1):45-50. doi: 10.1111/j.1432-1033.1988.tb14164.x.
In isolated rat liver perfused at constant pressure perivascular nerve stimulation caused an increase of glucose and lactate output and a reduction of perfusion flow. The metabolic and hemodynamic nerve effects could be inhibited by inhibitors of prostanoid synthesis, which led to the suggestion that the effects of nerve stimulation were, at least partially, mediated by prostanoids [Iwai, M. & Jungermann, K. (1987) FEBS Lett. 221, 155-160]. This suggestion is corroborated by the present study. 1. Prostaglandin D2, E2 and F2 alpha as well as the thromboxane A2 analogue U46619 enhanced glucose and lactate release and lowered perfusion flow similar to nerve stimulation. 2. The extents, the kinetics and the concentration dependencies of the metabolic and hemodynamic actions of the various prostanoids were different. Prostaglandin F2 alpha and D2 caused relatively stronger changes of metabolism, while prostaglandin E2 and U46619 had stronger effects on hemodynamics. Prostaglandin F2 alpha elicited greater maximal alterations than D2 with similar half-maximally effective concentrations. Prostaglandin F2 alpha mimicked the nerve actions on both metabolism and hemodynamics best with respect to the relative extents and the kinetics of the alterations. 3. The hemodynamic effects of prostaglandin F2 alpha could be prevented completely by the calcium antagonist nifedipine without impairing the metabolic actions of the prostanoid. Apparently, prostaglandin F2 alpha influenced metabolism directly rather than indirectly via hemodynamic changes. The present results, together with the previously described effects of prostanoid synthesis inhibitors, suggest that prostanoids, probably prostaglandin F2 alpha and/or D2, could be involved in the actions of sympathetic hepatic nerves on liver carbohydrate metabolism. Since prostanoids are synthesized only in non-parenchymal cells, nervous control of metabolism appears to depend on complex intra-organ cell-cell interactions between the nerve, non-parenchymal and parenchymal cells.
在恒压灌注的离体大鼠肝脏中，血管周围神经刺激可导致葡萄糖和乳酸输出增加以及灌注流量减少。前列腺素合成抑制剂可抑制神经的代谢和血流动力学效应，这表明神经刺激的效应至少部分是由前列腺素介导的[岩井，M. & 容格曼，K.（1987年）《欧洲生物化学会联合会快报》221，155 - 160]。本研究证实了这一观点。1. 前列腺素D2、E2和F2α以及血栓素A2类似物U46619可增强葡萄糖和乳酸释放，并降低灌注流量，类似于神经刺激。2. 各种前列腺素的代谢和血流动力学作用的程度、动力学和浓度依赖性各不相同。前列腺素F2α和D2引起相对较强的代谢变化，而前列腺素E2和U46619对血流动力学有更强的影响。在相似的半数最大有效浓度下，前列腺素F2α引起的最大变化比D2更大。就变化的相对程度和动力学而言，前列腺素F2α在代谢和血流动力学方面对神经作用的模拟效果最佳。3. 钙拮抗剂硝苯地平可完全阻止前列腺素F2α的血流动力学效应，而不损害该前列腺素的代谢作用。显然，前列腺素F2α直接影响代谢，而非通过血流动力学变化间接影响。目前的结果，连同先前描述的前列腺素合成抑制剂的作用，表明前列腺素，可能是前列腺素F2α和/或D2，可能参与交感肝神经对肝脏碳水化合物代谢的作用。由于前列腺素仅在非实质细胞中合成，代谢的神经控制似乎取决于神经、非实质细胞和实质细胞之间复杂的器官内细胞间相互作用。
