Altin J G, Bygrave F L
Department of Biochemistry, Faculty of Science, Australian National University, Canberra.
Biochem J. 1988 Feb 1;249(3):677-85. doi: 10.1042/bj2490677.
The administration of prostaglandin F2 alpha (PGF2 alpha) and the thromboxane A2 analogue, ONO-11113, to rat livers perfused with media containing either 1.3 mM- or 10 microM-Ca2+ was followed by a stimulation of Ca2+ efflux, changes in O2 uptake and glucose output, and increase in portal pressure. The responses elicited by 5 microM-PGF2 alpha were similar to those induced by the alpha-adrenergic agonist phenylephrine. At both 1.3 mM and 10 microM extracellular Ca2+, PGF2 alpha induced Ca2+ efflux (70-90 nmol/g of liver), probably from the same source as that released by phenylephrine. Prostaglandin D2 (5 microM) and prostaglandin E2 (5 microM) also induced responses, but these were generally much smaller (less than 30%) than those induced by PGF2 alpha. Similarly to vasopressin and other Ca2+-mobilizing hormones, PGF2 alpha also interacted synergistically with glucagon (and cyclic AMP) in stimulating Ca2+ influx both in the perfused liver and in isolated hepatocytes. By comparison with phenylephrine and PGF2 alpha, ONO-11113 was much more potent in inducing vasoconstriction, and, at concentrations of 10-200 nM, induced a different pattern of changes in Ca2+ flux, respiration and glycogenolysis. There was first a rapid efflux of Ca2+ (45-60 nmol/g of liver), followed by a smaller Ca2+ influx, and a further release of Ca2+ (approx. 90 nmol/g of liver) when ONO-11113 was removed. Respiration was first stimulated but then markedly inhibited. At concentrations less than 5 nM, ONO-11113 induced a sustained stimulation of O2 uptake and a more prolonged efflux of Ca2+, with less Ca2+ efflux occurring upon the removal of the agent. Glycogenolysis followed a pattern which was similar to the Ca2+ response. Co-administration of glucagon did not potentiate Ca2+ influx by ONO-11113, but the action of ONO-11113 was inhibited (50%) by a few minutes' prior administration of 10 nM-vasopressin. The vasoconstrictive action of ONO-11113 was synergistically potentiated by the co-administration of phenylephrine. Since the actions of arachidonic acid, platelet-activating factor and lysophosphatidylcholine in liver were recently found to be cyclo-oxygenase-sensitive, the results provide strong evidence that at least PGF2 alpha and thromboxane A2 may be involved in mediating the action of these agents.
向灌注含有1.3 mM或10 microM钙离子的培养基的大鼠肝脏中注射前列腺素F2α（PGF2α）和血栓素A2类似物ONO - 11113后，会刺激钙离子外流、氧气摄取和葡萄糖输出发生变化，并使门静脉压力升高。5 microM - PGF2α引发的反应与α - 肾上腺素能激动剂去氧肾上腺素诱导的反应相似。在细胞外钙离子浓度为1.3 mM和10 microM时，PGF2α均诱导钙离子外流（70 - 90 nmol/g肝脏），其来源可能与去氧肾上腺素释放钙离子的来源相同。前列腺素D2（5 microM）和前列腺素E2（5 microM）也能诱导反应，但这些反应通常比PGF2α诱导的反应小得多（小于30%）。与血管加压素和其他动员钙离子的激素类似，PGF2α在灌注肝脏和分离的肝细胞中刺激钙离子内流时，也与胰高血糖素（和环磷酸腺苷）协同作用。与去氧肾上腺素和PGF2α相比，ONO - 11113诱导血管收缩的作用更强，在浓度为10 - 200 nM时，会诱导钙离子通量、呼吸和糖原分解发生不同模式的变化。首先是钙离子快速外流（45 - 60 nmol/g肝脏），随后是较小的钙离子内流，当去除ONO - 11113时，会进一步释放钙离子（约90 nmol/g肝脏）。呼吸首先受到刺激，但随后明显受到抑制。在浓度低于5 nM时，ONO - 11113诱导氧气摄取持续增加和钙离子外流时间延长，去除该药物后钙离子外流减少。糖原分解的模式与钙离子反应相似。同时给予胰高血糖素不会增强ONO - 11113诱导的钙离子内流，但在提前几分钟给予10 nM血管加压素后，ONO - 11113的作用会被抑制（50%）。同时给予去氧肾上腺素会协同增强ONO - 11113的血管收缩作用。由于最近发现花生四烯酸、血小板活化因子和溶血磷脂酰胆碱在肝脏中的作用对环氧化酶敏感，这些结果提供了有力证据，表明至少PGF2α和血栓素A2可能参与介导这些物质的作用。
