Björnsson O G, Sparks J D, Sparks C E, Gibbons G F
Metabolic Research Laboratory, Radcliffe Infirmary, Oxford, United Kingdom.
J Lipid Res. 1992 Jul;33(7):1017-27.
In primary cultures of rat hepatocytes, prostaglandin E2 and prostaglandin D2 (PGE2 and PGD2) inhibited the secretion of very low density lipoprotein (VLDL)-associated apoB, triacylglycerol, and cholesterol. These effects were concentration-dependent and remained apparent for at least 3 days of culture without an effect on the apoB/triacylglycerol ratio of the secreted VLDL. Prostaglandins had no effect on the overall synthesis of triacylglycerol but triacylglycerol accumulated within the cells, without intracellular accumulation of apoB. PGE2, when added to the medium together with glucagon, increased the inhibition of VLDL secretion, compared to that observed with glucagon alone. However, PGE2 did not increase the stimulatory effect of glucagon on ketogenesis. Unlike glucagon, the prostaglandins did not inhibit fatty acid synthesis nor did they stimulate ketogenesis or production of cAMP. Thus, of all the parameters of hepatic lipid metabolism studied, PGE2 and PGD2 selectively affected VLDL. Selective inhibition of VLDL secretion was also observed with the calcium antagonist verapamil. The divalent cation ionophore A23187 also inhibited VLDL release but, in contrast, also inhibited fatty acid and cholesterol synthesis. The results suggest that VLDL secretion is modulated at some optimal cell calcium concentration that may be mediated selectively by agents such as prostaglandins.
在大鼠肝细胞原代培养物中，前列腺素E2和前列腺素D2（PGE2和PGD2）抑制极低密度脂蛋白（VLDL）相关载脂蛋白B、三酰甘油和胆固醇的分泌。这些作用呈浓度依赖性，并且在至少3天的培养过程中仍然明显，而对分泌的VLDL的载脂蛋白B/三酰甘油比值没有影响。前列腺素对三酰甘油的总体合成没有影响，但三酰甘油在细胞内蓄积，而载脂蛋白B没有在细胞内蓄积。与单独使用胰高血糖素相比，当PGE2与胰高血糖素一起添加到培养基中时，对VLDL分泌的抑制作用增强。然而，PGE2并没有增强胰高血糖素对生酮作用的刺激效果。与胰高血糖素不同，前列腺素既不抑制脂肪酸合成，也不刺激生酮作用或cAMP的产生。因此，在所有研究的肝脏脂质代谢参数中，PGE2和PGD2选择性地影响VLDL。钙拮抗剂维拉帕米也观察到对VLDL分泌的选择性抑制。二价阳离子载体A23187也抑制VLDL释放，但相反，它也抑制脂肪酸和胆固醇合成。结果表明，VLDL分泌在某个最佳细胞钙浓度下受到调节，这可能由前列腺素等物质选择性介导。
