Brass E P, Garrity M J
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262.
Biochim Biophys Acta. 1989 Feb 9;1010(2):233-6. doi: 10.1016/0167-4889(89)90166-3.
The hepatic level of prostaglandins will reflect the balance between synthesis of prostaglandins and their rapid catabolism via beta-oxidation by hepatocytes. In the present study we examined the effect of physiological fuel substrates on the breakdown and action of prostaglandin E2 (PGE2) in isolated rat hepatocytes. Palmitic acid (0.32 mM), a long-chain fatty acid, inhibited the rate of PGE2 breakdown (10(-7) M) by approx. 80%. As the palmitic acid concentration was increased from 0 to 0.8 mM, the percentage of PGE2 remaining in the incubation 5 min following prostaglandin addition was raised from approx. 10% to over 98%. Octanoic acid (0.8 mM) also inhibited PGE2 catabolism, while butyric acid (0.8 mM) and pyruvic acid (2.5 mM) were without effect. The inhibition of glucagon-stimulated glycogenolysis by PGE2 was increased in the presence of 0.6 mM palmitic acid, consistent with decreased PGE2 catabolism. These studies demonstrate that changes within the range of free fatty acid concentrations seen physiologically in vivo may dramatically alter PGE2 catabolism and, therefore, the effect of PGE2 to modulate hormonal action in the liver.
前列腺素的肝脏水平将反映前列腺素合成与其经肝细胞β-氧化的快速分解代谢之间的平衡。在本研究中，我们检测了生理性燃料底物对分离的大鼠肝细胞中前列腺素E2（PGE2）分解及作用的影响。棕榈酸（0.32 mM），一种长链脂肪酸，使PGE2（10⁻⁷ M）的分解速率降低了约80%。随着棕榈酸浓度从0增加到0.8 mM，添加前列腺素后5分钟孵育液中剩余PGE2的百分比从约10%提高到了98%以上。辛酸（0.8 mM）也抑制PGE2的分解代谢，而丁酸（0.8 mM）和丙酮酸（2.5 mM）则无此作用。在存在0.6 mM棕榈酸的情况下，PGE2对胰高血糖素刺激的糖原分解的抑制作用增强，这与PGE2分解代谢减少一致。这些研究表明，在体内生理状态下所见的游离脂肪酸浓度范围内的变化可能会显著改变PGE2的分解代谢，从而改变PGE2调节肝脏中激素作用的效果。
