Fujimoto Y, Nakajima T, Murakami Y, Takami K, Nishida H, Sakuma S, Fujita T
Department of Hygienic Chemistry, Osaka University of Pharmaceutical Sciences, Japan.
Prostaglandins Leukot Essent Fatty Acids. 1992 Dec;47(4):265-8. doi: 10.1016/0952-3278(92)90196-p.
The effects of fatty acyl-coenzyme A (CoA) esters (palmitoyl-, stearoyl-, oleoyl-, linoleoyl- and arachidonoyl-CoA) on the synthesis of prostaglandins (PGs) in rabbit kidney medulla microsomes were examined. Medulla microsomes were incubated with arachidonic acid in 0.1 M-Tris/HCl buffer (pH 8.0) containing reduced glutathione and hydroquinone and the formed PGE2, PGF2 alpha and PGD2 were measured by high-pressure liquid chromatography using 9-anthryldiazomethane for derivatization. Under our incubation conditions rabbit kidney medulla was found to produce PGE2 mainly. The addition of fatty acyl-CoA esters inhibited total PG formation (the sum of PGE2, PGF2 alpha and PGD2) in a dose-dependent manner. Palmitoyl-, stearoyl- and oleoyl-CoA were about 10 times more potent than linoleoyl- and arachidonoyl-CoA as inhibitors of total PG formation. Linoleic acid was slightly more effective than linoleoyl-CoA, while palmitic acid had no influence on PG formation. All the fatty acyl-CoA esters inhibited the formation of PGE2. Simultaneously, the production of PGF2 alpha and PGD2 was increased. These results suggest that the CoA derivatives of palmitic, stearic and oleic acids have the potential to modulate PGE2, PGF2 alpha and PGD2 synthesis by affecting the activities of both-cyclooxygenase and endoperoxide E2 isomerase.
研究了脂肪酰辅酶A(CoA)酯(棕榈酰辅酶A、硬脂酰辅酶A、油酰辅酶A、亚油酰辅酶A和花生四烯酰辅酶A)对兔肾髓质微粒体中前列腺素(PGs)合成的影响。将髓质微粒体与花生四烯酸在含有还原型谷胱甘肽和对苯二酚的0.1M Tris/HCl缓冲液(pH 8.0)中孵育,使用9-蒽重氮甲烷进行衍生化,通过高压液相色谱法测定生成的PGE2、PGF2α和PGD2。在我们的孵育条件下,发现兔肾髓质主要产生PGE2。脂肪酰辅酶A酯的添加以剂量依赖性方式抑制总PG形成(PGE2、PGF2α和PGD2的总和)。棕榈酰辅酶A、硬脂酰辅酶A和油酰辅酶A作为总PG形成抑制剂的效力比亚油酰辅酶A和花生四烯酰辅酶A高约10倍。亚油酸比亚油酰辅酶A稍有效,而棕榈酸对PG形成没有影响。所有脂肪酰辅酶A酯均抑制PGE2的形成。同时,PGF2α和PGD2的产生增加。这些结果表明,棕榈酸、硬脂酸和油酸的辅酶A衍生物有可能通过影响环氧化酶和内过氧化物E2异构酶的活性来调节PGE2、PGF2α和PGD2的合成。