Effects of fatty acyl-coenzyme A esters on prostaglandin synthesis in rabbit kidney medulla microsomes

Abstract

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 PGE 2, PGF 2α and PGD 2 were measured by high-pressure liquid chromatography using 9-anthryldiazomethane for derivatization. Under our incubation conditions rabbit kidney medulla was found to produce PGE 2 mainly. The addition of fatty acyl-CoA esters inhibited total PG formation (the sum of PGE 2, PGF 2α and PGD 2) 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 PGE 2. Simultaneously, the production of PGF 2α and PGD 2 was increased. These results suggest that the CoA derivatives of palmitic, stearic and oleic acids have the potential to modulate PGE 2, PGF 2α and PGD 2 synthesis by affecting the activities of bothcyclooxygenase and endoperoxide E 2 isomerase.