Effects of fatty acyl-coenzyme A esters on prostaglandin synthesis in rabbit kidney medulla microsomes.
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.
Fujimoto
Y
Y
Department of Hygienic Chemistry, Osaka University of Pharmaceutical Sciences, Japan.
Nakajima
T
T
Murakami
Y
Y
Takami
K
K
Nishida
H
H
Sakuma
S
S
Fujita
T
T
D000214:Acyl Coenzyme A / Q000494:pharmacology*; D000818:Animals; D016861:Cyclooxygenase Inhibitors; D015237:Dinoprost / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000037:antagonists & inhibitors; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000096:biosynthesis; D000071876:Prostaglandin-E Synthases; D011453:Prostaglandins / Q000096:biosynthesis*; D011817:Rabbits
D000214:Acyl Coenzyme A; D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D015237:Dinoprost; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone; D015230:Prostaglandin D2