EFFECT OF 13-HYDROPEROXYOCTADECADIENOIC ACID ON PROSTAGLANDIN SYNTHESIS IN RABBIT KIDNEY MEDULLA MICROSOMES

The effect of 13-hydroperoxyoctadecadienoic acid (13-HPODE) on the syn thesis of prostaglandins (PGs) was examined in rabbit kidney medulla m icrosomes. Medulla microsomes were incubated with arachidonic acid in 0.1 M-Tris/HCl buffer (pH 8.0) containing reduced glutathione and hydr oquinone and the PGE(2), PGF(2a) and PGD(2) formed were measured by hi gh-pressure liquid chromatography using 9-anthryldiazomethane for deri vatization. Under our incubation conditions rabbit kidney medulla was found to produce mainly PGE(2). The addition of 13-HPODE inhibited the production of all three PGs to a similar extent. 13-Hydroxyoctadecadi enoic acid did not suppress the formation of PGs, indicating the requi rement of the hydroperoxy moiety for the inhibitory effect of 13-HPODE on PG formation. Experiments utilizing the native fatty acid linoleic acid and tert-butyl hydroperoxide suggested the importance of the fat ty acid-derived hydroperoxide in PG synthesis by kidney medulla. We co nclude that 13-HPODE is an inhibitor of renomedullary cyclooxygenase a nd may have functional effects within the kidney.