dinoprost and 13-hydroperoxy-9-11-octadecadienoic-acid

The effect of 13-hydroperoxyoctadecadienoic acid (13-HPODE), a hydroperoxy adduct of linoleic acid (LA), on the activities of prostaglandin (PG) synthesizing and catabolizing enzymes in rabbit gastric antral mucosa was examined. 13-HPODE had no effect on the synthesis of PGE2, PGF2 alpha and PGD2 from exogenous arachidonic acid in the microsomal fraction of the gastric mucosa at concentrations ranging from 5-20 microM. On the other hand, at 1-10 microM, it inhibited the activity of 15-hydroxy PG dehydrogenase (PGDH), which catalyzes the initial step of catabolism of PGs, in a dose-dependent manner. The concentration required for 50% inhibition was approximately 1 microM. Experiments utilizing LA, 13-hydroperoxyoctadecadienoic acid and Fe2+ indicated the requirement of the hydroperoxy moiety for the inhibitory effect of 13-HPODE on the PGDH activity. These results suggest that 13-HPODE has the potential to increase the levels of biologically active PGs in gastric mucosa by preventing their inactivation and may have functional effects within the stomach.

Topics: Animals; Arachidonic Acid; Chromatography, High Pressure Liquid; Cytosol; Dinoprost; Dinoprostone; Gastric Mucosa; Hydroxyprostaglandin Dehydrogenases; Linoleic Acids; Lipid Peroxides; Male; Microsomes; Prostaglandin D2; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Pyloric Antrum; Rabbits

The effect of 13-hydroperoxyoctadecadienoic acid (13-HPODE) on the synthesis of prostaglandins (PGs) was examined in rabbit kidney medulla microsomes. Medulla microsomes were incubated with arachidonic acid in 0.1 M-Tris/HCl buffer (pH 8.0) containing reduced glutathione and hydroquinone and the PGE2, PGF2a and PGD2 formed were measured by high-pressure liquid chromatography using 9-anthryldiazomethane for derivatization. Under our incubation conditions rabbit kidney medulla was found to produce mainly PGE2. The addition of 13-HPODE inhibited the production of all three PGs to a similar extent. 13-Hydroxyoctadecadienoic acid did not suppress the formation of PGs, indicating the requirement 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 fatty acid-derived hydroperoxide in PG synthesis by kidney medulla. We conclude that 13-HPODE is an inhibitor of renomedullary cyclooxygenase and may have functional effects within the kidney.

Topics: Animals; Arachidonic Acid; Dinoprost; Dinoprostone; Kidney Medulla; Linoleic Acids; Lipid Peroxides; Male; Microsomes; Prostaglandin D2; Rabbits