Inhibition of 15-hydroxy prostaglandin dehydrogenase activity in rabbit gastric antral mucosa by 13-hydroperoxyoctadecadienoic 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.
Sakuma
S
S
Department of Hygienic Chemistry, Osaka University of Pharmaceutical Sciences, Japan.
Fujimoto
Y
Y
Miyata
Y
Y
Yamane
K
K
Nishida
H
H
Fujita
T
T
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000201:enzymology; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology; D006911:Hydroxyprostaglandin Dehydrogenases / Q000037:antagonists & inhibitors*; D008041:Linoleic Acids / Q000494:pharmacology*; D008054:Lipid Peroxides; D008297:Male; D008861:Microsomes / Q000201:enzymology; D015230:Prostaglandin D2 / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D011706:Pyloric Antrum / Q000187:drug effects* / Q000201:enzymology; D011817:Rabbits
D008041:Linoleic Acids; D008054:Lipid Peroxides; D011453:Prostaglandins; C038649:13-hydroperoxy-9,11-octadecadienoic acid; D016718:Arachidonic Acid; C026346:15-ketoprostaglandin E2; C025087:15-keto-13,14-dihydroprostaglandin E2; D015237:Dinoprost; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D015230:Prostaglandin D2