Effects of eicosapentaenoic acid and its 15-hydroperoxy and 15-hydroxy derivatives on glucosamine synthetase activity in rabbit gastric mucosa.
The effects of eicosapentaenoic acid and its 15-hydroperoxy and 15-hydroxy adducts on the activity of glucosamine synthetase, the rate-limiting enzyme of mucus synthesis, in rabbit gastric antral mucosa were examined. 15-Hydroperoxy-eicosapentaenoic acid inhibited the glucosamine synthetase activity at concentrations of 10, 20 and 50 microM. The effect was concentration-dependent, and the concentration required for 50% inhibition was approximately 20 microM. Eicosapentaenoic acid and its 15-hydroxy adduct had no significant effect on the enzyme activity at the same concentration range. The experiment utilizing Fe2+ revealed that the inhibitory effect of 15-hydroperoxyeicosapentaenoic acid on the glucosamine synthetase activity is not due to hydroxy radical which is expected to be formed from the hydroperoxy adduct. These results suggest that 15-hydroperoxyeicosapentaenoic acid has the potential to reduce the synthesis of gastric mucus by inhibiting the glucosamine synthetase activity.
Department of Hygienic Chemistry, Osaka University of Pharmaceutical Sciences, Japan.
T
T
Fujita
S
S
Sakuma
N
N
Yamamoto
Y
Y
Fujimoto
D000818:Animals; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005296:Ferrous Compounds / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology*; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D011706:Pyloric Antrum; D011817:Rabbits
D005296:Ferrous Compounds; C059164:15-hydroxy-5,8,11,13,17-eicosapentaenoic acid; C044353:15-hydroperoxy-5,8,11,14,17-eicosapentaenoic acid; D015118:Eicosapentaenoic Acid; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)