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.