CHANGES IN GASTRIC-MUCOSAL CONTENT OF ADENOSINE, XANTHINE AND HYPOXANTHINE INDUCED BY RESTRAINED WATER IMMERSION STRESS - ANTIULCER EFFECTS OF TETRAPRENYLACETONE

The purpose of this study was to clarify the involvement of adenine nucleotide metabolism and substrates of the xanthine-xanthine oxidase system as the source of oxygen free radicals in a rat model of restrained water immersion stress ulceration. The gastric mucosal concentrations of adenine-5'-triphosphate (ATP), adenine-5'-diphosphate (ADP), adenine-5'-monophosphate (AMP) and thiobarbituric-acid (TBA)-reactant substances were measured after 4, 8 and 12 h restrained water immersion stress. The gastric mucosal concentrations of the nucleoside adenosine, the purine bases xanthine and hypoxanthine, and the final metabolic product uric acid, were measured after 4 h of restrained water immersion stress. The concentrations of ATP diminished significantly after 4, 8 and 12 h of restrained water immersion stress. However, the observed stress-induced changes in ADP were not significant. AMP concentrations increased significantly after 4, 8 and 12 h of stress. The adenylate pool (ATP + ADP + AMP) dropped significantly from the prestress value after 4, 8 and 12 h of stress, and the concomitant energy charge (EC = ATP + 0.5 ADP/ATP + ADP + AMP) decreased significantly after 4 and 8 h of stress compared with the prestress value. Gastric mucosal concentrations of TBA-reactant substances displayed a significant increase after 4 h of stress, and remained unchanged after 8 and 12 h of stress from the level after 4 h. Four hours of restrained water immersion stress induced an increase in adenosine and uric acid concentrations and a decrease in the hypoxanthine concentration of the gastric mucosa. In addition, the protective effect of tetraprenylacetone (TPA) with respect to energy metabolism impairment and the production of active oxygen was investigated. Administration of TPA inhibited the ulcer formation, the reduction in energy charge values after 4 and 8 h of restrained water immersion stress and the increase in TBA-reactant substances after 4 h of restrained water immersion stress. TPA administration also inhibited the increase in adenosine and uric acid concentrations as well as the decrease in the hypoxanthine concentrations of the gastric mucosa caused by restrained water immersion stress. These results suggest that TPA exerted a cytoprotective action by virtue of its ability to counteract the adenine nucleotide metabolism and its action on the substrates of the xanthine-xanthine oxidase system.