ROLES OF DIURNAL RHYTHM AND PINEAL HORMONE MELATONIN, IN THE GASTRIC MUCOSA PROTECTING MECHANISM

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We investigated the mechanism by which melatonin (ML) protected the gastric mucosa and the relation to diurnal rhythm. We found that ML, which is secreted by the pineal body in response to stress, protects the gastric mucosa. We also found that ML showed not only peripheral but also central gastric mucosa-protecting actions. It was suggested that these actions are mediated by a brain ML receptor, Ib. With respect to the relation to diurnal rhythm, water-immersion restriction stress was given to rats during the light/dark periods. In the group with stress during the dark period, gastric lesions were significantly inhibited than in the group with stress during the light period. Gastric mucosa prostaglandin (PG)E_2 production reduced after stress loading during the light period. However, during the dark period, reduction was inhibited compared to that in the control group. Furthermore, the concentration of ML during the dark period was significantly higher than that during the light perio … More d in the control group before stress loading, suggesting the association with inhibition of gastric lesions. The expression of COX-2 mRNA, which has been reported to play an important role in the repair process of digestive tract mucosal injury, was detected during both the light and dark periods after stress loading. Regardless of the number of lesions, COX-2 mRNA may appear prior to repair of gastric mucosal lesions after stress loading. This finding may reflect inhibition of gastric mucosa PGE_2 production after stress loading. In the group in which the pineal body was extirpated, gastric mucosal lesions exacerbated after stress loading during the dark period. However, exacerbation was significantly inhibited by intracisternal pretreatment with ML. These findings suggest that diurnal rhythm markedly influences the development of stress-induced gastric lesions, ML/PGE_2 production, and COX-2 mRNA expression. Furthermore, blood ML and urinary ML metabolite levels were measured in healthy volunteers and patients with gastric cancer or digestive ulcer, and we confirmed that urinary ML metabolite levels were decreased in patients with advanced gastric cancer. In the future, the usefulness of these parameters as biochemical markers should be investigated. Less