Free Content Circadian rhythm of melatonin and prostaglandin in modulation of stress-induced gastric mucosal lesions in rats

Authors: Kato, K.1; Murai, I.2; Asai, S.3; Takahashi, Y.3; Nagata, T.3; Komuro, S.1; Mizuno, S.1; Iwasaki, A.1; Ishikawa, K.4; Arakawa, Y.1

Source: Alimentary Pharmacology & Therapeutics, Volume 16, Supplement 2, April 2002 , pp. 29-34(6)

Publisher: Blackwell Publishing

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Abstract:

Background:

We previously demonstrated the circadian variation of water-immersion restraint stress (WRS)-induced gastric mucosal lesions in rats. Aim:

To investigate the roles of melatonin and prostaglandin in the gastric mucosa in circadian modulation of WRS. Methods:

Fasted rats were subjected to 4-h WRS during both the diurnal and nocturnal phases of a light/dark cycle. Mucosal lesions, serum melatonin concentrations, mucosal generation of prostaglandin E2 (PGE2) and mucosal gene expressions of cyclooxygenase (COX)-1 and -2 were evaluated. Results:

Lesion area after 4-h stress during the dark phase was significantly smaller than that in light-phase controls. Serum melatonin concentration in control rats during the light phase was significantly increased 4 h after WRS, but PGE2 generation was decreased by 48% as compared to that in intact mucosa before stress. In the dark phase, melatonin concentration after 4-h WRS was significantly depressed as compared with the control level at the corresponding time. PGE2 concentrations after 4-h WRS in the dark phase were not decreased compared with the control level at the corresponding time, although PGE2 level was significantly lower than that in light-phase controls. Expression of COX-1 and COX-2 mRNA was detected after exposure to stress in both the light and dark phases. Conclusion:

These results suggest that circadian rhythm has an important role in the formation of stress-induced gastric mucosal lesions in rats. The circadian rhythm of melatonin responses and PGE2 generation may contribute to nocturnal/diurnal rhythmicity of gastric mucosal defences between day and night.

Document Type: Research article

DOI: 10.1046/j.1365-2036.16.s2.11.x

Affiliations: 1: Third Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan, 2: Department of Biochemistry, Nihon University School of Medicine, Tokyo, Japan, 3: Advanced Medical Research Center, Nihon University School of Medicine, Tokyo, Japan, 4: Department of Pharmacology, Nihon University School of Medicine, Tokyo, Japan

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