Circadian rhythm of melatonin and prostaglandin in modulation of stress-induced gastric mucosal lesions in rats.
BACKGROUND
We previously demonstrated the circadian variation of water-immersion restraint stress (WRS)-induced gastric mucosal lesions in rats.


OBJECTIVE
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.


CONCLUSIONS
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.
Kato
K
K
Third Department of Internal Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan. kimitosi@med.nihon-u.ac.jp
Murai
I
I
Asai
S
S
Takahashi
Y
Y
Nagata
T
T
Komuro
S
S
Mizuno
S
S
Iwasaki
A
A
Ishikawa
K
K
Arakawa
Y
Y
D000818:Animals; D002940:Circadian Rhythm; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008550:Melatonin / Q000097:blood*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D013312:Stress, Physiological / Q000150:complications
D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D008550:Melatonin; D015232:Dinoprostone