Digestive Diseases and Sciences

, Volume 52, Issue 2, pp 478–487 | Cite as

Preconditioning Stress Prevents Cold Restraint Stress-Induced Gastric Lesions in Rats: Roles of COX-1, COX-2, and PLA2

  • Akiko Tanaka
  • Ryo Hatazawa
  • Yuka Takahira
  • Nahoko Izumi
  • Ludmila Filaretova
  • Koji Takeuchi
Original Article


We investigated the protective effect of mild stress on gastric lesions induced by cold-restraint stress, especially concerning prostaglandins (PGs)/cyclo-oxygenase (COX) isozymes. Rats were exposed to severe stress (cold-restraint stress at 10°C for 6 hr) or mild stress (cold-restraint stress at 10°C for 30 min and kept at room temperature for 60 min) followed by severe stress. Severe stress induced gastric lesions, with a concomitant decrease in body temperature (BT). The ulcerogenic response was inhibited by atropine but worsened by indomethacin and SC-560 but not rofecoxib, although none of these agents had any effect on the change in BT. Mild stress suppressed the gastric ulceration and the decrease in BT induced by severe stress, and these effects were reversed by both COX-1 and COX-2 inhibitors. The expression of COX-2 in the stomach was up-regulated from 4 hr after severe stress and this response was slightly expedited by mild stress. COX-2 was also expressed in the hypothalamus under normal and stressed conditions. Quinacrine (phospholipase A2 inhibitor) attenuated the protective effect of mild stress on the ulceration and decrease in BT caused by severe stress. TA-0910 (TRH analogue) at a low dose also prevented the gastric ulceration and the decrease in BT induced by severe stress. These results suggest that mild stress protects against cold-restraint stress-induced gastric ulceration, and the effect is peripherally and centrally mediated by PGs derived from both COX-1 and COX-2 through the activation of phospholipase A2. TRH may also be involved in the protective effect of mild stress, probably through regulation of the thermogenic system.


Cold-restraint stress Preconditioning stress Gastric lesion COX isozyme Selective COX inhibitor Rat 



This research was supported in part by the Kyoto Pharmaceutical University’s “21st Century COE” program and the “Open Research” Program of the Ministry of Education, Science and Culture of Japan.


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Copyright information

© Springer Science+Business Media, Inc. 2007

Authors and Affiliations

  • Akiko Tanaka
    • 1
  • Ryo Hatazawa
    • 1
  • Yuka Takahira
    • 1
  • Nahoko Izumi
    • 1
  • Ludmila Filaretova
    • 1
  • Koji Takeuchi
    • 1
  1. 1.Department of Pharmacology and Experimental TherapeuticsKyoto Pharmaceutical UniversityKyotoJapan

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