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

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Abstract

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.

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References

  1. Senay EC, Levine RJ (1967) Synergism between cold and restraint for rapid production of stress ulcers in rats. Proc Soc Exp Biol Med 124:1221–1223

    PubMed  CAS  Google Scholar 

  2. Niida H, Takeuchi K, Okabe S (1991) Role of thyrotropin–releasing hormone in acid secretory response induced by lowering of body temperature in the rat. Eur J Pharmacol 198:137–142

    Article  PubMed  CAS  Google Scholar 

  3. Niida H, Takeuchi K, Ueshima K, Okabe S (1991) Vagally–mediated acid hypersecretion and lesion formation under hypothermic conditions in the rat. Dig Dis Sci 36:441–448

    Article  PubMed  CAS  Google Scholar 

  4. Jobin M, Ferland L, Cote J, Labrie F (1975) Effect of exposure to cold on hypothalamic TRH activity and plasma levels of TSH and prolactin in the rat. Neuroendocrinology 18:204–212

    PubMed  CAS  Google Scholar 

  5. Hernadez DE, Hennes L, Emerick SG (1987) Inhibitiion of gastric acid secretion by immunoreutralization of endogenous brain thyrotropin–releasing hormone. Brain Res 401:381–384

    Article  Google Scholar 

  6. Basso N, Bagarani M, Pekary AE, Genco A, Materia A (1998) Role of thyrotropin-releasing hormone in stress ulcer formation in the rat. Dig Dis Sci 33:819–823

    Article  Google Scholar 

  7. Konturek PK, Brzozowski T, Konturek SJ, Dembinski A (1990) Role of epidermal growth factor, prostaglandin, and sulfhydryls in stress-induced gastric lesions. Gastroenterology 99:1607–1615

    PubMed  CAS  Google Scholar 

  8. Takeuchi K, Ukawa H, Konaka A, Kitamura M, Sugawa Y (1998) Effect of nitric oxide-releasing aspirin on gastric functional and ulcerogenic responses in rats:Comparison with aspirin. J Pharmacol Exp Ther 286:115–121

    PubMed  CAS  Google Scholar 

  9. Ukawa H, Yamakuni H, Kato S, Takeuchi K (1998) Effects of cyclooxygenase-2 selective and nitric oxide-releasing nonsteroidal anti-inflammatory drugs on gastric ulcerogenic and healing responses in experimental animals. Dig Dis Sci 43:2003–2011

    Article  PubMed  CAS  Google Scholar 

  10. Takeuchi K, Suzuki K, Araki H, Mizoguchi H, Sugamoto S, Umdeda M (1999) Roles of endogenous prostaglandins and nitric oxide in gastroduodenal ulcerogenic responses induced in rats by hypothermic stress. J Physiol Paris 93:423–431

    Article  PubMed  CAS  Google Scholar 

  11. Takeuchi K, Tanaka A, Suzuki K, Mizoguchi H, Araki H (2001) Gastrointestinal sparing anti-inflammatory drugs: Effects on ulcerogenic and healing responses. Curr Pharm Design 7:49–71

    Article  CAS  Google Scholar 

  12. Wallace JL, Track NS, Cohen MM (1983) Chronic mild restraint protects the rat gastric mucosa from injury by ethanol or cold restraint. Gastroenterology 85:370–375

    PubMed  CAS  Google Scholar 

  13. Wallace JL, Cohen MM (1984) Gastric mucosal protection with chronic mild restraint: Role of endogenous prostaglandins. Am J Physiol 247:G127–G132

    PubMed  CAS  Google Scholar 

  14. Brzozowski T, Konturek PC, Konturek SJ, Drozdowicz D, Pajdo R, Pawlic M, Brzozowska I, Hahn EG (2000) Expression of cyclooxygenase (COX)-1 and COX-2 in adaptive cytoprotection induced by mild stress. J Physiol Pharmacol 94:83–91

    CAS  Google Scholar 

  15. Feng L, Sun W, Xia Y, Tang WW, Chanmugam P, Soyoola E, Wilson CB, Hwang D (1993) Cloning two isoforms of rat cyclooxygenase: Differential regulation of their expression. Arch Biochem Biophys 307:361–368

    Article  PubMed  CAS  Google Scholar 

  16. Kargman S, Charlesion S, Cartwright M, Frank J, Riendeaw D, Mancini J, Evans J, O’Neil G (1993) Characterization of prostaglandin G/H synthase 1 and 2 in rat, dog, monkey, and human gastrointestinal tracts. Gastroenterology 111:445–454

    Article  Google Scholar 

  17. Nobuhara Y, Ueki S, Takeuchi K (1985) Influence of prednisolone on gastric alkaline response in rat stomach; a possible explanation for steroid-induced gastric lesions. Dig Dis Sci 30:1166–1173

    Article  PubMed  CAS  Google Scholar 

  18. Tanaka A, Araki H, Hase S, Takeuchi K (2002) Roles of COX-1 and COX-2 inhibition in nonsteroidal antiinflammatory drug-induced gastric damage in rats: Relation to functional responses. Aliment Pharmacol Ther 16:90–101

    Article  PubMed  CAS  Google Scholar 

  19. Oyanagi Y (1984) Antiinflammatory effects of polyamines in serotonin and carragenan paw edemata: Possible mechanism to increase vascular permeability inhibitory protein level which is regulated by glucocorticoids and superoxide radicals. Agents Actions 14:228–237

    Article  Google Scholar 

  20. Nishino S, Arrigoni J, Shelton J, Kanbayashi T, Dement WC, Mignot E (1997) Effects of thyrotropin-releasing hormone and its analogs on daytime sleepiness and cataplexy in canine narcolepsy. J Neurosci 15:6401–6408

    Google Scholar 

  21. Futaki N, Takahashi S, Yokoyama M, Arai I, Higuchi S, Otomo S (1994) NS-398, a new antiinflammatory agent, selectively inhibits prostaglandin G/H synthase/cyclooxygenase (COX-2) activity in vitro. Prostaglandins 47:55–59

    Article  PubMed  CAS  Google Scholar 

  22. Tso JY, Sun XH, Kao TH, Reece KS, Wu R (1985) Isolation and characterization of rat and human glyceraldehyde-3-phosphate dehydrogenase cDNAs: Genomic complexity and molecular evolution of the gene. Nucleic Acids Res 13:2485–2502

    Article  PubMed  CAS  Google Scholar 

  23. Taché Y, Vale W, Brown M (1980) Thyrotropin–releasing hormone:CNS action to stimulate gastric acid secretion. Nature 287:149–151

    Article  PubMed  Google Scholar 

  24. Goto Y, Taché, Y (1985) Gastric erosions induced by intracisternal thyrotropin-releasing hormone in rats. Peptides 6:153–156

    Article  PubMed  CAS  Google Scholar 

  25. Taché Y, Yoneda M, Kato K, Kiraly A, Suto G, Kaneko H (1994) Intracisternal thyrotropin-releasing hormone-induced vagally mediated gastric protection against ethanol lesions: Central and peripheral mechanisms. J Gastroenterol Hepatol 9(Suppl 1):S29–S35

    PubMed  Google Scholar 

  26. Konturek PC, Brzozowski T, Ptak A, Kania J, Kwiecien S, Hahn EG, Konturek SJ (2002) Nitric oxide releasing aspirin protects the gastric mucosa against stress and promotes healing of stress-induced gastric mucosal damage: Role of heat shock protein 70. Digestion 66:160–172

    Article  PubMed  CAS  Google Scholar 

  27. Takeuchi K, Furukawa O, Tanaka H, Okabe S (1986) Determination of acid-neutralizing capacity in rat duodenum:Influences of 16,16-dimethyl prostaglandin E2 and nonsteroidal anti-inflammatory drugs. Dig Dis Sci 31:631–637

    Article  PubMed  CAS  Google Scholar 

  28. Horita A, Carino MA, Lai H (1986) Pharmacology of thyrotropin–releasing hormone (TRH). Annu Rev Pharmacol Toxicol 26:311–332

    Article  PubMed  CAS  Google Scholar 

  29. Takeuchi K, Nishiwaki H, Niida H, Okabe S (1990) Body temperature-dependent action of baclofen in the rat: Relation to acid secretion and ulcerogenecity. Dig Dis Sci 35:458–466

    Article  PubMed  CAS  Google Scholar 

  30. Kaneko H, Tache Y, Kusugami K (2002) Importance of medullary thyrotropin-releasing hormone in brain-gut circuits regulating gastric integrity: Preclinical studies. J Gastroenterol 37(Suppl 14):128–132

    PubMed  CAS  Google Scholar 

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Acknowledgments

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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  1. Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, 607-8414, Japan

    Akiko Tanaka, Ryo Hatazawa, Yuka Takahira, Nahoko Izumi, Ludmila Filaretova & Koji Takeuchi

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  1. Akiko Tanaka
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  2. Ryo Hatazawa
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  3. Yuka Takahira
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  4. Nahoko Izumi
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  5. Ludmila Filaretova
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  6. Koji Takeuchi
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Correspondence to Koji Takeuchi.

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Tanaka, A., Hatazawa, R., Takahira, Y. et al. Preconditioning Stress Prevents Cold Restraint Stress-Induced Gastric Lesions in Rats: Roles of COX-1, COX-2, and PLA2 . Dig Dis Sci 52, 478–487 (2007). https://doi.org/10.1007/s10620-006-9394-8

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  • DOI: https://doi.org/10.1007/s10620-006-9394-8

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