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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

Cyclooxygenase (COX)-1 and COX-2 Both Play an Important Role in the Protection of the Duodenal Mucosa in Cats

Hiroshi Satoh, Kikuko Amagase, Satomi Ebara, Yasutada Akiba and Koji Takeuchi
Journal of Pharmacology and Experimental Therapeutics January 2013, 344 (1) 189-195; DOI: https://doi.org/10.1124/jpet.112.199182
Hiroshi Satoh
Department of Pharmacology and Experimental Therapeutics, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan (H.S., K.A., K.T.); Department of Anatomy, Medical Education and Research Center, Meiji University of Integrative Medicine, Kyoto, Japan (S.E.); and Greater Los Angeles Veterans Affair Healthcare System, Center for Ulcer Research and Education/University of California, Los Angeles Medical School, Brentwood Biomedical Research Institute, Los Angeles, California (Y.A.)
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Kikuko Amagase
Department of Pharmacology and Experimental Therapeutics, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan (H.S., K.A., K.T.); Department of Anatomy, Medical Education and Research Center, Meiji University of Integrative Medicine, Kyoto, Japan (S.E.); and Greater Los Angeles Veterans Affair Healthcare System, Center for Ulcer Research and Education/University of California, Los Angeles Medical School, Brentwood Biomedical Research Institute, Los Angeles, California (Y.A.)
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Satomi Ebara
Department of Pharmacology and Experimental Therapeutics, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan (H.S., K.A., K.T.); Department of Anatomy, Medical Education and Research Center, Meiji University of Integrative Medicine, Kyoto, Japan (S.E.); and Greater Los Angeles Veterans Affair Healthcare System, Center for Ulcer Research and Education/University of California, Los Angeles Medical School, Brentwood Biomedical Research Institute, Los Angeles, California (Y.A.)
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Yasutada Akiba
Department of Pharmacology and Experimental Therapeutics, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan (H.S., K.A., K.T.); Department of Anatomy, Medical Education and Research Center, Meiji University of Integrative Medicine, Kyoto, Japan (S.E.); and Greater Los Angeles Veterans Affair Healthcare System, Center for Ulcer Research and Education/University of California, Los Angeles Medical School, Brentwood Biomedical Research Institute, Los Angeles, California (Y.A.)
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Koji Takeuchi
Department of Pharmacology and Experimental Therapeutics, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan (H.S., K.A., K.T.); Department of Anatomy, Medical Education and Research Center, Meiji University of Integrative Medicine, Kyoto, Japan (S.E.); and Greater Los Angeles Veterans Affair Healthcare System, Center for Ulcer Research and Education/University of California, Los Angeles Medical School, Brentwood Biomedical Research Institute, Los Angeles, California (Y.A.)
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Abstract

Although nonsteroidal anti-inflammatory drugs often cause ulcers in the duodenum in humans, the role of cyclooxygenase (COX) isoforms in the pathogenesis of duodenal ulcers has not been fully elucidated. We examined in cats the 1) ulcerogenic effects of selective COX-1 (SC-560, ketorolac) and COX-2 (celecoxib, meloxicam) inhibitors on the gastrointestinal mucosa, 2) effect of feeding and cimetidine on the expression of COX isoforms and prostaglandin E2 (PGE2) level in the duodenum, and 3) localization of COX isoforms in the duodenum. COX inhibitors were administered after the morning meal in cats once daily for 3 days. Gastrointestinal lesions were examined on day 4. Localization and expression of COX isoforms (by immunohistochemistry, Western blot) and PGE2 level (by enzyme immunoassay) were examined. Results were as follows. First, selective COX-1 or COX-2 inhibitors alone produced marked ulcers in the duodenum but did not cause obvious lesions in the small intestine. Coadministration of SC-560 and celecoxib produced marked lesions in the small intestine. Second, feeding increased both the expression of COX isoforms and PGE2 level in the duodenum, and the effects were markedly inhibited by pretreatment with cimetidine. Third, COX-1 was localized in goblet and Brunner’s gland cells, Meissner’s and Auerbach’s plexus, smooth muscle cells, and arterioles; and COX-2 was observed in capillaries, venules, and basal granulated cells. The expression of COX isoforms in the duodenum is up-regulated by feeding, and inhibition of either COX-1 or COX-2 causes ulcers in the duodenum, suggesting that both isoforms play an important role in the protection of the duodenal mucosa.

Footnotes

  • dx.doi.org/10.1124/jpet.112.199182.

  • Received August 8, 2012.
  • Accepted September 21, 2012.
  • U.S. government work not protected by U.S. copyright.
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Journal of Pharmacology and Experimental Therapeutics: 344 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 344, Issue 1
1 Jan 2013
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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

Role of COX in the Protection of Duodenal Mucosa

Hiroshi Satoh, Kikuko Amagase, Satomi Ebara, Yasutada Akiba and Koji Takeuchi
Journal of Pharmacology and Experimental Therapeutics January 1, 2013, 344 (1) 189-195; DOI: https://doi.org/10.1124/jpet.112.199182

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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

Role of COX in the Protection of Duodenal Mucosa

Hiroshi Satoh, Kikuko Amagase, Satomi Ebara, Yasutada Akiba and Koji Takeuchi
Journal of Pharmacology and Experimental Therapeutics January 1, 2013, 344 (1) 189-195; DOI: https://doi.org/10.1124/jpet.112.199182
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