Vioxx Research Today is a free monthly online journal that collates and summarizes the latest research about Vioxx, including details on osteoarthritis, side-effects, trials, stroke, heart attack. | ||||||||
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Cyclooxygenase 1 is required for pH control at the mouse gastric surface.Baumgartner HK, Starodub OT, Joehl JS, Tackett L, Montrose MH University of Cincinnati, Department of Molecular and Cellular Physiology, 231 Albert Sabin Way, Cincinnati, OH 45267, USA. BACKGROUND: Endogenous cyclooxygenase (COX) activity is required to maintain a relatively alkaline surface pH at the gastric luminal surface. AIMS: The purpose of this study was to determine which COX isoform, COX-1 or COX-2, is responsible for regulating the protective surface pH gradient and to test if COX inhibitors also had non-COX mediated effects in vivo. METHODS: Immunofluorescence and western blot analysis showed constitutive expression of both COX isoforms in the normal mouse stomach. We used in vivo confocal microscopy to measure pH near the mucosal surface of anaesthetised COX-1 (-/-), COX-2 (-/-), or wild-type mice of the same genetic background. RESULTS: When the gastric mucosal surface was exposed and superfused (0.2 ml/min) with a weakly buffered saline solution (pH 3) containing the pH indicator Cl-NERF, the pH directly at the gastric surface and thickness of the pH gradient were similar in wild-type and COX-2 (-/-) mice, but COX-1 (-/-) mice had a significantly thinner pH gradient. Addition of indomethacin had minimal effects on the residual surface pH gradient in COX-1 (-/-) mice, suggesting no role for COX-2 in surface pH regulation. Whole stomach perfusion studies demonstrated diminished net alkali secretion in COX-1 (-/-) mice, and application of SC-560 or rofecoxib to wild-type mice and mutant mice confirmed that only COX-1 inhibition reduced alkali secretion. CONCLUSION: COX-1 is the dominant isoform regulating the normal thickness of the protective surface pH gradient in mouse stomach. Published 15 November 2004 in Gut, 53(12): 1751-7.
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