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Haber PS, Gentry RT, Mak KM, Mirmiran-Yazdy SA, Greenstein RJ, Lieber CS: Metabolism of alcohol by human gastric cells: relation to first-pass metabolism. Gastroenterology. 1996 Oct;111(4):863-70.
BACKGROUND & AIMS: The bioavailability of orally administered alcohol is incomplete, indicating first-pass metabolism. There is debate regarding the site of first-pass metabolism and specifically whether the stomach has the metabolic capacity to account for first-pass metabolism. The aim of this study was to assess ethanol metabolism by human gastric mucosa cells in primary culture. METHODS: Cells were incubated with [1-14C] ethanol, and the quantity of ethanol oxidized was measured by the production of [1-14C] acetate. RESULTS: Gastric cells cultured from men produced 7.3 +/- 3.5 mumol acetate.10 (6) cells-1.h-1, which was more than that generated in cells from women (3.2 +/- 0.6; P < 0.05). Acetate production was inhibited by 4-methylpyrazole (a class I alcohol dehydrogenase [ADH] inhibitor) and by m-nitrobenzaldehyde (a selective substrate for class IV ADH isoenzyme) but not by sodium azide (a catalase inhibitor). Cimetidine (a gastric ADH inhibitor) reduced acetate production by as much as 59%, whereas ranitidine had no significant effect. CONCLUSIONS: Human gastric cells metabolize sufficient alcohol to account for the bulk of first-pass metabolism. At least two isozymes of gastric ADH contribute to this metabolism. Cimetidine, but not ranitidine, inhibits gastric alcohol metabolism in keeping with its inhibition of in vivo first-pass metabolism. |
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