Metabolism of alcohol by human gastric cells: relation to first-pass metabolism.
OBJECTIVE
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.
Haber
P S
PS
Alcohol Research and Treatment Center, Bronx Veterans Affairs Medical Center, New York, USA.
Gentry
R T
RT
Mak
K M
KM
Mirmiran-Yazdy
S A
SA
Greenstein
R J
RJ
Lieber
C S
CS
D019342:Acetic Acid / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000426:Alcohol Dehydrogenase / Q000502:physiology; D002478:Cells, Cultured; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D008297:Male; D008875:Middle Aged
D007527:Isoenzymes; D000431:Ethanol; D000426:Alcohol Dehydrogenase; D019342:Acetic Acid