Ethanol stimulates pepsinogen release by opening a Ca2+ channel of guinea pig gastric chief cells.
To better understand the mechanism by which ethanol causes gastric mucosal injury, the effects of ethanol on isolated guinea pig gastric chief cells were investigated in vitro. Ethanol at 300-900 mmol/L dose-dependently stimulated an increase in pepsinogen release without affecting chief cells' viability. Ethanol stimulated an increase in initial Ca2+ influx rate and intracellular Ca2+ concentration at the same concentrations as it stimulated pepsinogen release, whereas it did not stimulate cyclic adenosine monophosphate accumulation. Pepsinogen release stimulated by 900 mmol/L ethanol was almost equal to that stimulated by 10(-8) mol/L COOH terminal octapeptide of cholecystokinin. Ethanol did not stimulate an increase in the accumulation of inositol trisphosphates and tetrakisphosphates in [3H]inositol-labeled chief cells, whereas cholecystokinin octapeptide caused a significant increase in inositol trisphosphates and tetrakisphosphates. Ethanol-stimulated pepsinogen release and increases in the initial Ca2+ influx rate and intracellular Ca2+ concentration were inhibited by 0.5 mmol/L La3+ or 1 mmol/L ethylene glycol tetraacetic acid but were not inhibited by nifedipine or verapamil. These results suggest that the effect of ethanol on pepsinogen release from the gastric chief cells may be due to its opening of a Ca2+ channel that is sensitive to La3+ and that the pepsinogen releasing action of ethanol may be one of factors for ethanol-induced gastric mucosal injury.
Konda
Y
Y
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Sakamoto
C
C
Nishisaki
H
H
Nakano
O
O
Matozaki
T
T
Nagao
M
M
Matsuda
K
K
Wada
K
K
Baba
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects*; D002478:Cells, Cultured; D000431:Ethanol / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006168:Guinea Pigs; D007295:Inositol Phosphates / Q000378:metabolism; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D010435:Pepsinogens / Q000378:metabolism*
D015220:Calcium Channels; D007295:Inositol Phosphates; D010435:Pepsinogens; D000431:Ethanol; D007811:Lanthanum; D002118:Calcium