Effects of long-term omeprazole treatment on adult rat gastric mucosa--enhancement of the epithelial cell proliferation and suppression of its differentiation.
Effects of long-term omeprazole treatment on the process of epithelial cell proliferation and differentiation in the adult rat gastric mucosa were investigated. Animals were treated with omeprazole (25 mg/kg body weight/day) for 28 days to induce anacidity in the stomach. The treatment induced a marked decrease in the number of chief cells in the gastric mucosa and at the same time an increase in that of immature pepsinogen-producing cells expressing class III mucin. This was accompanied by a decrease to 60% and 10% of the control values in the mucosal levels of pepsinogen and its mRNA, respectively. Moreover, the expression of cathepsin E in surface mucous cells was reduced. Cell proliferation studies revealed that the rate of bromodeoxyuridine-labeled cells was increased by omeprazole. The above-described changes were reversed by cessation of the treatment and they were not caused by the omeprazole-treatment at a dose which does not induce anacidity in the stomach. These results suggest that long-term omeprazole treatment reversibly increases the epithelial cell proliferation and suppresses its differentiation in the adult rate gastric mucosa probably by altering the acidic environment specific for the stomach.
Kakei
N
N
First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Ichinose
M
M
Tatematsu
M
M
Shimizu
M
M
Oka
M
M
Yahagi
N
N
Matsushima
M
M
Kurokawa
K
K
Yonezawa
S
S
Furihata
C
C
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D020059:Cathepsin E; D002403:Cathepsins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D005755:Gastrins / Q000097:blood; D015870:Gene Expression / Q000187:drug effects; D007700:Kinetics; D008297:Male; D009077:Mucins / Q000096:biosynthesis; D009853:Omeprazole / Q000494:pharmacology*; D010435:Pepsinogens / Q000096:biosynthesis / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000897:Anti-Ulcer Agents; D005755:Gastrins; D009077:Mucins; D010435:Pepsinogens; D012333:RNA, Messenger; D002403:Cathepsins; D020059:Cathepsin E; D009853:Omeprazole