Effect of rabeprazole on histamine synthesis in enterochromaffin-like cells of mast cell-deficient (Ws/Ws) rats.
The effect of rabeprazole, the latest proton pump inhibitor, on the serum gastrin concentration, histidine decarboxylase activity and histamine content of the oxyntic mucosa in Wistar rats, mast cell-deficient (Ws/Ws) rats, and their normal type, +/+, rats was investigated. In Wistar rats, 2 weeks of treatment with rabeprazole (30 mg/kg/day, s.c.) induced a 1.8-fold increase in serum gastrin concentration and a 3.9-fold increase in histidine decarboxylase activity of the oxyntic mucosa over the control levels, whereas neither 2- nor 4-week treatment affected the histamine content of the oxyntic mucosa. In Ws/Ws and +/+ rats, the serum gastrin concentration, histidine decarboxylase activity and even histamine content of the oxyntic mucosa were increased significantly as compared with control levels after the 4-week treatment with rabeprazole. Immunohistochemistry using a histamine antibody confirmed the increase in the histamine content of the oxyntic mucosa after the 4-week treatment with rabeprazole. The finding that there were no differences in serum gastrin concentration and histidine decarboxylase activity between Ws/Ws and +/+ rats, both with and without the 4-week treatment, indicates that mast cells do not respond to endogenous hypergastrinemia elicited by acid-inhibitory treatment. Moreover, the present study clarified for the first time that enterochromaffin-like (ECL) cells in Ws/Ws rats synthesize and store histamine in response to gastrin.
Nakamura
S
S
Third Department of Internal Medicine, Ehime University, School of Medicine, Shigenobu-cho, Onsen-gun, Ehime, Japan.
Watanabe
H
H
Yokota
T
T
Matsui
H
H
Onji
M
M
Maeyama
K
K
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D002455:Cell Division; D004759:Enterochromaffin Cells / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism*; D005755:Gastrins / Q000097:blood / Q000502:physiology; D006632:Histamine / Q000032:analysis / Q000096:biosynthesis*; D006640:Histidine Decarboxylase / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D009853:Omeprazole / Q000031:analogs & derivatives; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D051381:Rats; D017208:Rats, Wistar
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D005755:Gastrins; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D006632:Histamine; D006640:Histidine Decarboxylase; D009853:Omeprazole