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 g astrin concentration, histidine decarboxylase activity and histamine conten t of the oxyntic mucosa in Wistar rats, mast cell-deficient (Ws/Ws) rats. a nd their normal type, +/+, rats was investigated. In Wistar rats, 2 weeks o f treatment with rabeprazole (30 mg/kg/day, s.c.) induced a 1.8-fold increa se in serum gastrin concentration and a 3.9-fold increase in histidine deca rboxylase activity of the oxyntic mucosa over the control levels, whereas n either 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 wer e 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 afte r the 4-week treatment with rabeprazole. The finding that there were no dif ferences in serum gastrin concentration and histidine decarboxylase activit y between Ws/Ws and +/+ rats, both with and without the 4-week treatment, i ndicates that mast cells do not respond to endogenous hypergastrinemia elic ited by acid-inhibitory treatment. Moreover, the present study clarified fo r the first time that enterochromaffin-like (ECL) cells in Ws/Ws rats synth esize and store histamine in response to gastrin. (C) 2000 Elsevier Science B.V. All rights reserved.