Lansoprazole and Omeprazole Have Similar Effects on Plasma Gastrin Levels, Enterochromaffin-Like Cells, Gastrin Cells and Somatostatin Cells in the Rat Stomach

Abstract

This study compares the effects of lansoprazole and omeprazole on the activation and proliferation of enterochromaffin-like (ECL) cells in the rat stomach. Lansoprazole was given orally once daily for 10 weeks in two doses, 135 and 200 μmol/kg. Omeprazole was given by the same regimen in a dose of 400 μmol/kg, which is equipotent in terms of acid inhibition to the higher lansoprazole dose. Lansoprazole (both doses) as well as omeprazole raised the plasma gastrin levels about 11 -fold 2 h after dosing and 8- to 10-fold 24 h after dosing, reflecting complete (2 h) and 70-80% (24 h) reductions of gastric acid secretion. Administration of either drug for 10 weeks increased the weight of the stomach and the oxyntic mucosa. The oxyntic mucosal histidine decarboxylase activity, histamine concentration and ECL cell density were increased to the same extent in the rats given either of the two lansoprazole doses or omeprazole. The numbers of antral gastrin cells were doubled and the numbers of antral somatostatin cells half that in the controls. These results show that long-standing lansoprazole-evoked hypergastrinemia affects the ECL cell similarly to omeprazole, ranitidine and other acid secretion inhibitors.

Chronic Gastritis

“…It can be assumed that the increasing number of CgA cells in the prepyloric mucosa means simultaneous increase of G cell count. Therefore, the results obtained in own studies may be regarded as a confirmation of the fact already known from papers by other authors (Chamouard et al, 1997;Graham et al, 1993;Kozlowski et al, 1993Kozlowski et al, , 1995Tzaneva & Julianov, 1999) and also obtained empirically (Lee et al, 1992) which point to participation of disturbances of interrelations between D and G cells in the pathomechanism of hypergastrinaemia that accompanies Helicobacter pylori colonization of gastric mucosa. It should be stressed that due to other causes, e.g.…”

Abnormal functional and morphological regulation of the gastric mucosa in histamine H2 receptor–deficient mice

“…It has been observed that treatment with antiulcer agents such as H2R antagonists and PPIs induced hypergastrinemia and hypertrophy of the gastric mucosa in rodents (14,16). In the present study, serum gastrin levels, wet weights, and DNA contents of the stomach were assessed in H2R -/-mice.…”

“…Chronic application of acidinhibitory drugs elevates serum gastrin levels (14,16,30), and it has been suggested that the gastric pH influences the population of endocrine cells such as gastrinproducing G cells (30)(31)(32). The long-term elevation of gastric pH may increase G-cell density and then elevate serum gastrin levels.…”

“…Because gastrin has a powerful trophic effect on oxyntic mucosal cells in vivo (15)(16)(17)(18)(19)(20)23) as well as in vitro (33,34), it is probable that the elevated levels of serum gastrin contribute to the hypertrophy in H2R-deficient mice. However, the study using a gastric adenocarcinoma cell line has revealed that H2R antagonists, roxatidine and ranitidine, enhanced parietal cell proliferation without any increase in the amount of mRNA expression of either TGF-α or EGFR, indicating that the H2R-mediated signal may be involved in the gastric cell proliferation (21).…”

“…The trophic effect of gastrin for oxyntic mucosa has also been studied. Longterm administration of gastrin, histamine H2R antagonist, or proton pump inhibitor (PPI) increased plasma gastrin concentration and lead to hypertrophy of oxyntic mucosa, caused by increased numbers of mucosal cells (14)(15)(16). In addition, recent studies using genetically engineered mice deficient in gastrin or CCK-BR have demonstrated the importance of gastrin signal(s) as a trophic effect on oxyntic mucosa (17)(18)(19)(20).…”