Effect of pirenzepine on gastric endocrine cell kinetics during lansoprazole administration

Abstract

We studied the effect of pirenzepine on gastric secretion kinetics in rats in a hypochlorhydric state induced by lansoprazole, a proton pump inhibitor. Pirenzepine was administered intramuscularly at a dosage of 20 mg/kg twice daily; and lansorprazole, subcutaneously at 50 mg/kg once daily, both every day for 4 weeks. After the 4-week treatment, serum gastrin and plasma somatostatin levels were determined by radioimmunoassay. In addition, gastrin cells, somatostatin cells, and enterochromaffin-like cells were immunostained and counted. Serum gastrin levels were elevated, and gastrin and enterochromaffin-like cell numbers increased in the group on lansoprazole alone, compared with these values in the control group (which received distilled water). In the group on the lansoprazole and pirenzepine combination, serum gastrin levels decreased, and gastrin and enterochromaffin-like cell numbers were significantly decreased, compared with the respective variables in the group on lansoprazole alone, while the number of somatostatin cells increased in the group on the combination. Plasma somatostatin levels did not vary significantly in any group. It was thus demonstrated that pirenzepine corrects the abnormal gastric secretion kinetics resulting from treatment with lansoprazole alone, such as hypergastrinemia and gastrin and enterochromaffin-like cell hyperplasia.

Pathological effects of drugs on the gastrointestinal tract: a review

“…This enlargement is due to parietal cell hypertrophy and is accompanied by hyperplasia. These changes are thought to be due to PPIinduced hypergastrinemia, and studies have shown that the antrum can show increased numbers of gastrin-secreting G cells [15,16]. On a practical level, hypertrophy and hyperplasia are noted by the presence of parietal cell extension up to the level of the foveolar neck region, as well as enlarged, crowded parietal cells with luminal bulging within deeper glands (parietal cell protrusions), and are highly suggestive of PPI use (Fig.…”

Mechanism of gastric mucosal proliferation induced by gastrin

“… 14 In animal experiments, hypergastrinaemia, even if induced by exogenous administration of gastrin or caused by proton pump inhibitor‐induced inhibition of gastric acid secretion, had a potent selective trophic effect on gastric ECL cells. 15–17 These clinical and experimental data suggest that gastrin directly stimulates only the proliferation of ECL cells in the gastric mucosa.…”

Does pirenzepine suppress the undesirable effects of a proton pump inhibitor on enterochromaffin-like cells?

“…The finding of Tari et al 9 suggests that somatostatin, which is secreted by fundic D cells, may be involved in the mechanism by which pirenzepine inhibits the omeprazole-induced histamine secretion and synthesis in ECL cells. Omura et al 11 have shown that pirenzepine suppresses the increase in the number of ECL cells induced by lansoprazole in the rat. Pirenzepine may suppress not only histamine secretion and synthesis but may also inhibit the proliferation of ECL that is induced by a proton pump inhibitor.…”