The effects of prolonged administration of cimetidine or pirenzepine on gastric mucosal cell kinetics, serum gastrin levels and acid secretory responses in rats.

60 days' treatment of rats with cimetidine 160 mg/kg/die per os produced a significant increase in total gastrin cell number, gastrin cell density of antral mucosa as well as parietal cell density of fundic mucosa as compared with controls. By contrast, the same parameters significantly decreased in rats treated for 60 days with pirenzepine 16 mg/kg/die per os. Under the same conditions, immunoreactive serum gastrin levels were found to be significantly enhanced in cimetidine-treated rats, but not significantly changed in rats treated with pirenzepine. 48 hours after drug withdrawal, gastric secretory responses to pentagastrin were found to be significantly increased in cimetidine-treated rats and decreased in pirenzepine-treated rats. These results suggest that a feed-back reaction to cimetidine-induced prolonged hypochlorhydria mediates hyperactivity of the gastrin cell system which, in turn, induces parietal-cell hyperplasia. The hyperplasia accounts for hypersecretive responses in cimetidine-treated rats. The inhibitory activity displayed by pirenzepine on the same parameters may be due to the blockade of vagal trophic influences on gastric mucosal cells and/or to the release of inhibitory factors such as somatostatin.