Influence of chronic drug-induced achlorhydria by substituted benzimidazoles on the endocrine stomach in rats.

The release of gastric somatostatinlike immunoreactivity and gastrin was studied in rats with chronic achlorhydria induced by the substituted benzimidazole BY 308. In vitro, stimulation of gastrin release by acetylcholine was slightly enhanced after 1 day of treatment but no further effects were observed compared to placebo controls. Four weeks of treatment evoked marked gastrin hypersecretion, which was atropine-resistant. Stimulation of gastrin release was inversely correlated to enhancement of basal gastrin levels. Chronic achlorhydria distinctly reduced somatostatin responses to isoproterenol, whereas potent stimulation was observed in controls. Treatment with BY 308 for 1 wk was associated with fully developed gastrin hypersecretion but isoproterenol-stimulated somatostatin release was still unaffected. Hypergastrinemia accompanied by increased antral gastrin and reduced antral and fundic somatostatin concentrations was also found in vivo after 4 wk of treatment with BY 308. It is concluded that chronic achlorhydria not only enhances storage and secretion of gastrin but also diminishes the secretion and tissue stores of somatostatin; adaptive changes of the somatostatin cell occur, however, with a much longer delay.