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.