GASTRIN CELL RESPONSES TO ACIDIFICATION OF THE ACHLORHYDRIC RAT STOMACH

In the rat, gastrin cells are normally exposed to the stimulatory effe cts of food and the inhibitory influences of acid in the gastric lumen . We have studied the effects of intragastric acid on gastrin cell fun ction in animals in which the tonic inhibitory action of acid was remo ved by prior treatment with the proton pump blocker omeprazole. In fas ted rats with gastric fistula treated with omeprazole, instillation of acid into the stomach produced a prompt decrease in plasma gastrin, b ut gastrin mRNA abundance showed a modest transient increase over a pe riod of 2 h and thereafter no change; there was also a transient incre ase in tissue concentrations of the gastrin precursor progastrin that was compatible with increased gastrin synthesis. Concentrations of tis sue gastrins, in general, increased after acid instillation, which can be attributed to continued synthesis in the presence of suppressed ga strin release. In rats fed ad libitum, a single dose of omeprazole (wh ich produces achlorhydria for 24-30 h) produced an increase in plasma gastrin that peaked after 24 h and declined to control levels over the following 48 h; in contrast, gastrin mRNA abundance peaked 48 h after omeprazole before declining to control levels. The results indicate t hat whereas gastrin release might be promptly inhibited by intragastri c acid, the changes in gastrin mRNA abundance are much slower: achlorh ydria increases gastrin mRNA within 24 h, but acid takes longer to dep ress gastrin mRNA abundance. Over periods of a few hours, gastrin rele ase and synthesis need not, therefore, change in parallel.