Regulation of gastrin alpha-amidation in the developing rat stomach.

Because the gastrin molecule must be alpha-amidated to have maximum biological activity, rat pups from 1 to 6 wk of age were treated with dexamethasone (2 mg.kg-1.day-1) for 3 or 7 days, diethyldithiocarbamate (DDC; 400 mg.kg-1.day-1 x 3 days), dexamethasone and DDC, pentagastrin (750 micrograms.kg-1.day-1), or bombesin (40 micrograms.kg-1.day-1) for 3 days to determine the effects of these agents on alpha-amidation and gastrin and glycine extended gastrin (G-Gly) concentration in the stomach. Three day treatment with dexamethasone increased gastrin concentration by increasing amidation in pups before 5 wk of age and thereafter by enhancing preprogastrin synthesis or processing. Seven day dexamethasone treatment had no substantial effect on amidation. DDC universally inhibited amidation and affected a sustained increase in gastrin plus G-Gly concentration after the third week of life. Dexamethasone did not reverse the effects of DDC. Pentagastrin increased amidation in 1-, 3-, and 6-wk old rat pups but had no consistent effect on peptide concentration. Bombesin increased the sum of gastrin and G-Gly concentration in all but 1- and 5-wk old pups but had variable effects on alpha-amidation. We conclude that alterations in gastrin alpha-amidation have age-specific effects on tissue gastrin and G-Gly concentration and speculate that changes in tissue gastrin and G-Gly stores available for release might ultimately affect parietal cell and G-cell function during development.

H(+)-K(+)-ATPase and carbonic anhydrase II gene expression in the developing rat fundus.

H(+)-K(+)-ATPase and carbonic anhydrase II (CA II) are two enzymes that are involved in the production and secretion of the hydrogen ion by the gastric parietal cell and maintenance of intracellular pH therein. The present studies were undertaken to examine whether H(+)-K(+)-ATPase and CA II expression change in the rat fundus in association with the development of acid secretory capacity. Changes in enzyme mRNA content in the gastric fundus of developing rat pups 1-6 wk of age were evaluated using dot blots and ribonuclease protection assays. In additional studies the localization of H(+)-K(+)-ATPase and carbonic anhydrase II mRNA was examined by in situ hybridization in Formalin-fixed gastric tissues from rats 1, 3, 6, and 8 wk of age. We observed that H(+)-K(+)-ATPase mRNA content increased with age in the developing rat fundus while CA II mRNA exhibited a reciprocal decrease. These changes in enzyme mRNA were accompanied by concomitant changes in the regional distribution of the cells expressing the genes for the two enzymes. Although the changes in H(+)-K(+)-ATPase mRNA paralleled the development of acid secretory capacity, CA II mRNA levels might be regulated by the requirement for maintenance of intracellular pH during periods of cellular proliferation and by exposure of the gastric surface epithelium to the highly acidic luminal environment of the stomach.