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.
Marino
L R
LR
Department of Pediatrics, University of Michigan Medical Center, Ann Arbor 48109.
Muglia
B H
BH
Yamada
T
T
D000375:Aging / Q000378:metabolism*; D000577:Amides / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development* / Q000378:metabolism; D001839:Bombesin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004050:Ditiocarb / Q000494:pharmacology; D005753:Gastric Mucosa / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism*; D010418:Pentagastrin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000254:growth & development
D000577:Amides; D005755:Gastrins; D003907:Dexamethasone; D004050:Ditiocarb; D010418:Pentagastrin; D001839:Bombesin