AJP - Gastrointestinal and Liver Physiology, Vol 262, Issue 5 915-G920, Copyright © 1992 by American Physiological Society
Regulation of gastrin alpha-amidation in the developing rat stomach
L. R. Marino, B. H. Muglia and T. Yamada
Department of Pediatrics, University of Michigan Medical Center, Ann Arbor 48109.
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.
