Stimulation of DNA synthesis by big and little gastrin (G-34 and G-17)

Fasted rats were injected six times over a 48-hr period with G-17 I, G-17 II, G-34 II in doses doubling from 3.38 nmoles per kg to 54 nmoles per kg. Twelve rats were studied at each dose. NaCl-injected animals were used as controls. The rats were killed and the in vitro incorporation of [3H]thymidine into DNA as well as the total DNA content of the mucosa of the duodenum and oxyntic gland area of the stomach were determined. All gastrins, as well as pentagastrin, stimulated DNA synthesis. Peak stimulation occurred at 13.5 nmoles per kg for G-17 I and G-17 II and at 6.75 nmoles per kg for G-34 II. Pentagastrin's peak trophic effect was produced by 325 nmoles per kg. In order to compare the efficacies of the various types of gastrins, 60 rats were divided into groups of 12. One group received saline and the other four groups received the maximally effective dose of one of the four types of gastrins. The responses to each of the gastrins were not significantly different, and DNA synthesis was doubled in each tissue. Total DNA content increased slightly, but significantly, in response to each gastrin. Several conclusions can be drawn from these data: (1) G-17 and G-34 possess trophic activity; (2) the efficacies of pentagastrin, G-17 I, G-17 II, and G-34 II for the stimulation of DNA synthesis are not significantly different; (3) sulfation of G-17 has no significant effect on its trophic activity; (4) based on the effects of exogenous molar doses and their respective half-lives, both G-17 and G-34 would be expected to contribute to the trophic effect of endogenous gastrin; and (5) G-17 and G-34 are at least as effective in stimulating DNA synthesis as they are in stimulating gastric acid secretion.