Attenuation of trophic response to gastrin after inhibition of ornithine decarboxylase
- 1 July 1985
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Gastrointestinal and Liver Physiology
- Vol. 249 (1), G16-G20
- https://doi.org/10.1152/ajpgi.1985.249.1.g16
Abstract
The mechanism by which the hormone gastrin induces growth of the gastrointestinal mucosa is unknown. Many hormones are inducers of ornithine decarboxylase (ODC), the rate-limiting enzyme in the synthesis of the polyamines putrescine, spermidine, and spermine. Although the exact biochemical function of the polyamines is not completely understood, they appear to be required for normal cell growth and differentiation. Rats were maintained on a liquid diet for 5 days and treated with difluoromethylornithine (DFMO, 200 mg/kg ip, 3 times/day), a selective, irreversible inhibitor of ODC, for 5 days. Half of these animals also received pentagastrin (250 mg/kg ip) during the final 3 days of the treatment schedule. DFMO alone had no effect on body weight or mucosal growth. Pentagastrin increased total RNA, DNA, and protein in the oxyntic gland and duodenal and colonic mucosa. Concurrent treatment with DFMO completely inhibited the trophic response to pentagastrin in the oxyntic gland area of the stomach and the duodenal mucosa. In contrast, DFMO was without effect on response of the colonic mucosa to pentagastrin. Pentagastrin treatment did not induce the mucosal ODC activity of the oxyntic gland area of the stomach, the duodenum, the ileum, or the proximal colon of either animals fasted for 48 h or animals maintained on a liquid diet. ODC activity was measured at 4, 8, 12, and 24 h after administration of hormone. These results suggest that, in at least the proximal bowel, the stimulation by gastrin of nucleic acid and protein synthesis requires intact polyamine synthesis but that gastrin itself does not induce ODC.This publication has 8 references indexed in Scilit:
- Polyamines in the response to intestinal obstructionAmerican Journal of Physiology-Gastrointestinal and Liver Physiology, 1984
- Measurement of the number of ornithine decarboxylase molecules in rat and mouse tissues under various physiological conditions by binding of radiolabelled α-difluoromethylornithineBiochemical Journal, 1982
- Stimulation of rat oxyntic gland mucosal growth by epidermal growth factorAmerican Journal of Physiology-Gastrointestinal and Liver Physiology, 1980
- Mucosal gastrin receptor. I. Assay standardization and fulfillment of receptor criteria.American Journal of Physiology-Endocrinology and Metabolism, 1979
- Effect of α-difluoromethylornithine, an enzyme-activated irreversible inhibitor of ornithine decarboxylase, on polyamine levels in rat tissuesLife Sciences, 1979
- Epidermal Growth Factor Stimulates Ornithine Decarboxylase Activity in the Digestive Tract of MouseExperimental Biology and Medicine, 1978
- Ornithine decarboxylase in rat small intestine: stimulation with food or insulinAmerican Journal of Physiology-Legacy Content, 1976
- Stimulation of DNA Synthesis by Big and Little Gastrin (G-34 and G-17)Gastroenterology, 1976