Abstract
While the proliferative effects of gastrin in the gastric fundus are well established, there is a considerable degree of confusion regarding the role of gastrin on the growth of the small intestine and colon. The hypothesis that gastrin is trophic throughout the gut was tested by giving three doses of pentagastrin and one of gastrin 17 to rats maintained by total parenteral nutrition (TPN). The rats were fed intravenously for one week, with the various peptides added to the TPN diet. The number of vincristine arrested metaphases per gland or crypt was then scored to determine the proliferative state. Both gastrin 17 and pentagastrin were found to be trophic in the gastric fundus, but not to the gastric antrum. A proliferative response was also seen in the duodenum, but with little evidence of a dose response element. No effect on small bowel weight was seen, and no proliferative effect was noted in the mid small bowel, thus the duodenal effect could be attributed to a local action of increased acid output on the duodenum, not a general role throughout the small intestine. No proliferative effects of pentagastrin or gastrin were seen in the colon. It is therefore concluded that the trophic role of gastrin is restricted to the gastric fundus and the proximal duodenum.
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Selected References
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- Carlsson E., Havu N., Mattsson H., Ekman L. Gastrin and gastric enterochromaffin-like cell carcinoids in the rat. Digestion. 1990;47 (Suppl 1):17–52. doi: 10.1159/000200510. [DOI] [PubMed] [Google Scholar]
- Casteleyn P. P., Dubrasquet M., Willems G. Opposite effects of gastrin on cell proliferation in the antrum and other parts of the upper-gastrointestinal tract in the rat. Am J Dig Dis. 1977 Sep;22(9):798–804. doi: 10.1007/BF01694510. [DOI] [PubMed] [Google Scholar]
- Chu M., Rehfeld J. F., Borch K. Effects of gastric fundectomy and antrectomy on the colonic mucosa in the hamster. Digestion. 1992;53(1-2):28–34. doi: 10.1159/000200968. [DOI] [PubMed] [Google Scholar]
- Eggstein S., Imdahl A., Kohler M., Waibel M., Farthmann E. H. Influence of gastrin, gastrin receptor blockers, epidermal growth factor, and difluoromethylornithine on the growth and the activity of ornithine decarboxylase of colonic carcinoma cells. J Cancer Res Clin Oncol. 1991;117(1):37–42. doi: 10.1007/BF01613194. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fatemi S. H., Cullan G. E., Sharp J. G. Evaluation of the effects of pentagastrin, gastrin and pancreatic glucagon on cell proliferation in the rat gastrointestinal tract. Cell Tissue Kinet. 1984 Mar;17(2):119–133. doi: 10.1111/j.1365-2184.1984.tb00574.x. [DOI] [PubMed] [Google Scholar]
- Finney K. J., Appleton D. R., Ince P., Moorghen M., Elliott K., Watson A. J. Effects of gastrointestinal peptides on azoxymethane-treated colonic mucosa in vitro. Carcinogenesis. 1991 Nov;12(11):2017–2022. doi: 10.1093/carcin/12.11.2017. [DOI] [PubMed] [Google Scholar]
- Goodlad R. A., Al-Mukhtar M. Y., Ghatei M. A., Bloom S. R., Wright N. A. Cell proliferation, plasma enteroglucagon and plasma gastrin levels in starved and refed rats. Virchows Arch B Cell Pathol Incl Mol Pathol. 1983;43(1):55–62. doi: 10.1007/BF02932943. [DOI] [PubMed] [Google Scholar]
- Goodlad R. A., Ghatei M. A., Domin J., Bloom S. R., Gregory H., Wright N. A. Plasma enteroglucagon, peptide YY and gastrin in rats deprived of luminal nutrition, and after urogastrone-EGF administration. A proliferative role for PYY in the intestinal epithelium? Experientia. 1989 Feb 15;45(2):168–169. doi: 10.1007/BF01954862. [DOI] [PubMed] [Google Scholar]
- Goodlad R. A., Wilson T. J., Lenton W., Gregory H., McCullagh K. G., Wright N. A. Intravenous but not intragastric urogastrone-EGF is trophic to the intestine of parenterally fed rats. Gut. 1987 May;28(5):573–582. doi: 10.1136/gut.28.5.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goodlad R. A., Wilson T. J., Lenton W., Gregory H., McCullough K. G., Wright N. A. Urogastrone-epidermal growth factor is trophic to the intestinal epithelium of parenterally fed rats. Experientia. 1985 Sep 15;41(9):1161–1163. doi: 10.1007/BF01951708. [DOI] [PubMed] [Google Scholar]
- Goodlad R. A., Wright N. A. Growth control factors in the gastrointestinal tract. Baillieres Clin Gastroenterol. 1990 Mar;4(1):97–118. doi: 10.1016/0950-3528(90)90041-e. [DOI] [PubMed] [Google Scholar]
- Hanson W. R. Proliferative and morphological adaptation of the intestine to experimental resection. Scand J Gastroenterol Suppl. 1982;74:11–20. [PubMed] [Google Scholar]
- Håkanson R., Blom H., Carlsson E., Larsson H., Ryberg B., Sundler F. Hypergastrinaemia produces trophic effects in stomach but not in pancreas and intestines. Regul Pept. 1986 Feb;13(3-4):225–233. doi: 10.1016/0167-0115(86)90041-8. [DOI] [PubMed] [Google Scholar]
- Johnson L. R. New aspects of the trophic action of gastrointestinal hormones. Gastroenterology. 1977 Apr;72(4 PT2):788–792. [PubMed] [Google Scholar]
- Johnson L. R. The trophic action of gastrointestinal hormones. Gastroenterology. 1976 Feb;70(2):278–288. [PubMed] [Google Scholar]
- Lamote J., Willems G. Stimulating effect of pentagastrin on cancer cell proliferation kinetics in chemically induced colon cancer in rats. Regul Pept. 1988 Jan;20(1):1–9. doi: 10.1016/0167-0115(88)90052-3. [DOI] [PubMed] [Google Scholar]
- Levi S., Goodlad R. A., Lee C. Y., Stamp G., Walport M. J., Wright N. A., Hodgson H. J. Inhibitory effect of non-steroidal anti-inflammatory drugs on mucosal cell proliferation associated with gastric ulcer healing. Lancet. 1990 Oct 6;336(8719):840–843. doi: 10.1016/0140-6736(90)92341-e. [DOI] [PubMed] [Google Scholar]
- Majumdar A. P. Effects of fasting and refeeding on antral, duodenal, and serum gastrin levels and on colonic thymidine kinase activity in rats. Horm Res. 1984;19(2):127–134. doi: 10.1159/000179877. [DOI] [PubMed] [Google Scholar]
- Mak K. M., Chang W. W. Pentagastrin stimulates epithelial cell proliferation in duodenal and colonic crypts in fasted rats. Gastroenterology. 1976 Dec;71(6):1117–1120. [PubMed] [Google Scholar]
- Maurer H. R. Potential pitfalls of [3H]thymidine techniques to measure cell proliferation. Cell Tissue Kinet. 1981 Mar;14(2):111–120. doi: 10.1111/j.1365-2184.1981.tb00516.x. [DOI] [PubMed] [Google Scholar]
- Mayston P. D., Barrowman J. A., Dowling R. H. Effect of pentagastrin on small bowel structure and function in the rat. Digestion. 1975;12(2):78–84. doi: 10.1159/000197657. [DOI] [PubMed] [Google Scholar]
- Merchant J. L., Demediuk B., Brand S. J. A GC-rich element confers epidermal growth factor responsiveness to transcription from the gastrin promoter. Mol Cell Biol. 1991 May;11(5):2686–2696. doi: 10.1128/mcb.11.5.2686. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oscarson J. E., Veen H. F., Williamson R. C., Ross J. S., Malt R. A. Compensatory postresectional hyperplasia and starvation atrophy in small bowel: dissociation from endogenous gastrin levels. Gastroenterology. 1977 May;72(5 Pt 1):890–895. [PubMed] [Google Scholar]
- Penman I. D., el-Omar E., McGregor J. R., Hillan K. J., O'Dwyer P. J., McColl K. E. Omeprazole inhibits colorectal carcinogenesis induced by azoxymethane in rats. Gut. 1993 Nov;34(11):1559–1565. doi: 10.1136/gut.34.11.1559. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Preston-Martin S., Pike M. C., Ross R. K., Jones P. A., Henderson B. E. Increased cell division as a cause of human cancer. Cancer Res. 1990 Dec 1;50(23):7415–7421. [PubMed] [Google Scholar]
- Sagor G. R., Ghatei M. A., Al-Mukhtar M. Y., Wright N. A., Bloom S. R. Evidence for a humoral mechanism after small intestinal resection. Exclusion of gastrin but not enteroglucagon. Gastroenterology. 1983 May;84(5 Pt 1):902–906. [PubMed] [Google Scholar]
- Sobhani I., Lehy T., Laurent-Puig P., Cadiot G., Ruszniewski P., Mignon M. Chronic endogenous hypergastrinemia in humans: evidence for a mitogenic effect on the colonic mucosa. Gastroenterology. 1993 Jul;105(1):22–30. doi: 10.1016/0016-5085(93)90006-x. [DOI] [PubMed] [Google Scholar]
- Solomon T. E. Trophic effects of pentagastrin on gastrointestinal tract in fed and fasted rats. Gastroenterology. 1986 Jul;91(1):108–116. doi: 10.1016/0016-5085(86)90446-4. [DOI] [PubMed] [Google Scholar]
- Tatsuta M., Yamamura H., Iishi H., Noguchi S., Ichii M., Taniguchi H. Gastrin has no promoting effect on chemically induced colonic tumors in Wistar rats. Eur J Cancer Clin Oncol. 1985 Jun;21(6):741–744. doi: 10.1016/0277-5379(85)90272-x. [DOI] [PubMed] [Google Scholar]
- Tielemans Y., Håkanson R., Sundler F., Willems G. Proliferation of enterochromaffinlike cells in omeprazole-treated hypergastrinemic rats. Gastroenterology. 1989 Mar;96(3):723–729. [PubMed] [Google Scholar]
- Walsh J. H. Role of gastrin as a trophic hormone. Digestion. 1990;47 (Suppl 1):11–52. doi: 10.1159/000200509. [DOI] [PubMed] [Google Scholar]
- Watson S., Durrant L., Morris D. Gastrin: growth enhancing effects on human gastric and colonic tumour cells. Br J Cancer. 1989 Apr;59(4):554–558. doi: 10.1038/bjc.1989.112. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Willems G., Vansteenkiste Y., Limbosch J. M. Stimulating effect of gastrin on cell proliferation kinetics in canine fundic mucosa. Gastroenterology. 1972 Apr;62(4):583–589. [PubMed] [Google Scholar]
- Willems G., Vansteenkiste Y. Resistance of the antral mucosa to the trophic effect of gastrin in the dog. Biol Gastroenterol (Paris) 1974 Jul-Aug;7(3):237–240. [PubMed] [Google Scholar]
- Winsett O. E., Townsend C. M., Jr, Glass E. J., Thompson J. C. Gastrin stimulates growth of colon cancer. Surgery. 1986 Mar;99(3):302–307. [PubMed] [Google Scholar]
- Wong K., Beardshall K., Waters C. M., Calam J., Poston G. J. Postprandial hypergastrinaemia in patients with colorectal cancer. Gut. 1991 Nov;32(11):1352–1354. doi: 10.1136/gut.32.11.1352. [DOI] [PMC free article] [PubMed] [Google Scholar]