Evaluation of the Effects of Pentagastrin, Gastrin and Pancreatic Glucagon On Cell Proliferation In the Rat Gastrointestinal Tract

Abstract

The effects of 6 injections of a range of doses (100-1000 .mu.g/kg body wt) of pentagrastrin and single injection of a range of doses of porcine gastrin (10-40 .mu.g/kg body wt) and pancreatic glucagon (25-100 .mu.g/kg body wt) on cell proliferation in the intestine of fasted rats was investigated. The end-point employed included the measurement of 14C leucine incorporation and thymidine-derived tritium content of the body of the stomach, duodenum, jejunum, ileum and colon. The 14C and tritium content per .mu.g of tissue in triplicate samples of 50 individually dissected crypts of glands were determined. From these data and the wet weight of the washed, blotted, intestinal segments, values for crypts/.mu.g tissue and crypts/segment were calculated. The results demonstrated that pentagastrin at physiological doses decreased cell proliferation slightly in stomach, while gastrin and glucagon were without effect. In the small intestine, pentagastrin and gastrin were without significant effect with the exception that they increased the weight of the duodenum. In contrast, a high physiological dose of glucagon increased DNA and protein synthesis throughout the small bowel, but particularly in the ileum. Pharmacological doses of pentagastrin and all doses of gastrin appeared to increase cell proliferation in the colon although the possibility could not be excluded that this was due to stimulation of precursor uptake, Gastrin also increased colonic weight. Glucagon had no effects in the colon. These observations are compatible with the hypothesis that the primary effects of gastrin and pentagastrin on the proximal intestine are as secretogogues and effects on cell proliferation may be secondary, gastrin and pentagastrin at physiological levels do not stimulate small intestinal cell proliferation, (however, glucagon does) and gastrin at physiological levels and pentagastrin at pharmacological levels may stimulate cell proliferation in the colon.