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Background: Concanavalin-A, the lectin present in Jack beans, binds to mannose- and glucose-containing residues and can interact with the epidermal growth factor receptor and moderate cell proliferation in vitro., Aim: To compare the actions of concanavalin-A and epidermal growth factor on the gastrointestinal tract in vivo., Methods: Rats maintained on total parenteral nutrition were given intragastric concanavalin-A, intravenous epidermal growth factor or concanavalin-A and epidermal growth factor. Cell proliferation and crypt fission were assayed in 'micro-dissected' crypts., Results: Concanavalin-A and epidermal growth factor both significantly elevated proliferation in the small intestine and colon. No significant interaction between the effects of these two agents was seen, except in the mid small intestine where there was a synergistic interaction. Concanavalin-A had no effect on crypt branching. Epidermal growth factor significantly reduced branching in the distal small intestine and mid colon., Conclusion: The effects of the two agents appeared to be separate, except in the mid small intestine where they were additive. This is in marked contrast with the actions reported in vitro, where concanavalin-A is a powerful inhibitor of epidermal growth factor-induced cell proliferation. Concanavalin-A thus has potential for enhancing the functions of the small intestine.

Background: Ingested peanut agglutinin stimulates colonic proliferation in humans. In rats, ingested peanut agglutinin stimulates hormone release and proliferation in the small and large intestines. Peanut agglutinin is absorbed into the circulation but little is known about the systemic effect of this lectin. Therefore, we studied the effect of intravenous peanut agglutinin on hormone release and intestinal growth., Method: Six rats per group received peanut agglutinin infusion at 0, 2, 20 or 200 microg/rat/day for 6 days via the right jugular vein. Organ weights were measured, pancreatic enzymes, DNA, RNA and protein levels were analysed. Plasma hormones were measured by radioimmunoassay. All tissues were examined histologically. Small intestinal and colonic proliferation rates were estimated by metaphase arrest., Results: High-dose peanut agglutinin significantly reduced the wet weight of the stomach by 7% (P < 0.05) and large intestine by 10% (P < 0.05). Peanut agglutinin dose-dependently released enteroglucagon; low-, medium- and high-dose by 64%, 126% (P < 0.01) and 180% (P < 0.01), respectively, and glucagon-like peptide-1 by 127% (P < 0.01), 169% (P < 0.01) and 315% (P < 0.001), respectively. Peanut agglutinin had no effect on cholesystokinin, gastrin or insulin levels. Peanut agglutinin, low-, medium- and high-dose stimulated proliferation in the mid colon by 42% (P < 0.01), 30% and 38%, respectively. Only high-dose peanut agglutinin stimulated proliferation in the distal colon by 54% (P < 0.01). No histological changes were evident in any tissue., Conclusion: Intravenous peanut agglutinin released hormones and stimulated colonic proliferation. Proliferation of the small intestine seen after ingestion of peanut agglutinin in previous studies appears to require luminal contact between enterocytes and the lectin. Possible clinical applications include reversal of atrophy during total parenteral nutrition, anastomotic healing after surgery and restoration of mucosa integrity in colitis.

Total parenteral nutrition (TPN) causes atrophy of gastrointestinal epithelia, so we asked whether lectins that stimulate epithelial proliferation can reverse this effect of TPN. Two lectins stimulate pancreatic proliferation by releasing CCK, so we asked whether lectins that stimulate gastrointestinal proliferation also release hormones that might mediate their effects. Six rats per group received continuous infusion of TPN and a once daily bolus dose of purified lectin (25 mg. rat-1. day-1) or vehicle alone (control group) for 4 days via an intragastric cannula. Proliferation rates were estimated by metaphase arrest, and hormones were measured by RIAs. Phytohemagglutinin (PHA) increased proliferation by 90% in the gastric fundus (P < 0.05), doubled proliferation in the small intestine (P < 0.001), and had a small effect in the midcolon (P < 0.05). Peanut agglutinin (PNA) had a minor trophic effect in the proximal small intestine (P < 0.05) and increased proliferation by 166% in the proximal colon (P < 0.001) and by 40% in the midcolon (P < 0.001). PNA elevated circulating gastrin and CCK by 97 (P < 0.05) and 81% (P < 0.01), respectively, and PHA elevated plasma enteroglucagon by 69% and CCK by 60% (both P < 0.05). Only wheat germ agglutinin increased the release of glucagon-like peptide-1 by 100% (P < 0.05). PHA and PNA consistently reverse the fall in gastrointestinal and pancreatic growth associated with TPN in rats. Both lectins stimulated the release of specific hormones that may have been responsible for the trophic effects. It is suggested that lectins could be used to prevent gastrointestinal atrophy during TPN. Their hormone-releasing effects might be involved.

Recombinant urogastrone (human epidermal growth factor) was infused into rats in which intestinal cell proliferation was reduced to a steady state basal level by feeding them intravenously. Urogastrone elevated the augmented metaphase index and weight of all sections of the gastrointestinal tract in a dose-related manner. Infusion of urogastrone at a dose which has a minimal effect on gastric acid secretion significantly increased crypt cell production and tissue weights throughout the gastrointestinal tract. Intravenous urogastrone was also effective in restoring cell proliferation after the intestine had become hypoproliferative. Urogastrone administered luminally had no significant effect on either intestinal weight, crypt cell production rate, or metaphase collection.

The effects of starvation and refeeding on intestinal cell proliferation at several sites of the rat gastrointestinal tract were studied and used as a model of altered cell proliferation in order to investigate the relationship between the rate of cell production and plasma gastrin and enteroglucagon. There was a marked fall in crypt cell production rate after four days starvation, with the proximal sites of the gut being most affected. The response to refeeding varied with site, suggesting that there was more than one mechanism for the control of intestinal cell proliferation. Plasma gastrin and enteroglucagon both fell to one fifth of their control level after starvation. Plasma gastrin increased slowly after refeeding, whilst plasma enteroglucagon increased rapidly to values significantly above control. Plasma gastrin was only correlated with crypt cell production in the duodenum, while plasma enteroglucagon was correlated with crypt cell production rate at several sites, indicating that enteroglucagon may be involved in the control of intestinal cell production.

The effects of starvation and refeeding on intestinal cell proliferation were studied in four sites of the mouse intestine. Control mice were studied at different times of day in order to compensate for any circadian variations in proliferation. A circadian rhythm in crypt cell production rate was observed in all the sites of the small intestine and colon, and this rhythm appeared to be entrained to the food intake. The fractional crypt cell production rate decreased in all sites of the intestine after 24 h starvation, and remained low until 9 h after refeeding, when there was a marked increase in the crypt cell production rate of all the small intestinal sites, especially the proximal sites. There was little change in colonic crypt cell production rate until 12 h after refeeding, when there was a large increase in cell production. The crypt cell production rate of all sites then returned to control values for the remainder of the investigation. Crypt cell number decreased after refeeding and villus cell number increased, however a similar effect was observed in the control animals, nevertheless the changes in villus cell population of the refed mice occurred before any increase in crypt cell production, suggesting that cell migration from crypt to villi is not immediately dependent on cell proliferation.

To find out whether non-steroidial anti-inflammatory drugs (NSAIDs) inhibit the proliferation of mucosal cells that normally leads to healing of gastric ulcers a microdissection technique was used to quantify mitosis in gastric glands at the ulcer edge in relation to that in the adjacent mucosa. The regeneration index thus obtained of the ulcer edge was greater in the 9 subjects with gastric ulcers not taking NSAIDs (mean index 3.1 [SEM 0.61]) than that in the 8 patients taking NSAIDs (index 1.49 [0.16]). In rats in which gastric ulcers were produced with a cryoprobe, the ulcers were larger and slower to heal in those receiving indomethacin than in controls; also, immunohistochemical staining indicated significantly fewer mitotic cells in glands adjacent to the ulcer in indomethacin-treated rats (8 mitoses [SEM 3]) than in control animals (25 [5]). The prostaglandin E1 analogue misoprostol reversed the inhibition of healing and substantially restored the proliferative rate in the animals. Inhibition of epithelial cell division normally involved in gastric ulcer healing would contribute to the high prevalence of gastric ulcer during NSAID therapy. [ABSTRACT FROM AUTHOR]