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SUMMARY1. Epidermal growth factor (EGF) infused subcutaneously in a dose of 10 ,g/kg . h but not 1 jug/kg . h inhibited spontaneous gastric acid and pepsin secretion, whereas when given intragastrically in a dose of 10 jug/kg . h it failed to affect this secretion.2. EGF injected intraperitoneally at 8 h intervals for 24 h significantly stimulated DNA synthesis in the gastroduodenal mucosa and the pancreas, whereas when administered intragastrically it stimulated DNA synthesis only in the gastroduodenal mucosa but not in the pancreas.3. Chronic parenteral administration of EGF significantly increased the DNA and RNA contents of the gastroduodenal mucosa and the pancreas.4. This study demonstrates that parenteral EGF is a potent inhibitor of gastric secretion and trophic agent for the gastroduodenal mucosa and pancreas, and that the gastric inhibitory and trophic effects of EGF are the results of two separate mechanisms.

Transforming growth factor alpha (TGF) and epidermal growth factor (EGF) present in the gastric mucosa are polypeptides with similar biologic activity. This study compares the activity of TGF and EGF in the protection against injury by 100% ethanol and stress and in healing of acute gastric ulcerations. TGF and EGF (12.5-100 micrograms/kg-h) infused subcutaneously 30 min before and during ethanol or stress decreased mucosal lesions dose-dependently. The ID50 for ethanol- and stress-induced lesions after TGF were 40 and 70 micrograms/kg-h and after EGF 60 and 100 micrograms/kg-h. TGF and EGF infused subcutaneously into intact rats inhibited gastric acid secretion but did not affect the gastric blood flow or mucosal generation of prostaglandin E2 (PGE2). Both TGF and EGF also significantly enhanced the healing of stress-induced lesions and the restoration of DNA synthesis. Ethanol and stress reduced blood flow in the oxyntic mucosa by 68% and 51%, respectively, and this effect was partially reversed by EGF and TGF. Pretreatment with indomethacin (5 mg/kg intraperitoneally), which reduced mucosal generation of PGE2 by 85%, decreased in part the protection by TGF and EGF against ethanol-induced damage and virtually abolished the protective action of these peptides against stress-induced injury.(ABSTRACT TRUNCATED AT 250 WORDS)

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Growth responses to endogenous and exogenous gastrin were examined in the pancreas and gastrointestinal tract mucosa. Rats were either antrectomized to remove the primary source of endogenous gastrin or subjected to a sham operation. Three weeks after surgery, half of the antrectomized animals were injected ip with pentagastrin (250 microgram/day) four times per day. Injections were carried out for a week. Antrectomy resulted in serum gastrin levels approximately one third of normal. DNA synthesis and DNA and RNA content of the pancreas and oxyntic gland, duodenal, and colonic mucosa were significantly reduced by antrectomy. In each case, pentagastrin treatment restored DNA synthesis and RNA and DNA levels to normal. Significant decreases in pancreatic and colonic weights in antrectomized animals were also completely prevented by pentagastrin injection. These results indicate that endogenous gastrin has an important role in the regulation of pancreatic and colonic mucosal growth, in addition to its already established similar function in oxyntic gland mucosa.

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The gastropathy associated with the ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin is a common side effect of this class of drugs, but the precise mechanisms by which they cause mucosal damage have not been fully explained. During continued use of an injurious substance, such as aspirin, the extent of gastric mucosal damage decreases and this phenomenon is named gastric adaptation. To assess the extent of mucosal damage by aspirin and subsequent adaptation the effects of 14 days of continuous, oral administration of aspirin (2 g per day) to eight healthy male volunteers was studied. To estimate the rate of mucosal damage, gastroscopy was performed before (day 0) and at days 3, 7, 14 of aspirin treatment. Gastric microbleeding and gastric mucosal blood flow were measured using laser Doppler flowmeter and mucosal biopsy specimens were taken for the estimation of tissue DNA synthesis and RNA and DNA concentration. In addition, the activation of neutrophils in peripheral blood was assessed by measuring their ability to associate with platelets. Aspirin induced acute damage mainly in gastric corpus, reaching at day 3 about 3.5 on the endoscopic Lanza score but lessened to about 15 at day 14 pointing to the occurrence of gastric adaptation. Mucosal blood flow increased at day 3 by about 50% in the gastric corpus and by 88% in the antrum. The in vitro DNA synthesis and RNA concentration, an index of mucosal growth, were reduced at day 3 but then increased to reach about 150% of initial value at the end of aspirin treatment. The gastric microbleeding rate rose from about 0-38 mi/day at day 0 to about 7-7 mi/day at day 3 but then decreased significantly to virtually normal values at the end of the study. The neutrophil/platelet adherence showed significant increase during aspirin treatment. It is concluded that the treatment with aspirin in humans induces gastric adaptation to this agent, which entails the increase in mucosal blood flow, the rise in neutrophil activation, and the enhancement in mucosal growth.