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Administration of lysosomes and lysosome enzymes into the submucous base of intact rats' stomachs did not result in ulceration. Premedication by histamine, serotonin (combined and separated) and ACTH did not increase sensibility of mucous membrane to lysosome enzymes. Prednisolone-premedication provoked the decrease of mucous membrane resistance to free lysosome enzymes and appearance of ulcerative lesions in the point of enzyme applications. Free lysosome enzymes are able to produce ulcerative lesions. This process is going on with the participation of prednisolone.

In the experiments on Wistar rats we showed that administration of ulcerogenic drugs (cinchophen, acetylsalicylic acid, butadione, indomethacin etc.) produced the alterations of free activity of lysosomal enzymes in the homogenates of ulcerated stomachs, presumably the significant elevation of the activity of cathepsins (more often cathepsin with optimum of activity at pH 5.5) and the significant reduction of free activity of acid nucleases (more often of DNA-ase). The alterations of free activity of lysosomal enzymes were as in cases with gastric ulcerations as in cases with unaffected stomachs.

Free glutamine content and phosphate-dependent glutaminase activity were studied in the biopsy specimens from the tissue of ulcer, polyps, carcinoma and the surrounding gastric mucosa of patients with precancerous diseases and carcinoma of the stomach. The glutamine content in carcinoma was not significantly different from that in the normal gastric mucosa. The glutamine level in the gastric mucosa remote from the tumour was considerably higher than normal. In case of polyposis of the stomach glutamine was present in the polyps and absent in the remote gastric mucosa. A marked glutaminase activity was revealed in the carcinoma of the stomach, but its level did not differ from the normal or in the case of precancerous diseases.

Experiments were performed on white rats with experimental acetate ulcer of the stomach and intestine. At the height of destruction of gastric mucosa tissue (60 minutes from the onset of ulcer formation) a consistent increase in acid phosphatase secretion was recorded. This process was accompanied, as a rule, by significant elevation of proteolytic activity (pH 6.5-7.0) in tissue extract obtained from the affected area. It is suggested that the increased proteolytic activity observed at pH 6.5-7.0 in the tissue extract from the ulcerous area is most likely related to the release of lysosomal proteases at the height of tissue destruction. It thus appears that ulcer of the gastric mucosa induced by acetic acid application is determined by interstitial proteolytic activity of cathepsins that are released during the destruction of lysosomal membranes.

The method of Okabe was used to induce experimental gastric ulcer in rats. The content of serotonin and histamine was determined in gastric mucosa extracts. The spectrum of proteolytic enzymes and proteolytic activity in gastric mucosa extracts were determined by polyacrylamide gel disc electrophoresis at varying pH. It was found that in "acetate" gastric ulcer the rats had the increased content of serotonin in the gastric mucosa followed by the elevated histamine content. In the early stages of "acetate" ulcer the proteolytic activity was detectable at pH 6.5-7. At the same time there took place a reconstruction of the spectrum of proteolytic enzymes. Analogous changes in the spectrum of proteolytic enzymes of gastric mucosa extracts and occurrence of the proteolytic activity at pH 6.5-7 were also recorded after serotonin administration (30 mg/kg) to intact rats. Thus it has been demonstrated that the increased serotonin output is implicated in the changes seen in the enzymatic spectrum and in the occurrence of proteolytic activity at high pH (6.5-7). The latter might be related to the release of lysosomal proteases responsible for intratissular proteolysis in the gastric mucosa and for ulcer formation.

Disc-electrophoretic investigation of proteases of the gastric juice of dogs under normal conditions and in experimental atophan ulcer of the stomach demonstrated that in fasting dogs ulceration was accompanied by marked quantitative changes in the protease spectrum. Fraction No. 6 showed a significant elevation against the background of total reduction of proteolytic fraction of the gastric juice in sham feeding of ulcerated dogs. Sham feeding replete ulcerated dogs indicated a marked increase of fractions No.1 and No.2. The noted changes of the gastric juice protease spectrum may be of ulcerogenic significance.

Lysosomal membrane stability has been studied in the gastric mucosa in response to mechanical damage caused by lysosomal fractionation and release of lysosomal enzymes from mucous cells into the gastric cavity of alive animals during induction of acetic ulcer or erosive damage of the gastric mucosa resulting from intraperitoneal introduction of histamine and serotonin. It has been found that all types of ulcerogenesis in the gastric mucosa led to the decrease in lysosomal membrane stability to mechanical stress in the course of lysosomal fractionation. In addition there was a substantial release of lysosomal enzymes into the gastric cavity in different types of ulcerogenesis. The decrease in lysosomal membrane stability combined with a subsequent development of ulcers and erosions in the gastric mucosa seems indicative of the fact that lysosomal enzymes take part in the initial formation of ulcers in the gastric mucosa.