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Differentiation of the gastric mucosa. I. Role of histamine in control of function and integrity of oxyntic mucosa: understanding gastric physiology through disruption of targeted genes.

Many physiological functions of the stomach depend on an intact mucosal integrity; function reflects structure and vice versa. Histamine in the stomach is synthesized by histidine decarboxylase (HDC), stored in enterochromaffin-like (ECL) cells, and released in response to gastrin, acting on CCK(2) receptors on the ECL cells. Mobilized ECL cell histamine stimulates histamine H(2) receptors on the parietal cells, resulting in acid secretion. The parietal cells express H(2), M(3), and CCK(2) receptors and somatostatin sst(2) receptors. This review discusses the consequences of disrupting genes that are important for ECL cell histamine release and synthesis (HDC, gastrin, and CCK(2) receptor genes) and genes that are important for "cross-talk" between H(2) receptors and other receptors on the parietal cell (CCK(2), M(3), and sst(2) receptors). Such analysis may provide insight into the functional significance of gastric histamine.

Animals↗

Morphological, functional and immunological state of the gastric mucosa in gastric carcinoma families. Comparison with a computer-matched family sample.

Three hundred and one first-degree relatives (series) of 73 gastric carcinoma patients and 358 control relatives (controls) of 73 computer-matched probands from a general population were studied by direct-vision gastric biopsy and functional and immunological examinations. The controls were representative of the series with respect to age, sex, birth and dwelling place, and relationship of the relatives. Series and controls behaved similarly as to total prevalence of gastritis, age and sex distribution of gastritis, serum gastrin level, and circulating gastric antibodies. On the other hand, the total prevalence of hyperplastic polyps, atrophic gastritis of the body and antrum, severe atrophic gastritis of the body, intestinal metaplasia, epithelial atypia, and achlorhydria was significantly higher in the series than in the controls. In subjects below 50 years of age the prevalence of severe atrophic gastritis of the body, intestinal metaplasia, and epithelial atypia was also significantly higher in the series. In addition, the mean age of the subjects with atrophic gastritis, intestinal metaplasia, epithelial atypia, and achlorhydria was lower in the series than in controls; however, significant differences were found only in female subjects with epithelial atypia and atrophic gastritis of the body. The results suggest that the prevalence of signs often considered premalignant is significantly higher in carcinoma relatives than in controls and that these signs show a trend to occur at an earlier age in carcinoma relatives. This could explain the significantly higher than expected death rate from gastric carcinoma in close relatives with this disease, found in the present and in other series.

ABO Blood-Group System↗

Changes in glutathione in gastric mucosa of gastric ulcer patients.

To clarify the role of glutathione (GSH), an antioxidative substance, and its association with the gastric mucosal defense mechanism, we examined the gastric mucosal GSH and GSH-dependent enzymes in gastric ulcer patients. The subjects of this study were 10 patients with active ulcer on the lesser curvature side in the lower part of the gastric body and 11 normal controls. At the time of gastric endoscopy, gastric mucosal specimens were obtained by routine forceps biopsy from a site several millimeters apart from the ulcer margin, and these specimens were used for measurement of GSH, glutathione peroxidase (GSH-Px), glutathione-S transferase (GST) and gamma-glutamyl transpeptidase (gamma-GTP). The GSH level and the GSH-Px and GST activities in the patients with gastric ulcer were lower than those in the control group. The GSH-Px activity at the healed stage after treatment was increased compared with the pre-treatment value, while the GSH level was not markedly increased and the GST and gamma-GTP activities were similar to the pre-treatment value. The GSH level and GSH-Px activity remained decreased in the non-responder group. These results suggest that gastric mucosal GSH and GSH-dependent enzymes are closely related to the etiology and course of gastric ulcer.

Adult↗