Activation and Hyperplasia of Gastrin and Enterochromaffin-Like Cells in the Stomach

Abstract

The stomach is rich in endocrine cells, most of which are still unidentified with respect to the peptide hormones they produce. The endocrine cell populations in the antrum usually differ from those in the oxyntic mucosa. Gastrin cells are found in the antrum and respond readily to stimuli from the gastric lumen, such as changes in the pH and the presence of food. In order to study the functional control of the antral gastrin cell, rats were subjected to different kinds of surgery. The serum gastrin concentrations in the various experimental groups were measured 8–10 weeks after the operations. Elevated antral pH raised the serum gastrin concentration. The combination of elevated antral pH and the passage of food over the pyloric glands produced gastrin cell hyperplasia. The operation that was most effective in inducing gastrin cell hyperplasia was removal of the acid-producing part of the stomach. Interestingly, gastrin cell hyperplasia was seen also after bilateral truncal vagotomy, indicating that an intact vagal innervation is not essential for the development of gastrin cell hyperplasia. Enterochromaffin-like (ECL) cells are endocrine/paracrine cells that are numerous in the acid-producing part of the stomach in many species. In the rat, they occur predominantly in the basal half of the oxyntic mucosa and produce and store histamine. The ECL cells have an unknown function and do not seem to respond to stimuli from the gastric lumen. They are activated by circulating gastrin and by vagal excitation. Gastrin mobilises histamine from these cells and activates the histamine-forming enzyme, histidine decarboxylase. Long-term hypergastrinaemia produces diffuse ECL cell hyperplasia, whereas hypogastrinaemia (following removal of the endogenous stores of gastrin by antrectomy) reduces the ECL cell number. Portacaval shunt brings about a marked increase in the number of ECL cells through an unknown mechanism. Also neuronal stimuli are important for the trophic control of the ECL cells. Studies of unilaterally vagotomised rats showed reduced weight and thickness of the oxyntic mucosa as well as a markedly reduced number of ECL cells on the denervated side.

Gastric Enterochromaffin-Like Cell Hyperplasia and Neoplasia in the Rat: An Indirect Effect of the Histamine H2-Receptor Antagonist, BL-6341

“…Nuclei contained prominent nucleoli and wellstained chromatin, but were otherwise unremarkable. These findings are consistent with those described for ECL cells in rats (20,22,26) and in man Although there were no carcinoid tumors at 55 mg/kg of BL-6341 or in the rats receiving the reference compound (cimetidine at 950 mglkg), proliferations of argyrophil endocrine cells could be detected in these groups at both 1 and 2 years by use of appropriate silver stains. At 1 year, the argyrophil endocrine cell increase was significantly greater than in controls at both 300 and 55 mg/kg of BL-6341 (Table 11).…”

“…The results of these silver stains, especially the Sevier-Munger technique, suggested that the carcinoid tumors were composed of enterochromaffinlike (ECL) cells (20,22,23). The immunoperoxidase technique demonstrated the presence of histamine in the proliferated endocrine cells in the fundic mucosa.…”

“…The immunoperoxidase technique demonstrated the presence of histamine in the proliferated endocrine cells in the fundic mucosa. The ECL cell is the only gastric endocrine cell in the rat stomach that contains histamine (22,23), and these cells are found exclusively in the fundic (owntic) mucosa;…”

Omeprazole: Its Influence on Gastric Acid Secretion, Gastrin and ECL Cells

“…These cells seem to be regulated by gastrin, both with respect to activity, reflected in their capacity to produce and release histamine, and to rate of proliferation. 'After various types of surgical interventions in the stomach in the rat, leading to changes in the plasma levels of gastrin, a causal relationship between circulating gastrin levels and the density of ECL cells in the oxyntic mucosa was postulated by Hdkanson and coworkers (9). Such a relationship was also evident during omeprazole and ranitidine treatments (see below).…”

“…Their function is unknown, in the sense that the peptide hormone they produce has not yet been identified. However, the ECL cells are active in the production and storage of histamine and are known to be under the control of gastrin (9). Based on this knowledge, it is not surprising that long-term (2 years) treatment of rats with potent long-acting inhibitors ofgastric acid 267 (20 nmol x kg-I x hour-') and carbachol(l10 nmol x kg-l x hour-') for 2 hours.…”