ISSN:0012-2823    

DOI:10.1159/000199346

出版商:S. Karger AG    

年代:1986

数据来源: Karger

ISSN:0012-2823    

DOI:10.1159/000199347

出版商:S. Karger AG    

年代:1986

数据来源: Karger

ISSN:0012-2823    

DOI:10.1159/000318062

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

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 sid

ISSN:0012-2823    

DOI:10.1159/000199380

出版商:S. Karger AG    

年代:1986

数据来源: Karger

ISSN:0012-2823    

DOI:10.1159/000318063

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Small intramucosal tumours in the oxyntic area of the rat stomach were observed in an oncogenicity study with omeprazole. The tumours could be defined as carcinoids of enterochromaffin-like (ECL) cell origin. ECL cells occur exclusively in oxyntic mucosa and respond to the trophic hormone gastrin with a proliferation that becomes exaggerated in old rats. Inhibition of gastric acid secretion is known to induce hypergastrinaemia in rats. According to the common concept of endocrine cells, a sustained hormonal stimulation with gastrin may induce a continuous gradient between hyperplasia and neoplasia of the ECL cells. The tumours found are thus to be regarded as hormone-induced endocrine tumours of the ECL cells in the stomach. The ECL-cell tumours of the rats in the oncogenicity study appeared to belong to the low-malignancy type of carcinoids and did not make their appearance until the end-life period of the study. The sex and species differences observed may be explained by inherent differences in gastrin response, spontaneous ECL cell density or in responsiveness to gastrin-stimulated ECL cell proliferation between sexes and species.

ISSN:0012-2823    

DOI:10.1159/000199381

出版商:S. Karger AG    

年代:1986

数据来源: Karger

ISSN:0012-2823    

DOI:10.1159/000318064

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The availability of potent and long-acting blockers of acid secretion, such as omeprazole, has paved the way for experimental studies on the long-term effects of permanently raised levels of circulating gastrin without the complication of surgical intervention. We have examined rats given high doses of the antisecretagogues omeprazole and ranitidine during 10 or 20 weeks for general trophic effects on the gastrointestinal tract and pancreas and for the effects on endocrine cells such as the somatostatin cells and the enterochromaffin-like (ECL) cells, which are present in the oxyntic mucosa. The ECL cells, which in the rat produce and store histamine (in addition to an as yet unidentified peptide hormone), are known to be activated by gastrin. In rats given high doses of omeprazole, the serum gastrin levels rose about 10-fold. General trophic effects were restricted to the stomach; the weight was increased, as was the thickness of the oxyntic mucosa. Omeprazole treatment resulted in a 3-to 5-fold increase in the ECL cell density. A close correlation was found between plasma gastrin levels and the ECL cell density as well as the levels of histidine decarboxylase and histamine in the oxyntic mucosa. The somatostatin cell density was unaffected by the hypergastrinemia. During a 10-week recovery period after discontinuation of the omeprazole treatment, the ECL cell density diminished, but was still significantly higher than in age-matched control rats. Plasma gastrin levels and gastric histidine decarboxylase activity rapidly returned to control values. The results suggest that the observed general trophic effects on the oxyntic mucosa and on the ECL cells are related to the plasma gastrin levels and not to an action of the antisecretagogues per se.

ISSN:0012-2823    

DOI:10.1159/000199382

出版商:S. Karger AG    

年代:1986

数据来源: Karger

ISSN:0012-2823    

DOI:10.1159/000199348

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Gastric acid secretion is known to be controlled by a complex system of interacting factors. Amongst these, regulatory peptides make a significant contribution. In the present study, immunocytochemistry and radioimmunoassay were used to investigate gastric regulatory peptides in animals with pharmacologically reduced gastric acid secretion. Increased numbers of densely immunostained antral gastrin-immunoreactive (G) cells were seen in rats which had been rendered virtually achlorhydric by administration of high-dose (400 μmol/kg daily) omeprazole over a 10-week period. These morphological changes were accompanied by increases in the plasma, antral and fundic concentrations of gastrin, as measured by radioimmunoassay. In contrast, antral somatostatin-containing cells were reduced, and there was a corresponding fall in the tissue content of the peptide. Ten weeks after treatment had ceased, the peptide profiles had returned to normal. No other regulatory peptide, whether endocrine or neural, appeared to alter during treatment with high-dose omeprazole. Treatment with high-dose (700 μmol/kg daily) ranitidine also caused an elevation in the G cell population and the antral and plasma content of gastrin, but to a lesser extent than that observed during omeprazole treatment. Somatostatin cells and tissue levels did not alter in these animals, and no other morphological changes could be detected. Radioimmunoassay, however, measured reduced quantities of vasoactive intestinal peptide, peptide histidine isoleucine and calcitonin gene-related peptide. Achlorhydria, induced by omeprazole at a dosage of 250–500 times that required for effective acid inhibition in man and animals, therefore resulted in reciprocal changes in gastrin and somatostatin cells. These changes are support for the postulated roles of these peptides in the control of gastric acid secret

ISSN:0012-2823    

DOI:10.1159/000199383

出版商:S. Karger AG    

年代:1986

数据来源: Karger