Gastrin, the enterochromaffinlike cell, and gastric tumors.
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Cell Transformation, Neoplastic↗
Biomedical subjects
E Brenna
Publications and source records attributed to E Brenna.
Effect of nicotine on the enterochromaffin like cells of the oxyntic mucosa of the rat.
Smoking has an unfavourable effect on peptic ulcer disease. The pathophysiological mechanisms underlying this effect are not known. The enterochromaffin like (ECL) cell is the cellular source of histamine participating in the regulation of acid secretion. The ECL cell is under functional and trophic control of gastrin and the vagus nerves. Nicotine may affect acid secretion through vagal pathways. Furthermore, nicotine may also stimulate neuroendocrine cells. The present study examined if chronic nicotine administration could stimulate the function and growth of the ECL cell. Rats inhaled nicotine vapour at a concentration of approximately 6.2 mumol/m3, 20 hours/day, 5 days/week for 11 weeks. Steady state plasma nicotine concentration was 461.8 (137.5 (SD)) nmol/l. The ECL cell density, histamine content and histidine decarboxylase activity of the oxynitic mucosa were similar to the controls. We also examined the effect of acute nicotine stimulation on the acid output and histamine release from the totally isolated vascularly perfused rat stomach. Nicotine did not stimulate acid secretion or histamine release. Thus no evidence could be provided to support the hypothesis that nicotine exerts its negative effects on peptic ulcer disease by stimulating the ECL cell.
Administration, Inhalation↗
Review article: the use of gastric acid-inhibitory drugs--physiological and pathophysiological considerations.
All vertebrates secrete gastric acid. Acid denatures the proteins in the food and thus makes them more accessible to proteolytic enzymes, and it kills swallowed micro-organisms. Gastric acid plays an important pathogenetic role in peptic ulcer disease and reflux oesophagitis. In these diseases, drugs that inhibit secretion of gastric acid will heal the lesions and suppress the symptoms. However, both reflux oesophagitis and peptic ulcer tend to recur when the acid-inhibitory treatment is stopped. Therefore, these patients often require long-term treatment with acid-inhibitors. In this overview the potential risks of long-term profound inhibition of acid secretion, raising the pH above 4 for a considerable time, resulting in reduced killing of micro-organisms and secondary hypergastrinaemia, are discussed. Gastrin regulates both the function (production and release of histamine) and growth of the enterochromaffin-like (ECL) cell. Hitherto, the role that this cell plays in gastric carcinogenesis appears to have been underestimated.
Animals↗
Calcium mediates gastrin-induced gastric histamine release in the rat.
This study examined the second messenger system responsible for gastrin-induced histamine release from the rat stomach. We examined the effect of different concentrations of ionized calcium, the calcium-channel blockers verapamil and nicardipine, and the intracellular calcium-chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxymethyl ester (BAPTA/AM) on gastrin-stimulated histamine release in the totally isolated vascularly perfused rat stomach. Moreover, the effect on baseline histamine release of caffeine as well as of forskolin and 3-isobutyl-1-methylxanthine (IBMX) was tested. Gastrin induced an immediate 10- to 15-fold increase in venous histamine. Perfusate ionized calcium in the 0.25-1.25 mM range did not affect histamine release; histamine release was attenuated by the 0.00 and 1.75 mM calcium concentrations. Verapamil, nicardipine, and BAPTA/AM inhibited gastrin-stimulated histamine release. Caffeine stimulated the release, whereas forskolin and IBMX had no effect. We conclude that gastrin-induced histamine release from the rat stomach is mediated by calcium, probably both from the intracellular pool and by transmembrane flux from the extracellular space.
Animals↗
The intensity and variability of symptoms in dyspepsia.
During the waiting time for upper gastrointestinal endoscopy 165 patients with dyspepsia completed a questionnaire and a diary for daily measurements of the symptoms pain, heartburn, and global complaints. 23 patients (14%) had peptic ulcer disease (PUD), 18 oesophagitis (11%), and the rest were labelled nonulcer dyspepsia (NUD). NUD was further subdivided into ulcer-like, reflux-like, dysmotility, and essential NUD by means of predefined symptom profiles. 39 (24%) patients were on H2 receptor antagonist treatment. In general, the intensity of the daily symptoms was rather low, and except for a higher rating of heartburn in oesophagitis, there were no significant differences between PUD, oesophagitis, and NUD--treated or untreated. NUD patients with reflux-like dyspepsia had significantly more heartburn than the group with essential NUD; otherwise there were no differences between the subgroups of NUD. The individual daily ratings for abdominal pain, heartburn, and global symptoms varied by an average standard deviation of 64%, 97% and 47% of the mean values, respectively, and were independent of treatment or diagnoses. There was an approximately 40% probability that two successive days had different levels of symptoms. Only 10% of the patients showed stable symptoms, and the patients were completely symptom-free for 20% of the observation period. Symptoms in dyspepsia patients disclosed low intensity and high variability in this study. Such factors may be important sources of bias in clinical trials.
Adolescent↗
The enterochromaffin-like (ECL) cell. Physiological and pathophysiological role.
Histamine has a central role in the regulation of gastric acid secretion. This histamine is produced by and released from the enterochromaffin-like (ECL) cell which accordingly has a key-regulatory role in the oxyntic mucosa. Gastrin and the vagal nerves stimulate the formation and release of histamine from the ECL cell. Moreover, gastrin and the vagal nerves also stimulate the proliferation of the ECL cell. An increased ECL cell density may partly explain the increased acid secretion in patients with duodenal ulcer, particularly in patients with Zollinger-Ellison syndrome. The reduced potency of histamine-2 blockers in patients with Zollinger-Ellison syndrome is probably due to increased histamine release by an elevated ECL cell mass. Prolonged and profound hypergastrinemia may lead to ECLomas. Moreover, a proportion of diffuse gastric carcinomas may originate from ECL cells.
Animals↗
Effects on the rat oxyntic mucosa of the histamine2-antagonist loxtidine and the H+, K(+)-ATPase inhibitor omeprazole.
The present study examined whether histamine could affect the growth of the enterochromaffin-like (ECL) cell and the parietal cell. The effects of the unsurmountable histamine H2-receptor antagonist loxtidine (80 mg/kg) and the H+, K(+)-ATPase inhibitor omeprazole (100 mumol/kg) were compared in female Sprague-Dawley rats. Both drugs were given by gavage once daily for 3 months. Omeprazole induced a more pronounced and sustained hypergastrinaemia than loxtidine. In spite of marked hypergastrinaemia during most of the day, even in the loxtidine-treated rats, the weights of the stomach and oxyntic mucosa were elevated only in the omeprazole-treated rats. The ECL cell density was slightly higher in the loxtidine- than in the omeprazole-treated rats. Both treatments elevated the gastrin-stimulated histamine release from the vascularly perfused stomach. The parietal cell density was unaffected by omeprazole treatment, whereas it tended to be reduced in the loxtidine-treated rats. Simultaneous administration of loxtidine and omeprazole reduced the sustained hypergastrinaemia induced by omeprazole given alone. The present study may indicate that histamine inhibits the growth of the ECL cell, but further studies are needed to elucidate if histamine has any trophic effect on the parietal cells.
Animals↗
Trophic effect of gastrin on the enterochromaffin like cells of the rat stomach: establishment of a dose response relationship.
Gastrin was given to rats by continuous subcutaneous infusion through implanted osmotic minipumps in doses covering a wide range of the dose response relationship for gastrin with regard to the trophic effect on the enterochromaffin like cells of the oxyntic mucosa. Thirty five rats were divided into five groups (each of seven rats), one group receiving a control solution of 1% albumin, the others receiving gastrin in 1% albumin at doses of 2.5, 5, 10, and 15 micrograms/kg/h, respectively. The plasma gastrin concentrations in the various groups increased in the same order of magnitude as expected from the gastrin doses given. Gastrin induced a dose dependent increase in enterochromaffin like cell density, oxyntic mucosal histamine concentration and histidine decarboxylase activity up to the dose of 5 micrograms/kg/h, where the increase levelled off. Hence, the dose response relationship for the trophic effect of gastrin on the enterochromaffin like cells seems to follow a polynomial rather than a linear function. These findings may also contribute to the understanding of the trophic effect of gastrin on enterochromaffin like cells in man with conditions associated with hypergastrinaemia.
Animals↗
Gastrin-histamine sequence in the regulation of gastric acid secretion.
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Animals↗
Relationship between endoscopic hiatus hernia and gastroesophageal reflux symptoms.
Little is known about the relationship between hiatus hernia (HH) and gastroesophageal reflux symptoms (GERS). Nine hundred and thirty patients submitted to gastroscopy because of symptoms completed a self-administered questionnaire. Fourteen per cent showed esophagitis (ES) and 17% HH. Forty-nine per cent of the patients with HH had endoscopic ES, and 60% of those with ES had HH. The severity of ES was dependent (p less than 0.05) on both the presence and the size of HH. After exclusion of patients with peptic ulcer and malignancy, patients with and without HH and ES were compared with regard to the presence of single symptoms and a weighted GERS score based on symptoms proven to be typical for ES. Only borderline differences were found between patients with ES and HH and those with ES and no HH. The former group, however, presented with significantly (p less than 0.001) more GERS than the patients with HH only. Nevertheless, the patients with HH as the only pathologic finding had significantly (p less than 0.01) more GERS than the patients with no major endoscopic abnormality. This study indicates a close association between HH and gastroesophageal reflux disease and supports the clinical significance of an endoscopically detected HH.
Adult↗
Effect of the histamine-1 antagonist astemizole alone or with omeprazole on rat gastric mucosa.
The stimulation of acid secretion by gastrin may in the rat be explained solely by gastrin-induced histamine release. This study was done to examine whether histamine could mediate the general trophic effect of gastrin on the oxyntic mucosa, by using a long-acting selective histamine-1 antagonist (astemizole) alone or with omeprazole-induced hypergastrinaemia for 90 days in female Sprague-Dawley rats. At day 90, isolated vascularly perfused rat stomachs were prepared to study maximal gastrin- and histamine-stimulated acid and pepsinogen outputs and maximal gastrin-stimulated histamine release. Oxyntic mucosa morphometry, mucosal histamine and pepsinogen contents, and plasma gastrin and histamine levels were also determined. For the first time, omeprazole has been found to inhibit gastric emptying and to increase plasma histamine. As compared with controls, astemizole alone did not influence plasma gastrin, increased plasma histamine in only some rats, and gave a slight increase in all other variables. Together with omeprazole, it further increased variables already stimulated by omeprazole. Thus, mucosal thickness, histamine concentration, and chief-cell density in oxyntic mucosa were significantly higher in astemizole/omeprazole-treated rats than in omeprazole-treated rats. Gastrin-stimulated histamine release was increased in both astemizole- and omeprazole-treated rats. For all rats plasma histamine was significantly correlated with plasma gastrin and with numerical fundic argyrophil cell density. In conclusion, the present study confirms the trophic effect of gastrin and shows a slight trophic effect of astemizole on the oxyntic mucosa. It also shows that plasma histamine may reflect the argyrophil cell density in the oxyntic mucosa and that omeprazole inhibits gastric emptying.
Animals↗
Studies of isolated parietal and enterochromaffin-like cells from the rat.
Rat gastric mucosal cells isolated by enzyme dispersion were separated by elutriation centrifugation. The amount of histamine and the number of enterochromaffin-like (ECL) cells and parietal cells were determined in the crude mucosal cells and the various elutriation fractions. The mucosal cells contained 2.6% ECL and 20% parietal cells. Elutriation centrifugation resulted in good separation of parietal cells and ECL cells. Most of the ECL cells were elutriated in the small cell fractions. Scattered ECL cells were also present in the fraction enriched with parietal cells. Histamine and carbacholine stimulated aminopyrine uptake in a concentration-dependent manner with about the same efficacy, 5.6 times the base-line value. When combined with the phosphodiesterase inhibitor isobutyl methylxanthine, the maximal histamine stimulation was increased to 16.8 times the base-line value, and the sensitivity increased about 10-fold. Gastrin at high and unphysiologic concentrations stimulated only faintly the aminopyrine uptake in parietal cells and the histamine release from ECL cells.
1-Methyl-3-isobutylxanthine↗
The effect of omeprazole-induced hypergastrinemia on the oxyntic mucosa of mastomys.
Mastomys is a rodent with a high incidence of spontaneous carcinoids in the acid-producing part of the stomach. The present study was conducted to examine whether hypergastrinemia could promote tumor formation in this species. Mastomys, 4 months of age, were treated for 5 months with omeprazole subcutaneously, 100 mumol/kg body weight daily, and compared with mastomys given the vehicle only. The plasma gastrin concentration and the number of antral gastrin cells were increased in the omeprazole-treated group. The hypergastrinemia was associated with elevated histidine decarboxylase activity and histamine content in the oxyntic mucosa and with a trophic effect on the oxyntic mucosa and the enterochromaffin-like cells. However, no carcinoid tumors were observed, possibly because the strain of mastomys studied does not produce carcinoids spontaneously.
Animals↗
Radioimmunoassay of histamine.
Histamine is formed by decarboxylation of the amino acid histidine and is found both in plants and in animals, including man. In man it has important biologic functions. To assess the physiologic role of histamine, however, it is necessary to have a reliable and convenient method to determine its concentration in biologic fluids and tissue. Histamine has been determined by bioassay, chemically by different modification of a fluorometric method, by radioenzymatic methods, and, recently, by immunoassays. Immunoassay of histamine has, however, been difficult to establish, mainly as a result of problems with the production of an antibody with histamine specificity. This is due to the general occurrence of histamine in all animal species. By binding histamine to different ligands, several researchers have succeeded in producing antibodies against antigens in which histamine is integrated. Treating samples and histamine standard with the same coupling agent, reliable and specific radioimmunoassays of histamine have been established. We have for some years utilized a commercial radioimmunoassay of histamine and confirmed its convenience, specificity, and sensitivity. In some patients taking a histamine-2 blocker (cimetidine or ranitidine) we have detected an increase in plasma histamine which also tended to be increased after proximal gastric vagotomy and in patients with gastric ulcer compared with patients with duodenal ulcer. In rats treated with high doses of omeprazole for 90 days we found an increase in the enterochromaffin-like cell mass and in histamine concentration in the oxyntic mucosa which was reflected by an increase in plasma histamine.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Trophic effect of histamine on the stomach.
On the basis of clinical observations and experimental animal studies it has been established that gastrin has a trophic effect on the oxyntic mucosa. On the other hand, histamine, being at least as efficient as gastrin as an acid secretagogue, has experimentally been reported not to have such trophic effect. However, during the last few years both endogenously and exogenously induced hypergastremia have been shown to have a specific trophic effect on the enterochromaffin-like (ECL) cell and a less pronounced and later detectable general trophic effect on the oxyntic mucosa. Moreover, in the rat (the species in which most of the trophic studies have been done) the acid-stimulatory effect of gastrin may be solely explained by stimulation of histamine release from ECL cells. Therefore, it seemed natural to evaluate whether the general trophic effect of gastrin could also be caused by histamine or another substance released from the ECL cells. In this review we challenge the concept that maximal pentagastrin-stimulated acid secretion only reflects the parietal cell mass, since the acid-stimulatory effect of gastrin is mediated by histamine release. Therefore, maximal pentagastrin-stimulated acid secretion reflects both the ECL cell mass and the parietal cell mass. With regard to the possible trophic effect of histamine, we show that the doses previously used have been inadequate. Furthermore, histamine has been reported to have a trophic effect on the parietal cell in the dog; some patients with hyperhistaminemia have an increased maximal histamine-stimulated acid secretion, suggesting an increase in the parietal cell mass; and there is parietal cell hyperplasia in the oxyntic mucosa surrounding the histamine-producing carcinoids in mastomys.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Role of the enterochromaffin-like cells and histamine in the regulation of gastric acid secretion].
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Acetylcholine↗
The predictive value of history in dyspepsia.
Symptomatic patients referred to an open-access upper gastrointestinal endoscopy completed a detailed, self-administered questionnaire aimed at assessing the predictive value of history in dyspepsia. Nine hundred and thirty patients were suitable for analysis. Of these, 29% were found to have organic dyspepsia. A substantial overlap of symptoms and demographic data was found among the various endoscopic diagnoses. Discriminating variables were identified by stepwise logistic regression analysis and included in predictive score models. Pain relieved by antacids, age above 40 years, previous peptic ulcer disease, male sex, symptoms provoked by berries, and night pain relieved by antacids and food were found to predict organic dyspepsia with a sensitivity and specificity of approximately 70%, when applied on the observed material. Similar probabilities were found for score models of peptic ulcer and esophagitis. In general, the low prevalence of organic diseases resulted in low positive and high negative predictive values. Accordingly, the main impact of the predictive models may be to reduce the number of negative endoscopies rather than to predict a precise diagnosis. Independent of disease category and age, 41% of the subjects expressed a fear of malignancy, emphasizing the value of reassurance from a negative endoscopy.
Adult↗
The benefit of colonoscopy.
In a prospective study involving 833 consecutive outpatient and open-access colonoscopies, attempts were made to characterize the benefit of colonoscopy in terms of both predicted and unpredicted findings and therapeutic procedures. The endoscopist therefore predicted the endoscopic findings before the endoscopy. The results were compared for the different indications for colonoscopy. The overall agreement between the predictions and the colonoscopic findings was 61%. Clinically significant abnormalities were found in about half the examinations. The most frequent abnormal findings were benign polyps (24%), inflammatory bowel disease (17%), and malignancy (5%). In about half the patients with a malignancy the indication for colonoscopy was rectal bleeding, and half of the malignancies were not predicted. The greatest benefit of colonoscopy was found in patients referred because of overt rectal bleeding or occult faecal blood, and abnormal barium enema or endoscopy findings. The importance of complete colonoscopy in connection with operation for colorectal carcinoma is emphasized.
Colonic Polyps↗