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Biomedical subjects

A K Sandvik

Publications and source records attributed to A K Sandvik.

At least 73 records · Page 4Linked to original sources
PubMed1995

Effect of the histamine-2 agonist impromidine on stem cell proliferation of rat oxyntic mucosa.

BACKGROUND: The trophic effect of gastrin on the histamine-containing enterochromaffin-like cell is pronounced but on the stem cell of the oxyntic mucosa it is only modest. In the rat, gastrin stimulates acid secretion mainly by releasing histamine from enterochromaffin-like cells. This study was designed to test the hypothesis that the trophic effect of gastrin on stem cells is also mediated by histamine released from the enterochromaffin-like cell. METHODS: We stimulated rats with the histamine-2 agonist impromidine. Impromidine, 0.2 mg/h, was given for 2 days by subcutaneously implanted osmotic minipumps, and the trophic effect on stem cells was assessed by incorporation of tritiated thymidine. RESULTS: The plasma gastrin concentrations were 33.9 (9.4) pM and 27.3 (6.0) pM, and the stem cell labelling index values were 5.92 (1.94) and 8.09 (3.78) in the controls and impromidine-stimulated animals, respectively (mean value (SD)). These differences were not statistically significant. CONCLUSION: The present study provides no evidence that histamine-2 receptors mediate a trophic effect on the stem cell of the rat oxyntic mucosa.

Animals↗
PubMed1994

The effect of tripotassium dicitrato bismuthate on the rat stomach.

BACKGROUND: Bismuth has been used as symptomatic treatment of dyspepsia for many years. It promotes healing of peptic ulcers and reduces their recurrence. The beneficial effect of bismuth on duodenal ulcer disease is thought to be due to an effect on Helicobacter pylori, although it has a rather weak bactericidal effect on H. pylori in vitro. Eradication of H. pylori in duodenal ulcer patients by a combination of bismuth, tetracycline and metronidazole has been reported to increase the density of somatostatin-producing D cells in the antrum. A reduced D cell density in the antral mucosa of duodenal ulcer patients could explain their exaggerated gastrin release. AIMS/METHODS: To test the possibility that bismuth could affect the neuroendocrine cells independently of the presence of H. pylori or not, we gave rats a diluted tripotassium dicitrato bismuthate solution by gastric gavage for 14 days. RESULTS: Tripotassium dicitrato bismuthate treatment did not affect maximal pentagastrin-stimulated acid secretion or histamine release in isolated rat stomachs or the density of argyrophil cells in the oxyntic and antral mucosa. However, it significantly reduced the duodenal concentration of gastrin and calcitonin gene-related peptide, and the density of G cells in the antrum and duodenum. CONCLUSION: The effect of tripotassium dicitrato bismuthate on the G cell may be of significance for its beneficial effect on duodenal ulcer disease.

Administration, Oral↗
PubMed1994

Gastrin regulates histidine decarboxylase activity and mRNA abundance in rat oxyntic mucosa.

Gastrin release histamine from the oxyntic mucosa, stimulates the enzymatic activity of histidine decarboxylase (HDC), increases HDC mRNA abundance, and has a trophic effect on the enterochromaffin-like (ECL) cell. In the present study, we examined the effect of exogenous gastrin on HDC activity and mRNA and the time scale of increase and decline of HDC activity and mRNA. Rats received intravenous infusion of gastrin-(1-17) in different doses or periods of time. Oxyntic mucosal HDC activity and mRNA abundance increased significantly with serum gastrin concentrations in the physiological range. The onset of response was rapid and maximal for both parameters after 2 h. Poststimulatory decrease was maximal 2 h after cessation of gastrin infusion. Those observations suggest that HDC enzymatic activity and mRNA abundance are important in meal-to-meal regulation of gastric secretion. Furthermore, HDC enzymatic activity and mRNA abundance varied in parallel, indicating that HDC mRNA abundance is important in the overall regulation of gastric mucosal HDC activity.

Animals↗
PubMed1993

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↗
PubMed1993

Food stimulation of histidine decarboxylase messenger RNA abundance in rat gastric fundus.

1. Histidine decarboxylase in the enterochromaffin-like cells of the gastric corpus mucosa converts histidine to histamine which in turn stimulates gastric acid secretion. The control of histidine decarboxylase activity is poorly understood. We have examined how fasting and refeeding influence the abundance of the messenger RNA encoding histidine decarboxylase in the gastric corpus of the rat. 2. The polymerase chain reaction was used to generate a probe for detection of histidine decarboxylase messenger RNA in Northern and slot blots of total RNA from the gastric corpus of rats fasted for up to 48 h, or fasted and then refed. A gastrin monoclonal antibody was used to neutralize the action of endogenous gastrin. 3. Fasting progressively reduced histidine decarboxylase messenger RNA abundance by 3- to 4-fold after 48 h. Refeeding induced a rapid increase in histidine decarboxylase messenger RNA abundance which was detectable after 30 min. 4. There was a significant correlation between histidine decarboxylase messenger RNA abundance and plasma gastrin. Administration of gastrin antibody inhibited the increase in histidine decarboxylase activity after 6 h refeeding, but not after refeeding for 30 min. 5. The results suggest that histamine-mediated changes in postprandial acid secretion depend on control of histidine decarboxylase mRNA levels, and that gastrin regulates production of this enzyme in the rat over periods of a few hours.

Animals↗
PubMed1993

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↗
PubMed1993

Control of gastric corpus chromogranin A messenger RNA abundance in the rat.

Enterochromaffin-like cells in the corpus mucosa of the stomach produce histamine in response to gastrin; chromogranin A (CGA) is often used as a morphological marker for these cells, but its functional significance in the gastric mucosa is largely unknown. We have examined whether CGA mRNA abundance in the rat corpus is controlled by endogenous gastrin. In rats fasted for up to 48 h, there was a progressive decline in plasma gastrin and CGA mRNA; refeeding of fasted rats produced a prompt increase in plasma gastrin and an increase in CGA mRNA that was significant after 4 h. Treatment of fasted rats with omeprazole to inhibit acid secretion increased plasma gastrin and CGA mRNA levels. The increased CGA mRNA associated with omeprazole or refeeding was reversed by treatment of rats with the gastrin/cholecystokinin B antagonist CI-988 and gastrin antibody, respectively. The results suggest that CGA production in enterochromaffin-like cells of the rat stomach is part of the functional response of these cells to circulating gastrin.

Animals↗
PubMed1993

Differential control of somatostatin messenger RNA in rat gastric corpus and antrum. Role of acid, food, and capsaicin-sensitive afferent neurons.

Somatostatin messenger RNA in the antrum and corpus of rat stomach was quantified by Northern and slot blotting using a probe generated by the polymerase chain reaction. Fasting for 48 h enhanced the abundance of somatostatin mRNA in the pyloric antral region, but not in the acid-secreting region of the stomach. In fasted rats, somatostatin mRNA in antrum, but not corpus, was decreased by inhibition of acid secretion with omeprazole. In contrast, in rats treated with capsaicin to lesion small diameter afferents there was a significant decrease in somatostatin mRNA abundance in the corpus but not antrum. The effects of capsaicin cannot be attributed to nonspecific changes in gastric endocrine cell gene expression, since the abundance of histidine decarboxylase mRNA (which is a functionally regulated marker for a different gastric endocrine cell type) did not change with capsaicin. Gastric capsaicin-sensitive afferents are rich in calcitonin gene-related peptide, and in rats with antibodies to this peptide there was reduced corpus somatostatin mRNA. Moreover, infusion of calcitonin gene-related peptide in control rats produced a significant increase in somatostatin mRNA in the gastric corpus. The results indicate that somatostatin mRNA abundance is controlled by the gastric luminal contents and the extrinsic afferent innervation, but the relative importance of these factors differs in antrum and corpus: luminal contents are relatively more important in antrum and primary afferents using calcitonin gene-related peptide in the corpus.

Actins↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

Functional control of gastrin releasing peptide (GRP) mRNA in rat stomach.

The gastric factors controlling abundance of mRNA encoding the important neuropeptide, gastrin releasing peptide (GRP) in rat stomach, were examined by Northern and slot blot analysis. Withdrawal of food increased antral GRP mRNA, as did treatment of fed rats with the acid inhibitory drug, omeprazole. There was no change in GRP mRNA abundance in gastric corpus. The data indicate functionally distinct populations of GRP neurons in different regions of the stomach, and control of antral neuropeptide biosynthesis by the gastric luminal contents.

Animals↗
PubMed1992

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↗
PubMed1992

Biologic and immunologic gastrin activity in serum of patients with gastrinoma. Bioassay of gastrin activity in serum.

The biologic gastrin activity in serum from 14 patients with the Zollinger-Ellison syndrome was assessed by the stimulation of histamine release and acid secretion from the isolated vascularly perfused rat stomach and compared with the immunologic activity as determined by radioimmunoassay using an antibody directed towards the active site of the gastrin molecule. Biologic gastrin activity assessed by the stimulation of histamine release was more closely correlated to immunologic gastrin activity than biologic activity assessed by the stimulation of gastrin acid secretion. This study does not contradict the concept that gastrin stimulates acid secretion at least partly by releasing histamine and also shows that the immunologic gastrin activity determined with the help of an antibody directed towards the active site reflects biologic activity.

Aged↗
PubMed1991

Histidine decarboxylase gene expression in rat fundus is regulated by gastrin.

The conversion of histidine to histamine by histidine decarboxylase (HDC) is of central importance in the control of vertebrate acid secretion. We have used PCR-generated probes to study the regulation of HDC gene expression in rat fundic mucosa. When circulating gastrin levels were lowered by fasting or elevated by treatment with omeprazole, there were parallel changes in HDC mRNA abundance. However, when animals with elevated gastrin levels were concurrently treated with the gastrin/CCK-B receptor antagonist PD 134308, HDC mRNA levels were not increased. These data are consistent with the hypothesis that HDC gene expression is regulated by gastrin, over the physiological range of circulating hormone concentrations.

Animals↗