The relevance of luminal release is doubtful.
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Animals↗
Biomedical subjects
A K Sandvik
Publications and source records attributed to A K Sandvik.
Neuroendocrine cells in the prostate of the rat, guinea pig, cat, and dog.
BACKGROUND: The neuroendocrine (NE) cells in the human prostate gland probably have a local regulatory role in both prostatic growth and differentiation as well as in the exocrine secretory process. Moreover, NE cells may be involved in the pathogenesis of both prostatic cancer and hyperplasia. To enhance the knowledge of the physiological and pathophysiological role of NE cells in the prostate gland, we wanted to establish an experimental animal model. METHODS: All lobes of the prostatic complex of rats with different serum levels of testosterone, as well as the prostate of the guinea pig, cat, and dog, were studied. Prostatic tissue fixed in different fixatives was studied with regard to NE cells by using cytochemical and immunohistochemical staining techniques, as well as Northern blotting and reverse transcriptase polymerase chain reaction (RT-PCR) for detection of rat chromogranin A (CgA) mRNA. RESULTS: The present study indicates the absence of NE cells in the rat prostatic complex. No expression of CgA RNA was detectable either by Northern blotting or by RT-PCR. Only a few argyrophil cells in the prostatic complex of guinea pig were detected in tissue fixed in Bouin's solution. CONCLUSIONS: Rat, guinea pig, cat, and dog are not suitable animals in physiological studies of NE cells in the prostate gland.
Animals↗
Regulated expression of GATA-6 transcription factor in gastric endocrine cells.
BACKGROUND & AIMS: GATA transcription factors may regulate gene expression in developing tissues, including gut epithelium. In the stomach, their expression has been linked to regulation of proton pump genes. However, GATA consensus sequences also occur in the promoter of the histidine decarboxylase gene, located in enterochrommafin-like cells. The aim of this study was to determine if GATA factors are located in gastric endocrine cells and to examine their expression during development and in response to changes in the gastric luminal environment. METHODS: Polymerase chain reaction cloning, Northern blot, and gel shift assays were used to examine GATA expression in gastric endocrine cells; changes in GATA messenger RNA during development and in response to fasting, feeding, and gastric achlorhydria were determined by Northern blot. RESULTS: GATA-6 was expressed strongly in rodent gastric endocrine cell fractions, in a human ECL cell tumor, and in an endocrine cell line (STC-1) derived from gut epithelium; proteins from STC-1 cells bound specifically to GATA consensus sequences in the human histidine decarboxylase promoter. GATA messenger RNA abundance was up-regulated during terminal differentiation of the rat stomach and on feeding after a fast. CONCLUSIONS: The GATA-6 transcription factor is expressed in gastric endocrine cells and is a potential regulator of gastric differentiation and of genes involved in the response to feeding.
Achlorhydria↗
Review article: the pharmacological inhibition of gastric acid secretion--tolerance and rebound.
During the last decade our understanding of the regulation of gastric acid secretion has changed considerably. The recognition that gastrin acts mainly by releasing histamine from the enterochromaffin-like (ECL) cell is of major importance. It is now necessary to review and seek new explanations for the development of tolerance and for the post-treatment acid hypersecretion that may be observed when treatment with acid-secretory inhibitors is discontinued. Tolerance and rebound related to H2-receptor antagonists has previously been explained as upregulation of gastrin and/or histamine H2-receptors, and/or an increased parietal cell mass. Experimental evidence for these theories is scarce. On the other hand, tolerance can now be explained by a gastrin-induced increase in ECL cell-derived histamine at the parietal cell H2-receptor competing with the antagonist. The lack of tolerance to proton pump inhibitors may be explained by their mode of action, being non-competitive and acting at the H+, K+-ATPase rather than at stimulatory receptors. Post-treatment rebound acid hypersecretion can be understood as gastrin upregulating and/or stimulating growth of the ECL cell, leading to increased amounts of releasable histamine post-treatment. Novel experimental data strongly support this view of the development of tolerance and post-treatment rebound acid hypersecretion.
Animals↗
Melatonin in mast cells and tumor radiosensitivity.
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Animals↗
The diffuse neuroendocrine system and extrapineal melatonin.
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Animals↗
Gastrin stimulates histamine release from the isolated pig stomach.
BACKGROUND: Gastrin has been shown to give an immediate and dose-dependent histamine release preceding acid secretion in the totally isolated, vascularly perfused rat stomach. METHODS: In the present study we prepared isolated, vascularly perfused stomachs taken from pigs and examined the effect of pentagastrin in a concentration of 520 pM on the histamine release to the vascular bed. Pentagastrin was given for three 5-min periods at 10-min intervals, and histamine was determined by a radioimmunoassay method. RESULTS: Each pentagastrin dose resulted in stimulation of histamine release in the three pig stomachs examined. The various histamine concentrations increased to levels previously shown to stimulate aminopyrine accumulation in isolated pig parietal cells. CONCLUSION: The present study shows for the first time that gastrin induces histamine release to the vascular bed in the pig, as previously shown for the rat and dog.
Animals↗
Bombesin inhibits histamine release from the rat oxyntic mucosa by a somatostatin-dependent mechanism.
BACKGROUND AND METHODS: This study examines the effect of bombesin on endogenous somatostatin and the histamine-synthesizing enterochromaffin-like cells. Somatostatin and histamine were measured in the venous effluent of isolated/antrectomized vascularly perfused rat stomachs after administration of bombesin and gastrin alone or combined. Histidine decarboxylase (HDC) enzyme activity and mRNA abundance were measured in the gastric corpus after intravenous administration of bombesin to conscious rats. RESULTS: Bombesin released somatostatin from the isolated stomachs and reduced basal and gastrin-stimulated venous histamine. Somatostatin antiserum partially reversed the effect of bombesin on basal and gastrin-stimulated histamine release. In conscious fed rats, intravenous bombesin doubled serum gastrin concentrations and increased HDC activity. CONCLUSION: We conclude that endogenous (paracrine) somatostatin inhibits basal and gastrin-stimulated histamine release from the ECL cell. In intact animals this effect is surmountable by simultaneously released gastrin, suggesting that a balance between the effects of gastrin and somatostatin determines the activation of the ECL cell.
Animals↗
Evaluation of biologic gastrin activity of compound CI-988 in the isolated, vascularly perfused rat stomach.
BACKGROUND: The peptoid CI-988 has previously been shown to have high affinity for the cholecystokinin (CCK)-B/gastrin receptor and has been reported to be a powerful CCK antagonist in many systems, although it has agonist activity on histidine decarboxylase in the rat. METHODS: In the present study the effect of CI-988 on acid secretion and histamine release in the totally isolated, vascularly perfused rat stomach was assessed. RESULTS: CI-988 was found to be a gastrin agonist with regard to the stimulation of both histamine release and acid secretion. CONCLUSION: Thus, in this stomach model CI-988 behaved as a CCKB/gastrin agonist. The present study underlines the importance of testing the biologic activity of ligands in models with sufficient sensitivity.
Animals↗
The fade of gastrin-stimulated gastric acid secretion in the rat is due to depletion of releasable mucosal histamine.
The present study examines the applicability of the isolated, acid-secreting vascularly perfused rat stomach for long-term physiological and pharmacological studies. The model was used to study the fade of acid secretion during gastrin stimulation. The stomachs were stimulated by exogenous gastrin or histamine alone or in succession. Acid secretion and venous histamine concentrations were measured. Gastrin and histamine potently stimulated acid output, histamine-stimulated acid secretion was sustained for 300 min while gastrin-stimulated secretion peaked at 120 min and declined towards basal output at 300 min. Stomachs rendered tachyphylactic to gastrin could be re-stimulated by exogenous histamine. Venous histamine output during gastrin stimulation decreased in parallel to acid secretion. This, the acid-secreting, isolated vascularly perfused rat stomach can be used for physiological and pharmacological studies with histamine as stimulant for at least 300 min. The present results strongly indicate that the effect of gastrin on acid secretion is mediated by histamine, and that fade of acid secretion during stimulation with gastrin is due to depletion of releasable mucosal histamine.
Animals↗
The gastrin-histamine sequence.
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Animals↗
The peroxisome-proliferator ciprofibrate induces hypergastrinemia without raising gastric pH.
The ECL-cell hyperplasia and ECL-cell carcinoids occurring during long-term treatment with ciprofibrate, have been attributed to hypergastrinemia secondary to an inhibitory effect on acid secretion. However, nobody has given any explanation of the mechanism by which ciprofibrate and related phenoxyisobutyrate derivates inhibit acid secretion. Moreover, the reported inhibition of acid secretion has only been moderate, in contrast to the profound inhibition of acid secretion needed to induce similar ECL-cell changes. To re-examine the effect of ciprofibrate on gastric acidity and serum gastrin, we randomly assigned 33 male Fisher rats into three treatment groups (100 or 20 mg/kg/day of ciprofibrate and control) during a period of 4 weeks. Daily assessments of gastric acidity was done by gastric intubation, using a tube with a diameter of 2.0 mm allowing the introduction of an infant pH-catheter. Measurements were done in all animals 5 days a week. Ciprofibrate did not raise gastric pH. On the contrary, the highest dose increased the acidity. Serum gastrin levels measured in blood taken by vein puncture before the initiation of the drug treatment and on the last day of the 4 week treatment period, revealed a dose-related significant hypergastrinemic effect of ciprofibrate. The slight increase in gastric acidity in the ciprofibrate high-dose group is most likely due to the hypergastrinemia provoked by the drug. This hypergastrinemia is therefore not secondary to an inhibition of acid secretion, but may be due to a direct effect of ciprofibrate on the G-cell. The ECL-cell hyperplasia and the ECL-cell carcinoids, which develop during treatment with peroxysome-proliferators are thus due to hypergastrinemia, which is not secondary to inhibition of acid secretion.
Animals↗
Papillomatosis of the esophagus.
Esophageal papillomas are rare. Both local irritation as by gastroesophageal reflux and infections with human papillomavirus (HPV) have been implicated as etiological factors. We here describe a 28-year-old female patient with massive esophageal papillomatosis. The clinical course has been mild, with signs of regression after a 3 1/2-year observation period. An extensive evaluation showed no predisposing diseases, and test results for HPV using sensitive methods were negative despite histological features suggesting virus infection and concomitant pharyngeal papillomas that are known to be caused by HPV. This case underlines the incomplete understanding of the etiology of this disease.
Adult↗
Marked increase in gastric acid secretory capacity after omeprazole treatment.
BACKGROUND: In contrast with the histamine2 (H2) blockers, proton pump inhibitors have not been shown to give rebound hypersecretion of acid. Taking into consideration the hyperplasia of the enterochromaffin-like (ECL) cell provoked by hypergastrinaemia secondary to profound acid inhibition and the central role of histamine from ECL cells in the regulation of acid secretion, the lack of any rebound acid hypersecretion after treatment with proton pump inhibitors has been questioned. AIMS: To reassess the effect of treatment with omeprazole on post-treatment acid secretion. METHODS AND PATIENTS: Basal and pentagastrin stimulated acid secretion were determined in nine patients with reflux oesophagitis before and 14 days after termination of a 90 day treatment period with the proton pump inhibitor omeprazole (40 mg daily). Basal gastrin release were determined before and during omeprazole treatment. Furthermore, biopsy samples from the oxyntic mucosa were taken before and at the end of the treatment period for chemical (histamine and chromogranin A (CgA)) evaluation of the ECL cell mass. RESULTS: A substantial increase in meal stimulated gastrin release during omeprazole treatment resulted in an increased ECL cell mass. Furthermore, CgA in serum increased during omeprazole treatment suggesting that serum CgA may be used as a test to evaluate ECL cell hyperplasia. A significant increase in basal and a marked (50%) and significant increase in pentagastrin stimulated acid secretion were found after treatment with omeprazole. CONCLUSIONS: Increased acid secretion after a conventional treatment period with a proton pump inhibitor is probably due to ECL cell hyperplasia and may have negative consequences for acid related diseases.
Adult↗
Chromogranin A and pancreastatin-like immunoreactivity in normal pregnancies.
Placenta is a neuroendocrine organ, and we therefore wanted to study the occurrence of the general neuroendocrine marker chromogranin A (CgA) and its split product pancreastatin. CgA and pancreastatin-like immunoreactivity (PST-LI) were determined by ELISA and RIA methods, respectively, in homogenates from term placentas, sera from pregnant women, nonpregnant women, umbilical cords, and in amniotic fluids. In placental homogenates, the mean level of CgA was 7.1 +/- 8.6 pmol/g wet wt (mean +/- SD), whereas PST-LI was not detectable. CgA immunoreactivity was demonstrated by immunofluorescence studies of isolated trophoblasts and decidual cells from term placentas. In trophoblasts, CgA was colocalized with human chorionic gonadotropin (hCG) and human placental lactogen. By Northern blotting, a distinct band corresponding to CgA messenger RNA (mRNA) was demonstrated in the placental cell line, whereas, in placental homogenates, a mRNA band of a slightly larger size was found. Median CgA level in maternal sera at term tended to be higher (median: 469 pmol/L, range 61-980 pmol/L, P < 0.1) than at 6-11 weeks (286 pmol/L, 61-653 pmol/L) or in sera from nonpregnant women (306 pmol/L, 204-469 pmol/L). In umbilical cord sera, median CgA level was significantly higher (898 pmol/L, 102-2245 pmol/L, P < 0.05) than in term sera. Median serum level of PST-LI was significantly higher at term (38 pmol/L, 0-131 pmol/L) than at 6-11 weeks (9 pmol/L (0-85 pmol/L, P < 0.05), than in nonpregnant women (6 pmol/L, 0-52 pmol/L, P < 0.05), and in umbilical cord sera (12 pmol/L, 0-76 pmol/L, P < 0.05). In amniotic fluid, median CgA value was significantly higher at term (1163 pmol/L, 714-1673 pmol/L) than at 14-17 weeks (551 pmol/L, 82-980 pmol/L, P < 0.01), whereas median level of PST-LI was significantly higher at 14-17 weeks (32 pmol/L, 6-97 pmol/L) than at term (0 pmol/L, 0-15 pmol/L, P < 0.01). To our knowledge, this is the first report describing the presence of CgA and PST-LI in placenta and amniotic fluid and the occurrence CgA mRNA in placental tissue and in a placental cell line. The presence of CgA in placenta may indicate a physiological role in pregnancy.
Adolescent↗
[Damages to the large intestine induced by non-steroidal anti-inflammatory agents].
Non-steroidal anti-inflammatory drugs can cause side effects in the large bowel. We describe two cases which illustrate some of the aspects associated with this problem, and briefly outline the different types of side effects encountered, and possible pathogenetic mechanisms. It is emphasized that non-steroidal anti-inflammatory drugs can cause exacerbation of quiescent colitis in patients with inflammatory bowel disease. The use of these drugs in such patients should be very restrictive. Non-steroidal anti-inflammatory drugs can also precipitate de novo colitis. They are also associated with collagenous colitis, non-gangrenous ischemic colitis, complications to diverticular disease, and ulceration of the colon.
Adult↗
Bioassay of gastrin using the isolated vascularly perfused rat stomach. A new, simplified and sensitive method.
Radioimmunoassays are sensitive and specific methods for measurement of the concentrations of regulatory peptides. However, aspects of physiological, pathophysiological and pharmacological research require knowledge about the biological activity which does not necessarily vary concomitantly with immunological activity. The present work describes a simplified bioassay for gastrin based on the gastric histamine releasing properties of this peptide, using an isolated vascularly perfused rat stomach preparation with a crystalline perfusate and a specific radioimmunoassay for histamine. The establishment of a dose-response curve is described, as well as the utilization of the bioassay on sera from patients with hypergastrinaemia. The method is sensitive for gastrin in the low (4 pmol L-1) picomolar range.
Anemia, Pernicious↗
Differential expression and regulation of SSTR2 messenger RNA in rat gastric antrum and corpus.
Somatostatin modulates both endocrine and exocrine functions in the gastric mucosa, where three of the five cloned somatostatin receptors are present. This study examines changes in somatostatin receptor (SSTR) mRNA abundance during fasting, feeding, and profound acid inhibition with omeprazole. Serum gastrin as well as somatostatin and SSTR mRNA abundances were measured in antrum and corpus. In Northern blots of corpus RNA, the SSTR2 probe hybridized with two previously reported species of mRNA (2.4 and 2.8 kb); in addition, a weak previously unreported 1.6-kb band was detected. In antrum, the 1.6-kb band dominated. Fasting increased antral somatostatin mRNA from 100 +/- 8 to 161 +/- 24% and SSTR mRNA from 100 +/- 10 to 179 +/- 14% (P < 0.05). Omeprazole reduced antral somatostatin mRNA to 34 +/- 4% of control (P < 0.05) and elevated SSTR mRNA to 135 +/- 5% of control (P < 0.01). Omeprazole treatment reduced corpus somatostatin mRNA to 59 +/- 5% (P < 0.05), and elevated SSTR mRNA to 140 +/- 3% of control (P < 0.01). The results therefore indicate that a novel SSTR mRNA subtype exists in the stomach and predominates in the antrum. The abundance of this SSTR mRNA is upregulated by both fasting and achlorhydria; conditions that increase or decrease endogenous antral somatostatin, respectively.
Animals↗