Increase In Serum Gastrin Concentration Research Articles

Serum gastrin concentrations in dogs with primary hyperparathyroidism.

Hypercalcemia has been associated with hypergastrinemia in humans. Hypergastrinemia could be responsible for gastrointestinal (GI) signs in dogs with primary hyperparathyroidism (PHPT). (a) Determine whether hypergastrinemia occurs in dogs with PHPT, (b) assess for potential correlations among ionized calcium (iCa), parathyroid hormone (PTH), and serum gastrin concentrations, and (c) determine whether gastrin concentrations decrease after management of PHPT. Phase 1: 151 client-owned dogs at the time of PHPT diagnosis, Phase 2: 24 dogs that underwent treatment for PHPT. Dogs with azotemia, concurrent disease, or those receiving acid suppressants were excluded. Twenty-four treated dogs had baseline and repeat quantification of serum gastrin, PTH, and iCa concentrations 4 weeks after treatment. The effect of treatment on gastrin, iCa, and PTH concentrations was assessed using Wilcoxon signed rank sum tests. Fisher exact testing was used to compare the proportion of dogs with hypergastrinemia in dogs with and without GI signs. Twenty-seven of 151 PHPT dogs (17.9%) had increased pre-treatment serum gastrin concentrations (median, 45.0 ng/L; interquartile range [IQR], 20.0 ng/L). Gastrin concentrations were not correlated with iCa (P = .92) or PTH (P = .60). Treatment of PHPT decreased PTH (P < .001) and iCa concentrations (P < .001), but not gastrin concentrations (P = .15). The proportion of dogs with hypergastrinemia with and without GI signs did not differ (P = 1.00). Mild increases in serum gastrin concentrations may be seen in dogs with PHPT, but this finding is independent of the presence of GI signs.

Effect of Proton Pump Inhibitors on Colorectal Cancer.

Proton pump inhibitors (PPIs) are administered commonly to aged people; however, their effect on colorectal cancer (CRC) has still not been fully elucidated. Here, we examined the effect of PPIs and consequent alkalization on CRC cells. PPI administration alkalized the fecal pH and increased serum gastrin concentration. PPI and pH8 treatment (alkalization) of CMT93 mouse colon cancer cells inhibited cell growth and invasion, increased oxidative stress and apoptosis, and decreased mitochondrial volume and protein levels of cyclin D1 and phosphorylated extracellular signal-regulated kinase (pERK) 1/2. In contrast, gastrin treatment enhanced growth and invasion, decreased oxidative stress and apoptosis, and increased mitochondrial volume and cyclin D1 and pERK1/2 levels. Concurrent treatment with a PPI, pH8, and gastrin increased aldehyde dehydrogenase activity and also enhanced liver metastasis in the BALB/c strain of mice. PPI administration was associated with Clostridium perfringens enterotoxin (CPE) in CRC lesions. CPE treatment activated yes-associated protein (YAP) signals to enhance proliferation and stemness. The orthotopic colon cancer model of CMT93 cells with long-term PPI administration showed enhanced tumor growth and liver metastasis due to gastrin and YAP activation, as indicated by gastrin receptor knockdown and treatment with a YAP inhibitor. These findings suggest that PPI promotes CRC growth and metastasis by increasing gastrin concentration and YAP activation, resulting in gut flora alteration and fecal alkalization. These findings suggest that PPI use in colorectal cancer patients might create a risk of cancer promotion.

Prevalence of Gastroesophageal Reflux in Cats During Anesthesia and Effect of Omeprazole on Gastric pH.

BackgroundGastroesophageal reflux (GER) is poorly characterized in anesthetized cats, but can cause aspiration pneumonia, esophagitis, and esophageal stricture formation.ObjectiveTo determine whether pre‐anesthetic orally administered omeprazole increases gastric and esophageal pH and increases serum gastrin concentrations in anesthetized cats, and to determine the prevalence of GER using combined multichannel impedance and pH monitoring.AnimalsTwenty‐seven healthy cats undergoing elective dental procedures.MethodsProspective, double‐masked, placebo‐controlled, randomized clinical trial. Cats were randomized to receive 2 PO doses of omeprazole (1.45–2.20 mg/kg) or an empty gelatin capsule placebo 18–24 hours and 4 hours before anesthetic induction. Blood for measurement of serum gastrin concentration was collected during anesthetic induction. An esophageal pH/impedance catheter was utilized to continuously measure esophageal pH and detect GER throughout anesthesia.ResultsMean gastric pH in the cats that received omeprazole was 7.2 ± 0.4 (range, 6.6–7.8) and was significantly higher than the pH in cats that received the placebo 2.8 ± 1.0 (range, 1.3–4.1; P < .001). Omeprazole administration was not associated with a significant increase in serum gastrin concentration (P = .616). Nine of 27 cats (33.3%) had ≥1 episode of GER during anesthesia.Conclusions and Clinical RelevancePre‐anesthetic administration of 2 PO doses of omeprazole at a dosage of 1.45–2.20 mg/kg in cats was associated with a significant increase in gastric and esophageal pH within 24 hours, but was not associated with a significant increase in serum gastrin concentration. Prevalence of reflux events in cats during anesthesia was similar to that of dogs during anesthesia.

The Effect of Marshallagia marshalli on Serum Gastrin Concentrations in Experimentally Infected Lambs.

: Because there appeared to be no data available on serum gastrin concentrations in animals infected with Marshallagia marshalli, and considering the high prevalence of this parasite in livestock throughout many countries, we decided to perform research in the field using experimental infection. After surgical implantation of abomasal cannula into 10 male Baluchi sheep, each animal was orally infected with 5,000 M. marshalli larvae. Serum gastrin concentrations and abomasal pH were measured with a human ELISA kit and a PHM LE438 standard pH electrode, respectively. According to the results obtained from the study, serum gastrin increased after 14 and 21 days post-infection (dpi), while abomasal pH increased after 7 dpi and reached a maximal value 16 dpi. The increase in serum gastrin concentration was revealed 6 days after elevation in abomasal pH, which could be the result of reduced acid secretion. Generally, the present study pointed out that a limited number of M. marshalli could increase serum gastrin concentrations.

Case of primary hepatic gastrinoma: Diagnostic usefulness of the selective arterial calcium injection test.

Gastrinomas mainly occur in the duodenum and pancreas. Primary hepatic gastrinoma is rare and difficult to diagnose because the liver is a frequent site of metastatic gastrinomas. Clinical factors were assessed in a 28-year-old man with diarrhea and heartburn who was hospitalized for recurrent duodenal ulcers. Abdominal ultrasound, endoscopic ultrasound and computed tomography (CT) could not detect a tumor in the duodenum or pancreas. His gastrin level was 846 pg/mL and magnetic resonance imaging showed a mass 12 mm in diameter in the right robe of the liver. A selective intra-arterial calcium injection (SACI) test and 68-gallium edotreotide positron emission tomography CT (Ga-DOTATOC PET-CT) were therefore performed. Calcium gluconate injection into the proper hepatic artery resulted in a marked increase in serum gastrin concentration in the right hepatic vein, with Ga-DOTATOC PET-CT showing uptake only by the liver mass. Following a diagnosis of primary hepatic gastrinoma, the tumor was resected. A histopathological examination indicated gastrinoma. Six months postoperatively, he has no symptoms, is not taking proton-pump inhibitors and his gastrin level remains within the normal range. The SACI test and the clinical course of this patient strongly suggest that the tumor was a primary hepatic gastrinoma. The SACI test is helpful in the diagnosis of primary hepatic gastrinoma.

Serum concentrations of gastrin after famotidine and omeprazole administration to dogs.

BackgroundThe duration of antacid‐induced hypergastrinemia after cessation of administration of omeprazole and famotidine apparently has not been determined in dogs.HypothesisThat serum gastrin will return to basal concentrations by 7 days after cessation of famotidine or omeprazole administration.AnimalsNine healthy, adult, male, research colony dogs.MethodsRandomized, cross‐over design. Serum gastrin was determined daily for 7 days to establish baseline concentrations. Famotidine (1.0 mg/kg q24h) or omeprazole (1.0 mg/kg q24h) was administered PO for 7 days followed by a 14‐day washout. Serum concentrations of gastrin were determined daily during 7 days of administration and daily for 7 days after cessation of administration. Each drug was evaluated in 8 of the 9 dogs.ResultsOmeprazole caused a significant increase in serum gastrin concentration (37.2 ± 7.3 to 71.3 ± 19.0 ng/L; P = .006). Famotidine induced a transient increase in serum gastrin (37.2 ± 7.3 to 65.5 ± 38.5 ng/L; P = .02) that peaked at administration day 3 and declined thereafter. By day 7 after cessation of both drugs, there was no difference in serum gastrin concentrations compared to those before administration (famotidine P = .99; omeprazole P = .99). During or after administration, gastrin concentrations above 3 times the upper reference range were rare (12 of 224 samples).Conclusions and Clinical ImportanceA 7‐day withdrawal from short‐term administration of famotidine or omeprazole is sufficient for serum gastrin to return to baseline concentrations. Withholding famotidine or omeprazole for longer before investigating pathologic causes of hypergastrinemia is unnecessary.

Normal Dogs Treated with Famotidine for 14 days Have Only Transient Increases in Serum Gastrin Concentrations

In people, serum gastrin concentrations increase in response to administration of H(2) receptor antagonists, but the effect of famotidine administration on serum gastrin concentrations has not been evaluated in dogs. To determine if serum gastrin concentrations increase in response to 14 days of famotidine treatment and the time needed to return to baseline after discontinuation of famotidine; define stability of gastrin in samples held at room temperature. Eleven healthy dogs were included in part A (famotidine treatment) and 7 healthy dogs in Part B (serum gastrin stability). In part A, famotidine (0.5 mg/kg p.o. q12h) was administered for 14 days. Fasting blood samples were collected on days 0, 3, 7, 11, 14, 16, 18, 20, and 22. In part B, blood was collected after a 12-hour fast. Gastrin concentrations in serum samples held at room temperature for ≤30 minutes after sampling were compared to concentrations in samples held at room temperature for 150 minutes after sampling. Serum gastrin concentrations increased by day 3 of famotidine administration and returned to baseline concentrations in all dogs by day 14 despite continued famotidine administration. Serum gastrin concentrations were lower (20% mean decrease; P = .0005) in samples held at room temperature for 150 minutes. After 14 days of famotidine administration, clinically healthy dogs have normal serum gastrin concentrations. In a dog with clinical features consistent with gastrinoma, chronic famotidine administration is unlikely to contribute to increases in serum gastrin concentrations.

Clinical significance of serum gastrin levels in patients with colorectal cancer

An association between elevated serum gastrin levels and the presence of human colorectal cancer has been reported, and gastrin has been shown to stimulate the growth of experimentally induced colon neoplasia. The aim of this study was to determine the preoperative and postoperative concentrations of serum gastrin in 53 patients with colorectal cancer and to assess the correlation between gastrin levels and tumor characteristics and prognosis. A prospective study was performed over a six-year period during which 53 patients received potentially curative surgery for colorectal cancer. The prognostic variables used for the analysis included age, sex, tumor site, stage and degree of differentiation, preoperative and postoperative serum values of carcinoembryonic antigen (CEA) and gastrin, cancer-related mortality, and survival. CEA and gastrin serum values were determined using radioimmunological methods. Follow-up was carried out with clinical and radiological tests. The mean preoperative gastrin concentration was 51.2+/-27.4 pg/mL (range 12-146). Significantly increased serum gastrin concentrations, which returned to normal after surgery, were detected only in patients with well-differentiated cancer (74.2+/-28.3 pg/mL; moderately differentiated, 52.1+/-23.8; poorly differentiated, 29.9+/-12.3, p=0.02). The prognosis was unrelated to serum gastrin level; instead, tumor stage, preoperative CEA value, and degree of differentiation affected patient survival. This study showed that the serum gastrin concentration is not an appropriate clinical oncogenic factor. Although occurring only in well-differentiated tumors, serum gastrin is unrelated to the prognosis of patients with colorectal cancer.

Clinical significance of serum gastrin levels in patients with colorectal cancer.

An association between elevated serum gastrin levels and the presence of human colorectal cancer has been reported, and gastrin has been shown to stimulate the growth of experimentally induced colon neoplasia. The aim of this study was to determine the preoperative and postoperative concentrations of serum gastrin in 53 patients with colorectal cancer and to assess the correlation between gastrin levels and tumor characteristics and prognosis. A prospective study was performed over a six-year period during which 53 patients received potentially curative surgery for colorectal cancer. The prognostic variables used for the analysis included age, sex, tumor site, stage and degree of differentiation, preoperative and postoperative serum values of carcinoembryonic antigen (CEA) and gastrin, cancer-related mortality, and survival. CEA and gastrin serum values were determined using radioimmunological methods. Follow-up was carried out with clinical and radiological tests. The mean preoperative gastrin concentration was 51.2+/-27.4 pg/mL (range 12-146). Significantly increased serum gastrin concentrations, which returned to normal after surgery, were detected only in patients with well-differentiated cancer (74.2+/-28.3 pg/mL; moderately differentiated, 52.1+/-23.8; poorly differentiated, 29.9+/-12.3, p=0.02). The prognosis was unrelated to serum gastrin level; instead, tumor stage, preoperative CEA value, and degree of differentiation affected patient survival. This study showed that the serum gastrin concentration is not an appropriate clinical oncogenic factor. Although occurring only in well-differentiated tumors, serum gastrin is unrelated to the prognosis of patients with colorectal cancer.

Effect of rabeprazole on histamine synthesis in enterochromaffin-like cells of mast cell-deficient (Ws/Ws) rats

The effect of rabeprazole, the latest proton pump inhibitor, on the serum gastrin concentration, histidine decarboxylase activity and histamine content of the oxyntic mucosa in Wistar rats, mast cell-deficient (Ws/Ws) rats, and their normal type, +/+, rats was investigated. In Wistar rats, 2 weeks of treatment with rabeprazole (30 mg/kg/day, s.c.) induced a 1.8-fold increase in serum gastrin concentration and a 3.9-fold increase in histidine decarboxylase activity of the oxyntic mucosa over the control levels, whereas neither 2- nor 4-week treatment affected the histamine content of the oxyntic mucosa. In Ws/Ws and +/+ rats, the serum gastrin concentration, histidine decarboxylase activity and even histamine content of the oxyntic mucosa were increased significantly as compared with control levels after the 4-week treatment with rabeprazole. Immunohistochemistry using a histamine antibody confirmed the increase in the histamine content of the oxyntic mucosa after the 4-week treatment with rabeprazole. The finding that there were no differences in serum gastrin concentration and histidine decarboxylase activity between Ws/Ws and +/+ rats, both with and without the 4-week treatment, indicates that mast cells do not respond to endogenous hypergastrinemia elicited by acid-inhibitory treatment. Moreover, the present study clarified for the first time that enterochromaffin-like (ECL) cells in Ws/Ws rats synthesize and store histamine in response to gastrin.

Role of Circulating Gastrin in Colorectal Adenomas and Carcinomas

Background/Aims: A trophic role of gastrin has been convincingly demonstrated in the oxyntic mucosa of the stomach, but is still a matter of debate in the lower gastrointestinal tract. Methods: In order to examine the role of circulating gastrin in colorectal adenoma and carcinoma fasting serum gastrin concentrations were determined in 351 patients undergoing complete colonoscopy. Results: In comparison to controls (n = 145) more patients with either polyps (n = 125) or colorectal carcinoma (n = 81) have slightly increased serum gastrin concentrations, leading to an increased mean, but no change in median serum gastrin levels. In 3 patients preoperatively increased serum gastrin concentrations were normalized after surgical removal of the polyp and/or tumor, suggesting a local release of gastrin from the polyp/tumor. Gastrin concentrations do not correlate with the histopathological classification or malignant potential of adenomatous polyps. Conclusion: In view of these findings a significant role of circulating endogenous gastrin in human colorectal carcinogenesis seems to be unlikely.

Relationship of CagA to serum gastrin concentrations and antral G, D cell densities in Helicobacter pylori infection.

The purpose of this study was to investigate whether the densities of antral gastrin and somatostatin-immunoreactive cells in Helicobacter pylori (H. pylori) infection were related to the bacterial expression of cytotoxin-associated gene A (CagA). 32 patients who had underwent diagnostic esophagogastroduodenoscopy were studied. On the histologic examination all patients had antral gastritis. We divided the subjects into three groups. Group I consisted of 6 patients who had chronic superficial gastritis, group II, 9 patients who had H. pylori-associated gastritis but with no expression of CagA, and group III, 17 patients who had H. pylori-associated gastritis with the expression of CagA. In group I and II, serum gastrin levels, and antral G cell and D-cell were measured. In group III, serum gastrin levels, and antral G cell and D-cell were measured, before and after the eradication of H. pylori. The results were as follows. Firstly, serum gastrin concentrations were significantly higher in the patients with H. pylori infection than in the negative controls. Nextly, there was no correlation between the changes in antral G or D-cell density and H. pylori infection. Thirdly, group III had a significant increase in serum gastrin concentrations and a significant decrease in antral D-cell density than group I. Forthly, eradication of H. pylori in group III showed a significantly increased antral D-cell density. Our results suggest that hypergastrinemia in H. pylori-associated gastritis is relevant to the presence of CagA, and the possible mechanism of hypergastrinemia may be related to antral D-cell deficiency, which is caused by H. pylori infection with the expression of CagA.

Basic aspects of selectivity of pantoprazole and its pharmacological actions.

Pantoprazole sodium is a substituted benzimidazole derivative which controls acid secretion by inhibition of gastric H(+)/K(+)-ATPase. The prodrug pantoprazole accumulates in the acidic space of the parietal cell where it is converted to the pharmacologically active principle, a thiophilic cyclic sulfenamide. The pH-dependent activation profile, i.e., activation at pH 1 versus activation at pH 4-6, is more favorable for pantoprazole than for the other proton pump inhibitors (PPIs) currently available. In vitro, pantoprazole interferes less potently than omeprazole with biological targets not related to gastric acid secretion. The gastric target sites for the pantoprazole sulfenamide are the cysteines 813 and 822 of the catalytic subunit of the H(+)/K(+)-ATPase. In contrast to omeprazole, the two binding sites are located right at the proton channel. In rats, dogs and humans, pantoprazole produces marked and prolonged inhibition of both basal and stimulated acid secretion. Overall, its antisecretory potency is equal to that of omeprazole. Antiulcer activity has been demonstrated for pantoprazole in two rat models. As seen with H(2)-receptor antagonists and other PPIs, pantoprazole causes an increase in serum gastrin concentration which reflects the degree of gastric acid inhibition. Pantoprazole is mainly metabolized by CYP3A4 and 2C19, but displays a lower affinity for these phase I cytochrome P450 enzymes than omeprazole. In contrast to the latter, pantoprazole is further conjugated with sulfate by the hepatic phase II metabolism. These two differences may explain why pantoprazole does not interfere with the metabolism of any other drug thus far tested in humans.

Persistently increased gastrin and decreased pepsinogen concentrations in serum from some patients with Graves' disease of triiodothyronine-predominant type and common type.

This study aimed to investigate the cause of persistently increased serum gastrin concentration seen in some Graves' disease patients even when euthyroid during antithyroid drug treatment. The subjects studied consisted of three groups: 33 patients with a common-type of Graves' disease, 14 with triiodothyronine (T3)-predominant Graves' disease (characterized from previous studies as having potent immunologic abnormalities including greater concentrations of thyroid-stimulating antibodies together with larger goiter size), and a group of 20 normal subjects. Fasting serum gastrin concentrations in common Graves' disease patients were significantly higher than those of normal subjects (58.4 +/- 38.9 pmol/L vs. 37.8 +/- 18.9 pmol/L [mean +/- SD], p < 0.05). The serum gastrin concentrations were even greater in T3-predominant Graves' disease patients than common Graves' disease patients (162.9 +/- 224.0 pmol/L vs. 58.4 +/- 38.9 pmol/L, p < .05). Serum pepsinogen I (PGI) concentrations were significantly lower in the T3-predominant patient group than the common Graves' group (24.0 +/- 12.9 ng/mL vs. 39.7 +/- 19.6 ng/mL, p < .05). Serum ratios of PG I to PG II were significantly lower in the T3-predominant Graves' disease patients than normal subjects (3.59 +/- 2.66 vs. 5.97 +/- 1.56, p < .01). The ratios also had a significant (p < .05) inverse correlation with serum gastrin concentrations in T3-predominant Graves' disease patients. The results suggest that autoimmune gastritis is associated with Graves' disease, particularly in patients with potent thyroid-autoimmunity.

Time-Dependent Changes of Serum Gastrin and Gastrin Receptors in the Rat Oxyntic Mucosa after Proximal Gastric Vagotomy

Proximal gastric vagotomy (PGV) is a first-choice approach for the surgical treatment of duodenal peptic ulcer. However, a high percentage of recidivism takes place after this surgical strategy. To study the possible involvement of gastrin in ulcer recidivism, serum gastrin levels and gastrin receptors in gastric mucosa were determined at several times after PGV in rats. Gastrin concentration was determined using a commercial radioimmunoassay kit and gastrin receptors were analyzed in oxyntic mucosa membrane preparations using125I-labeled 15-Leu–gastrin-17 as label. Our results show a significant, time-dependent increase in serum gastrin concentration, reaching highest values at 12 weeks after PGV. Similarly, a significant increase in the number of gastrin receptors (Bmax) and in the dissociation constant (Kd) occurred from 1 to 12 weeks post-PGV. Since gastrin exerts a positive feedback effect on its receptors, the PGV-dependent increase in serum gastrin concentration explains the up-regulation of the gastrin receptors in the rat oxyntic mucosa. Furthermore, an increase in the number of gastrin receptors after vagotomy may be at least partially responsible for the recidivism in duodenal peptic ulcers after this surgical approach.

Parenterally or enterally administered anti-somatostatin antibody induces increased gastrin in suckling rats.

This study demonstrates the effectiveness of parenteral and oral anti-somatostatin monoclonal antibody to stimulate gastrin cell activity in suckling rats. Intraperitoneal anti-somatostatin monoclonal antibody increased serum gastrin concentration (> 2-fold), and orally administered antibodies retained their neutralizing capabilities as demonstrated by a 30% induction of gastrin synthesis. Absorption of luminal monoclonal antibody was time dependent and saturable as demonstrated by measurement of serum murine immunoglobulin G and the subsequent effects on serum gastrin and antral gastrin mRNA concentrations. Enhanced gastrin synthesis after oral administration required whole antibody in that enterally delivered F(ab')2 fragments were not absorbed and did not increase serum gastrin concentrations. In addition, pretreatment with excess Fc fragments decreased monoclonal antibody absorption and eliminated the serum gastrin response to oral monoclonal antibody. These results demonstrate that orally administered murine anti-somatostatin monoclonal antibody was rapidly and efficiently absorbed via an Fc-dependent mechanism and retained immunoneutralizing activity against endogenous somatostatin, neutralizing its inhibition of gastrin cell activity. These results indicate that orally administered monoclonal antibodies could potentially be used to determine the role of other peptides and growth factors as potential physiological regulators during the suckling period of postnatal development.

In vivo mitogenic effects of estradiol on colon cancers: Role of gastrin and gastrin receptors

We have previously reported mitogenic effects of gastrin on a mouse colon cancer (MC-26) cell line in vivo. The present studies were undertaken to determine if gonadal hormones can influence the mitogenic response of MC-26 cells to gastrin. The female gonadal hormone, estradiol (E 2), was determined to be as mitogenic as pentagastrin (PG) for the growth of MC-26 tumors in mice; the mitogenic effects of E 2 and PG were not additive. Female gonadal hormones were furthermore as effective as PG in maximally up-regulating gastrin receptor (GR) concentrations on MC-26 tumor membranes, which was confirmed in autoradiographic studies. Since PG and E 2 had similar and non-additive trophic effects it was hypothesized that gastrin may be mediating the trophic effects of E 2. Serum gastrin concentrations were significantly increased in E 2 treated ovariectomized mice that correlated with an increase in tumor weights; E 2 however was ineffective in stimulating the release of gastrin from perfused rat stomachs indicating that the increase in serum gastrin concentration on long-term treatment with E 2 was mediated by some other mechanism. Saturable high-affinity E 2 binding sites were not measured in MC-26 cells and tumors, supporting the possibility that mitogenic effects of E 2 were probably mediated via indirect mechanisms. In summary our results indicate that both E 2 and PG are equally mitogenic for colon cancer cells in vivo which may explain the sex- and age-related discrepancy in the incidence of human colon cancers.

Ultrastructural investigations of the enterochromaffin-like (ECL) cells in three different rat strains (Sprague-Dawley, Fischer 344, Wistar) after treatment with the H+,K(+)-ATPase inhibitor pantoprazole.

The purpose of the present study was the evaluation of ultrastructural characteristics of the enterochromaffin-like (ECL) cells in the fundic mucosa of three different rat strains without treatment and after treatment with the H+, K(+)-ATPase inhibitor pantoprazole. In the study, 20 one year old female Sprague Dawley (SD), Fischer 344 (F) and Wistar (W) rats each were treated orally for three months with 4 mg pantoprazole/kg/d or with the vehicle only. The control animals showed close conformity of ECL cell density and morphology in all three strains. Treatment with pantoprazole led to a significant increase in serum gastrin concentration and GPC density in all strains. However, the electron microscopically determined ECL cell density was markedly increased in the SD strain only. Ultrastructurally all treated rats showed activation of the ECL cells, and enhanced histamine release. The SD and F strains had an enhanced proportion of large ECL cell granules, with the F rats also showing an increased granule density. In contrast, the treated W rats were found to have a lower granule density and a higher proportion of small and medium sized granules compared to their controls.

Response of the antral mucosa of the rat stomach to 2,3,7,8-tetrachlorodibenzo- p-dioxin

2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD) produces a striking hypergastrinemia in rats that is thought to mediate the antiatrophy effect of TCDD on the oxyntic gland mucosa of the stomach. However, effects of TCDD on the antral mucosa, which is the origin of most physiologically released gastrin and is not a target for the trophic action of gastrin, has yet to be thoroughly investigated. Also gastrin release from gastrin-containing cells (i.e., G-cells) in the antral mucosa is inhibited by the paracrine secretion of somatostatin from D-cells in the antrum. Our purpose was to determine if the antral mucosa is affected by the trophic influence of TCDD and if alterations in antral mucosa levels of gastrin or somatostatin cause the hyper-gastrinemia. TCDD (100 μg/kg, Day 14 post-treatment) had a trophic effect on the antral mucosa. This was demonstrated histologically and by significant increases in antral wet weight and antral mucosa height. In contrast, pair-fed control rats that lost the same amount of body weight developed antral mucosa atrophy. With respect to serum and antral levels of gastrointestinal hormones, TCDD produced a 7- to 10-fold increase in serum gastrin concentrations that was not detected until Day 14 post-treatment. In contrast, serum gastrin concentrations in pair-fed control rats were comparable to those of control rats. The number of G-cells in the antral mucosa was not affected by either TCDD treatment or paired-feed restriction. These findings demonstrate that hypergastrinemia in TCDD-treated rats is not caused by reduced feed intake or antral G-cell hyperplasia. A major finding was that antral mucosa levels of both gastrin and somatostatin were decreased significantly in TCDD-treated rats. However, the temporal development and dose-decreased of these TCDD effects on antral hormone levels were quite different than those for hypergastrinemia. TCDD-induced decreases in antral levels of gastrin and somatostatin were detected 1 week earlier than hypergastrinemia. Also, the ED50 of TCDD on Day 14 post-treatment for the decrease in antral mucosa content and concentration of gastrin (29 and 22 μg/kg, respectively) and somatostatin (24 and 19 μg/kg, respectively) was less than that for hypergastrinemia (46 μg/kg). These time- and dose-dependent differences demonstrate that hypergastrinemia in TCDD-treated rats is not a consequence of reduced antral levels of gastrin or somatostatin. We conclude that the antral mucosa, an epithelial tissue not responsive to the proliferative effect of gastrin, is nevertheless a target for the trophic influence and gastrointestinal hormone-altering effects of TCDD.

Effect of truncal vagotomy on parietal cell mass and antral gastrin cell mass in dogs

Vagotomy is known to reduce acid secretion and to increase serum gastrin concentrations. However, there is minimal information on the effect of vagotomy on parietal cell mass or gastrin cell mass. Basal and maximal acid secretions and fasting serum gastrin concentrations were measured in 22 gastric fistula dogs with pyloromyotomy before and up to 56 days following complete bilateral truncal vagotomy (n = 11) or sham vagotomy (n = 11). Dogs underwent total gastrectomy on postoperative day 9 (n = 5 per group) or day 56 (n = 6 per group). Parietal cells were stained with Luxol fast blue and parietal cell mass determined with computer-assisted histomorphometry. Parietal cell mass averaged 10.68 ± 0.90 billion in control dogs and correlated significantly with maximal acid output (r = 0.76; P < 0.01). Vagotomy reduced maximal acid output by 40%–50% (P < 0.001) but had no significant effect on parietal cell mass (8.99 ± 1.00 billion). Vagotomy increased serum gastrin concentrations significantly, but antral gastrin cell mass in vagotomized dogs (5.66 ± 1.00 million) was not significantly different than that in control dogs (4.74 ± 0.50 million). Thus, vagotomy did not lead to parietal cell hypoplasia or gastrin cell hyperplasia despite profound alterations in parietal cell and gastrin cell function.