Increase In Acid Output Research Articles

Sham Feeding Induced Gastric Acid Secretion in Patients with Caustic Induced Esophageal Stricture.

Caustic ingestion can lead to structural changes in the upper gastro-intestinal tract. However, there is limited data on the effect of caustic ingestion on gastric secretion. This study was planned to determine changes in gastric acid output after sham feeding in patients with caustic induced esophageal stricture and to compare it with healthy controls. It was a prospective study done at tertiary care center in North India. Consecutive patients with caustic induced esophageal stricture were evaluated for the study. Gastric secretory function was estimated in the basal state and after modified sham feeding. These results were compared withage-matched controls. The mean age of the included patients (n = 18) was 30.11 ± 9.19years and 13 patients were male. 16 (88%) patients had history of acid ingestion. Patients with caustic sequelae had significantly lower basal and stimulated acid secretion compared to controls (n = 10) (5.84 ± 2.44mmol/hr; p < 0.01 and 17.16 ± 7.53mmol/hr; p < 0.01; respectively). Patients with lower esophageal stricture (n = 8) had significantly lower increase in acid output compared to patients with stricture elsewhere in esophagus (0.20 ± 0.3 vs. 2.31 ± 1.74mmol/hr, p < 0.01). Patients with lower esophageal involvement had significantly lower stimulated acid secretion and increase in acid secretion compared to controls (4.74 ± 4.67 vs. 17.16 ± 7.53mmol/hr; p < 0.01 and 20 ± 0.3 vs. 2.09 ± 0.88mmol/hr; p < 0.01; respectively).

Influence of the Novel Histamine H3 Receptor Antagonist/Inverse Agonist M39 on Gastroprotection and PGE2 Production Induced by (R)-Alpha-Methylhistamine in C57BL/6 Mice.

The role of histamine H3 receptors (H3Rs) in the regulation of gastroprotection and production of prostaglandin E2 (PGE2) as well as somatostatin remains contradictory. Therefore, the effects of the H3R antagonist/inverse agonist M39 on in vivo acidified ethanol-induced gastric ulcers and gastric acid secretion in the C57BL/6 mice were assessed. Results showed that acute systemic administration of H3R agonist (R)-α-methylhistamine (RAMH, 100 mg/kg, i.g.) significantly reduced the severity of ulcer index, increased gastric acid output, and increased mucosal PGE2 production without any alteration of somatostatin concentration in gastric juice. However, only acute systemic administration of the H2R agonist dimaprit (DIM, 10 mg/kg, p.o.) significantly decreased the level of somatostatin measured in gastric juice. Moreover, acute systemic administration of M39 (0.3 mg/kg, i.g.) abrogated the RAMH-induced increase of acid output as well as PGE2 production, but not the DIM (10 mg/kg, i.g.)-stimulated acid secretion, indicating that RAMH as well as M39 modulate the gastroprotective effects through interactions with histamine H3Rs. The present findings indicate that agonistic interaction with H3Rs is profoundly involved in the maintenance of gastric mucosal integrity by modulating PGE2 as well as gastric acid secretion, with no apparent role in the regulation of the inhibitory influence of somatostatin.

Levels of proteins and immunoglobulins in rabbit blood during Рassalurosis

The purpose of our work was to determine the influence of Passalurus ambiguus on proteinogram and the level of immunoglobulins in the blood of rabbits. Analog groups of male rabbits of 3–5 months of age were selected for the experiments. Intensity of invasion was determined by the method of the MacMaster. By spectrophotometric method in the blood of animals there was determined: the content of total protein, albumin, globulin fractions, the level of IgA, IgG, IgM — discrete deposition method according to M. Kostina. Rabbits with pasalurosis have different levels of invasion intensity (II): low (II = 276.47 ± 43.33 eggs/g of feces), high (II = 2,446.67 ± 422.11 eggs/g of feces) — II and medium (II = 1,293.75 ± 275.80 eggs/g of feces) — III research groups. We did not find eggs in the control group. The total protein content was significantly (p &lt; 0.001) higher — from 1.38 times to 1.66 times compared with healthy ones, due to an increase in the content of globulins from 2.08 times (p &lt; 0.001) to 2.26 times (p &lt; 0.001), which led to a decrease in the protein ratio from 2.16 times (p &lt; 0.001) to 3.29 times (p &lt; 0.001) in sick animals with different II. We recorded a high content of γ-globulins almost 1.4 times in these animals compared to healthy ones. We observed a high content of β-globulins and α2-globulins by 6.70% and 7.05% (p &lt; 0.01) and 5.15% and 3.99% (p &lt; 0.05) in animals II and III experimental groups in comparison with control group. A decreased level of uric acid from 4.77 times (p &lt; 0.001) to 6.19 times (p &lt; 0.001) in rabbits with passalurosis is probably due to a violation of the process of its formation in the liver against the background of an increase in acid output through the intestines and kidneys. The creatinine level in experimental rabbits was significantly higher in groups I, II, III by 42.64% (p &lt; 0.001), 46.49% (p &lt; 0.001) and 44.42% (p &lt; 0.001), respectively, compared with the control. IgA and IgG levels were high (p &lt; 0.001) in comparison to healthy rabbits: 2.22 and 2.16 times (in animals with low II), 1.51 and 1.85 times (in animals with high II). We observed a significant (p &lt; 0.001) high level of IgM against the control 1.58 times, 1.82 times and 1.70 times, respectively, in groups I, II, III of infected rabbits. The content of total protein, globulins, γ-globulins, IgA, IgG, IgM and creatinine were significantly higher (p &lt; 0.001) in the blood of sick rabbits than healthy ones. We observed significant changes in the proteinogram of rabbits with high levels of II. These changes indicate an increase in the body’s immune defense under the influence of Passalurus ambiguus. We found a decreased level of uric acid and a protein coefficient due to the low percentage of albumin in sick rabbits. This is possibly due to a violation of the process of their formation in the liver against the background of increased output

Anti-inflammatory and carbonic anhydrase restoring actions of yam powder (Dioscorea spp) contribute to the prevention of cysteamine-induced duodenal ulcer in a rat model

Increased acid output, accompanied with a defective defense system, is considered a fundamental pathogenesis of duodenal ulcer (DU). However, relapse of DU occurs despite proton pump inhibitors and H2 receptor antagonists, hence imposing the enforcement of the defense system. Dried powder of the yam tuber (Dioscorea spp) has been used in traditional folk medicine as a nutritional fortification. We hypothesized that dried-yam powder would prevent DU through improvement of anti-inflammatory actions and carbonic anhydrase (CA) activity. Therefore, we investigated the preventive effects of dried-yam powder against the cysteamine-induced DU and elucidated the underlying mechanisms. Duodenal ulcers were induced in Sprague-Dawley rats by intragastric administration of 500 mg/kg cysteamine-HCl. The dried-yam powder was used as a pretreatment before the cysteamine-HCl. The number and size of DU were measured. The expressions of inflammation mediators were checked in duodenal tissues, and the expressions of CAs and malondialdehyde levels were also examined. Cysteamine provoked perforated DU, whereas dried-yam powder significantly prevented DU as much as pantoprazole and significantly reduced the incidence of perforation. The messenger RNA expressions of cyclooxygenase-2 and inducible nitric oxide synthase were remarkably decreased in the yam group compared with the cysteamine group, and the serum levels of proinflammatory cytokines including interleukin-1β, interleukin-6, and tumor necrosis factor were significantly attenuated in the yam group. Cysteamine significantly decreased the expression of CAs, whereas yam treatment significantly preserved the expressions of CA IX, XII, and XIV. In conclusion, dried-yam powder exerts a significant protective effect against cysteamine-induced DU by lowering the activity of inflammatory cytokines and free radicals and restoring the activity of CAs, except in CA IV.

Effects of IY-81149, a newly developed proton pump inhibitor, on gastric acid secretion in vitro and in vivo.

The inhibitory effects of IY-81149 (2-[[(4-methoxy-3-methyl)-2- pyridinyl]methyl-sulfinyl]-5-(1H-pyrol-1-yl)-1H-benzimidazole, CAS 172152-36-2), a newly developed proton pump inhibitor (PPI) on gastric acid secretion were investigated in vitro and in vivo. In rabbit parietal cell preparation, IY-81149 irreversibly inhibited H+/K(+)-ATPase in dose-dependent manner with an IC50 of pump inhibitory activity of 6.0 x 10(-6) mol/l and that of omeprazole (CAS 73590-58-6) was 1 x 10(-4) mol/l at pH 7.4. On cumulation of 14C-aminopyrine in histamine stimulated parietal cells, the IC50 of IY-81149 was 9.0 x 10(-9) mol/l and that of omeprazole was 1.9 x 10(-8) mol/l. The inhibition rates of IY-81149 and omeprazole at a concentration of 1 x 10(-9) mol/l in human parietal cells were 137% and 64%, respectively. In pylorus-ligated rats, IY-81149 showed a 2-3 times stronger inhibitory activity than omeprazole against gastric acid secretion. The ED50 of IY-81149 and omeprazole administered intraduodenally was 1.6 mg/kg and 3.8 mg/kg. In the case of oral administration, the ED50 of IY-81149 and omeprazole was 1.94 mg/kg and 5.64 mg/kg, respectively. But after 24 h administration, the anti-secretory activity of IY-81149 was lower than that of omeprazole at all doses tested. In anesthetized rats, IY-81149 dose-dependently increased gastric pH which was lowered by histamine infusion. In the case of i.v. injection, the ED50 of IY-81149 and omeprazole was 1.2 and 1.4 mg/kg and in the case of i.d. administration, the ED50 of IY-81149 and omeprazole was 3.9 and 4.1 mg/kg, respectively. IY-81149 also significantly inhibited pentagastrin-stimulated gastric secretion. Its ED50 was 2.1 mg/kg and that of omeprazole was 3.5 mg/kg with i.d. administration. In the case of i.v. injection, IY-81149 was equipotent to omeprazole. IY-81149 also inhibited gastric acid secretion strongly in fistular rats. The ED50 of IY-81149 administered intraduodenally was 0.43 mg/kg and that of omeprazole was 0.68 mg/kg. In Heidenhain pouch dogs, the acid output was completely blocked at 0.3 mg/kg, 135 min after i.v. administration. Omeprazole showed a similar effect as IY-81149. The histamine induced increase of acid output in the Heidenhain pouch dog was blocked by 71% 150 min after oral administration of enteric-coated IY-81149 at a dose of 3 mg/kg, and omeprazole showed similar effects. In conclusion, IY-81149 revealed the characteristics as a strong proton pump inhibitor, and its potency against gastric acid secretion was superior to that of the reference drug, omeprazole.

Effects of Achillea wilhelmsii on rat′s gastric acid output at basal, vagotomized, and vagal-stimulated conditions

Background:Achillea is a plant widely used in traditional medicine for gastrointestinal disorders. There are some reports on gastrointestinal effects of Achillea, such as antiulcer, antibacterial, hepatoprotective, choleretic, and antispasmodic. To investigate the effects of aqueous–ethanol extract of Achillea wilhelmsii on rat’s gastric acid output in basal, vagotomized (VX), and vagal-stimulated conditions.Materials and Methods:24 male Wistar rats were randomly divided into 2 groups: control and test. Gastroduodenostomy was performed for each rat. Gastric content was collected for 30 min by washout technique. One milliliter of 3 doses (0.5, 1, and 2 mg/kg) was introduced into the stomach of each rat in the test group and the same volume of saline was used in the control group. Total titratable acid was measured by a titrator.Results:The extract inhibited acid output significantly in basal condition by 1 and 2 mg/kg doses (P < 0.05) but in VX condition this inhibitory effect on acid output disappeared and the 1 and 2 mg/kg doses increased acid output significantly (P < 0.05 and P < 0.001, respectively). The extract showed a reduction in the acid output in vagal-stimulated condition by 1 and 2 mg/kg doses, which were not statistically significant.Conclusion:These results showed an inhibitory effect of A. wilhelmsii extract on acid output in basal condition. The inhibitory effect of the extract was exerted via gastric vagal parasympathetic nerve.

Stimulation of gastric acid secretion and intestinal motility by Vernonia amygdalina extract

Aqueous extract of Vernonia amygdalina infused intragastrically at a dose of 10 mg/ml to rats induced a significant increase in acid output which was reduced by, ranitidine (5 mg/kg b.w.) or atropine (1.2 μMol/kg b.w.). Moreover the extract evoked a dose-dependent contraction of the guinea pig ileum at a dose range of 0.6 mg/ml to 66 mg/ml which was inhibited by atropine (2.4 × 10 − 8 –2.4 × 10 − 6 M).

Time Trends of Ulcer Mortality in Europe

The aim of the present study was to follow the time trends of ulcer disease in a representative sample of European countries and assess whether the most recent behavior of peptic ulcer still fits the overall pattern governed by an underlying birth-cohort phenomenon. Mortality data from 6 countries between 1921 and 2004 were analyzed, including Denmark, France, Germany, The Netherlands, Spain, and Switzerland. The age-specific death rates of gastric and duodenal ulcers from each individual country were plotted as period-age and cohort-age contours. The data from the past 50-80 years show striking similarities among the 6 European countries. In all countries alike, the risk of dying from gastric and duodenal ulcer increased among consecutive generations born during the second half of the 19th century until shortly before the turn of the century, and then decreased in all subsequent generations. The time trends of gastric ulcer preceded those of duodenal ulcer by 10-30 years. The increase in nonsteroidal anti-inflammatory drug consumption or introduction of potent antisecretory medications have not affected the long-term downward trends of ulcer mortality. The birth-cohort pattern has continued to influence the temporal variations of peptic ulcer until most recently. The unique shape of the birth-cohort patterns of gastric and duodenal ulcers and their identical appearance in countries with different health care systems and varying political and socioeconomic histories reflect the overriding influence of Helicobacter pylori infection.

Basis of Decreased Risk of Gastric Cancer in Severe Atrophic Gastritis with Eradication of Helicobacter pylori

Helicobacter pylori infection induces chronic gastritis and lowers gastric juice ascorbic acid concentrations. We investigated how H. pylori eradication affected multiple variables that could prevent or delay development of new or occult gastric cancer in patients with early gastric cancer treated by endoscopic mucosal resection. Gastric juice pH, nitrite concentrations, and total vitamin C concentrations, serum concentrations of vitamin C and specific H. pylori antibody, and intensity of neutrophil infiltration in gastric mucosa were determined before and after successful H. pylori eradication. Successful eradication increased acid output and ascorbic acid secretion into gastric juice, accompanied by disappearance of polymorphonuclear infiltration from the surface epithelium and decreased gastric juice nitrite concentrations. Our data suggest that H. pylori eradication decreases the nitrosation rate as the ratio of vitamin C to nitrite increases. This decreases reactive oxygen species and nitric oxide, eliminating their damaging effect on DNA and reducing cell turnover.

Necessity of intracellular cyclic AMP in inducing gastric acid secretion via muscarinic M 3 and cholecystokinin 2 receptors on parietal cells in isolated mouse stomach

The existence of a direct action of acetylcholine and gastrin on muscarinic M 3 and cholecystokinin 2 (CCK 2) receptors on gastric parietal cells has not yet been convincingly established because these stimulated acid secretions are remarkably inhibited by histamine H 2 receptor antagonists. In the present study, we investigated the necessity of intracellular cyclic AMP in inducing gastric acid secretion via muscarinic M 3 and CCK 2 receptors on parietal cells using an isolated mouse stomach preparation. Bethanechol (10–300 μM) produced a marked increase in acid output and this increase was completely blocked by famotidine (10 μM). In the presence of famotidine, bethanechol (1–30 μM) augmented the acid secretory response to dibutyryl AMP (200 μM) in a concentration-dependent manner. The augmentation was blocked by atropine (1 μM), 4-DAMP (0.1 μM), a muscarinic M 3-selective antagonist, and by Ca 2+ exclusion from the serosal nutrient solution. Pentagastrin (0.3–3 μM) also concentration-dependently stimulated gastric acid secretion, but the effect was completely inhibited by famotidine. In the presence of famotidine, pentagastrin (0.1–0.3 μM) elicited a definite potentiation of the acid secretory response to dibutyryl cyclic AMP (200 μM). This potentiation was inhibited by YM022 (1 μM), a CCK 2 receptor antagonist, and by exclusion of Ca 2+ from the serosal nutrient solution. The present results suggest that gastric acid secretion via the activation of muscarinic M 3 and CCK 2 receptors on the parietal cells is induced by activation of the cyclic AMP-dependent secretory pathway.

Somatostatin‐receptor 2 (sst2)‐mediated effects of endogenous somatostatin on exocrine and endocrine secretion of the rat stomach

Somatostatin is a potent inhibitor of gastric acid secretion. Its effects are mediated through five specific receptor subtypes (sst(1-5)), of which sst(2) is dominant on the enterochromaffin-like (ECL) cell and the parietal cell. To study the paracrine mechanisms of somatostatin, the sst(2)-specific antagonist PRL-2903 was used. Effects of PRL-2903 on acid secretion and release of histamine were studied in the totally isolated, vascularly perfused rat stomach. Further, the release of histamine and gastrin after bombesin, alone and in combination with PRL-2903, were studied. Results are presented as mean+/-standard error of the mean (s.e.m.). PRL-2903 concentration-dependently increased the venous histamine concentration from basal 55.6+/-7.5 to 367+/-114 nM at 50 microM PRL-2903. With 10 microM PRL-2903, venous histamine output increased from baseline 6.2+/-0.5 to 20.9+/-4.9 nmol h(-1); P=0.008. The combination of 520 pM gastrin and 10 microM PRL-2903 increased venous histamine output from 41.7+/-7.3 nmol h(-1) with gastrin alone to 95.2+/-9.8 nmol h(-1); P=0.016. Further, 10 microM PRL-2903 increased acid output from baseline 8.5+/-1.8 to 37.4+/-11 micromol h(-1); P=0.017. When combined with 10 microM ranitidine, PRL-2903 did not significantly stimulate acid secretion. Bombesin/PRL-2903 increased venous histamine concentration from 50.4+/-14.8 to 292+/-64.2 nM; P=0.008, and gastrin concentration from 38.6+/-13.1 to 95.8+/-20.3 pM; P=0.037. Endogenous somatostatin exerts a continuous restraint on histamine and gastrin release from the gastric mucosa and significantly reduces baseline acid secretion.

The Prevalence of Helicobacter pylori Infection and the Pattern of Gastritis in Barrett’s Esophagus

Background/Aim: Acid output is related to the gastritis pattern in Helicobacter pylori infection. The hypothesis to be tested is that gastritis in patients with Barrett’s esophagus, defined as columnar epithelia lined lower esophagus (CELLO) with intestinal metaplasia (IM), is antrum predominant. Patients and Methods: Patients undergoing esophagogastroduodenoscopy were investigated for CELLO. The gastritis parameters H. pylori density, activity, and chronicity were graded in biopsy specimens of antrum and corpus. IM was assessed in biopsies from CELLO patients. In a prospective part, 19 patients with CELLO with IM were compared with 38 age-matched control patient with dyspepsia. Results: Of 200 patients with CELLO, 85% had a short segment (<3 cm), 15% a segment of ≧3 cm. IM was present in 36% of cases with a short CELLO and in 84% of patients with a long segment. The H. pylori prevalence was 50%, independent of the length of CELLO or the presence of IM. The gastritis phenotype was minimally antrum predominant. The antrum/corpus distribution was not related to the length of CELLO or the presence of IM and not different from controls. The activity in corpus and antrum was lower in patients with CELLO with IM as compared with patients with CELLO without IM or controls. Conclusions: A high proportion of patients with CELLO are H. pylori infected. The pattern of H. pylori gastritis is characterized by a pangastritis with low activity which is not likely to predispose to an increase in acid output after eradication.

Helicobacter pylori infection of rhesus monkeys is associated with down-regulation of H, K-ATPase a subunit mRNA

Clinical studies and data from isolated gastric parietal cells suggest that acid secretion is inhibited by acute H pylori infection, leading to gastric hypochlorhydria. In addition, eradication of H. pylori is associated with increased acid secretion. The mechanism of these changes is unknown. Gastric acid secretion is mediated by the enzyme H,K-ATPase which exchanges luminal K+ for cytoplasmic H+. To test the hypothesis that H pylori infection has direct inhibitory effects on gastric H,K-ATPase a subunit (HKa) gene expression, we sought a correlation between H pylori infection and levels of HKa messenger RNA. Total RNA was isolated from gastric corpus biopsies of three rhesus monkeys (Macaca mulatta) with persistent H pylori infection and four uninfected monkeys. A 2I7 bp HKa cDNA template was made from monkey RNA using RT-PCR with primers based on human HKa cDNA. Using RNA polymerase, a 32p_ labeled anti-sense RNA was generated from the monkey HKa cDNA template. Relative HKa mRNA concentrations in the monkey gastric RNA samples were measured by ribonuclease protection assay (RPA), using measurement of constitutively-expressed 18S ribosomal RNA in the same samples to normalize the data. The radiographic intensities of HKa mRNA bands and of 18S rRNA bands on RPA phosphor imager electrophoretograms were quantitated by digital analysis. Gastric HKa mRNAlI8S rRNA band intensity ratios were consistently higher in biopsies from uninfected monkeys compared to persistently-infected animals. These results suggest that persistent H pylori infection of monkey gastric mucosa inhibits HKa synthesis by parietal cells, reducing cellular levels of functional H,KATPases and thus decreasing acid output. Assuming that these effects are reversible after treatment, the present observations also could explain the increased acid output observed in humans following eradication of H pylori. as well as the increased risk for gastroesophageal reflux disease associated with H. pylori eradication.

Inhibitory effect of the cannabinoid receptor agonist WIN 55,212-2 on pentagastrin-induced gastric acid secretion in the anaesthetized rat.

The effect of the cannabinoid (CB) receptor agonist WIN 55,212-2 on gastric acid secretion was studied in the anaesthetized rat after stimulation with pentagastrin. WIN 55,212-2 (0.5-2 mg/kg, i.v.) was inactive on basal secretion but caused a marked inhibition (80%) of the acid secretion stimulated by pentagastrin (10 microg/kg, i.v.). The enantiomer WIN 55,212-3 (1-3 mg/kg, i.v.) did not significantly modify basal or pentagastrin-induced acid secretion. The inhibitory effect of WIN 55,212-2 against pentagastrin was prevented by the administration of the selective cannabinoid CB1 receptor antagonists SR141716A (1 mg/kg, i.v.) and LY320135 (1 mg/kg, i.v.); by contrast, the CB2 receptor antagonist SR144528 (0.3-1 mg/kg, i.v.) was without effect. The selective CB2 receptor agonist JWH-015 (0.1-10 mg/kg, i.v.) was inactive on the increase of acid output stimulated by pentagastrin. These results suggest that the inhibitory effect of WIN 55,212-2 on pentagastrin-stimulated acid secretion in the anaesthetized rat is mediated by specific cannabinoid receptors. Moreover, the antagonism of WIN 55,212-2-induced effects by the selective CB1 receptor antagonists SR141716A and LY320135 together with the ineffectiveness of both the CB2 receptor agonist JWH-015 and the CB2 receptor antagonist SR144528 indicate that CB1 receptor subtypes are predominantly involved in the antisecretory effect of WIN 55,212-2.

CCK 1 and CCK 2 receptors regulate gastric pepsinogen secretion

The present study investigated (1) the pharmacological profile of cholecystokinin (CCK) receptor subtypes involved in the regulation of gastric pepsinogen secretion, (2) the influence of gastric acidity on peptic responses induced by CCK-8-sulfate (CCK-8S) or gastrin-I; and (3) the mechanisms accounting for the effects of CCK-like peptides on pepsinogen secretion. In anaesthetized rats, i.v. injection of CCK-8S or gastrin-I increased both pepsinogen and acid secretion. The pepsigogue effect of CCK-8S was higher than that of gastrin-I, whereas acid hypersecretion after CCK-8S was lower than that induced by gastrin-I. Peptic output following CCK-8S was partly blocked by i.v. injection of the CCK 1 receptor antagonist, devazepide (−75.3%), or the CCK 2 receptor antagonist, l-365,260 [3 R(+)- N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1 H-1,4-benzodiazepine-3yl)- N′-(3-methyl-phenyl)urea; −27.9%], but was fully prevented by combined administration of devazepide and l-365,260. The gastric acid hypersecretory effect of CCK-8S was enhanced by devazepide (+84.5%) and blocked by l-365,260. In contrast, the gastric secretory actions of gastrin-I were insensitive to devazepide, but abolished by l-365,260. Excitatory effects of CCK-8S and gastrin-I were not modified by vagotomy or atropine, whereas cimetidine or α-fluoromethylhistidine (irreversible blocker of histidine decarboxylase) partly prevented acid hypersecretion induced by both peptides without affecting their pepsigogue effects. After pretreatment with omeprazole, both CCK-8S and gastrin-I failed to stimulate acid secretion, while they increased pepsinogen output. In rats with gastric perfusion of acid solutions, CCK-8S or gastrin-I increased peptic output in a pH-independent manner either with or without pretreatment with omeprazole. Ablation of capsaicin-sensitive sensory nerves as well as application of lidocaine to the gastric mucosa failed to modify the excitatory effects of CCK-8S or gastrin-I on pepsinogen and acid secretion. Blockade of the nitric oxide (NO) synthase pathway by N G-nitro- l-arginine-methyl ester prevented the pepsigogue actions of both CCK-8S and gastrin-I (−61.8% and −71.7%, respectively), without affecting the concomitant increase in acid output. In addition, both these peptides significantly increased the release of NO breakdown products into the gastric lumen. The present results suggest that: (1) both CCK 1 and CCK 2 receptors mediate the peptic secretory responses induced by CCK-like peptides; (2) the excitatory inputs of CCK-8S and gastrin-I to chief cells are not driven through acid-dependent mechanisms or capsaicin-sensitive afferent sensory nerves; and (3) under in vivo conditions, the stimulant actions of CCK-like peptides on pepsinogen secretion are mediated, at least in part, by an increase in NO generation.

Rebound hypersecretion after omeprazole and its relation to on-treatment acid suppression and Helicobacter pylori status

Background & Aims: There have been conflicting reports regarding acid secretion after treatment with omeprazole. This study examined acid secretion after treatment with omeprazole and its relation to Helicobacter pylori status and on-treatment gastric function. Methods: Twelve H. pylori–negative and 9 H. pylori–positive subjects were examined before, on, and at day 15 after an 8-week course of 40 mg/day omeprazole. On each occasion, plasma gastrin, intragastric pH, and acid output were measured basally and in response to increasing doses of gastrin 17. Results: In the H. pylori–negative subjects at day 15 after omeprazole treatment, basal acid output was 82% higher ( P < 0.007) and maximal acid output 28% higher ( P < 0.003) than before omeprazole. The degree of increase in maximal acid output was related to both on-treatment pH and on-treatment fasting gastrin levels, being 48.0% in subjects with an on-treatment pH of >4 vs. 21.0% in those with a pH of <4 ( P < 0.02) and 49.2% in subjects with an on-treatment gastrin of >25 ng · L −1 vs. 19.8% in those with a fasting gastrin of <25 ng · L −1 ( P < 0.006). At day 15 after omeprazole treatment, the H. pylori–positive subjects showed a heterogeneous response with some having increased acid output and others persisting suppression. Conclusions: Rebound acid hypersecretion occurs in H. pylori–negative subjects after omeprazole treatment. Its severity is related to the degree of elevation of pH on treatment. Persisting suppression of acid secretion masks the phenomenon in H. pylori–positive subjects. GASTROENTEROLOGY 1999;116:239-247

Effect of somatostatin immunoneutralization on gastric acid and pancreatic enzyme secretion in anesthetized rats

The involvement of somatostatin in urethane-anesthesia-evoked suppression of gastric acid secretion has been described. The present study has examined the role of endogenous somatostatin in diminished pancreatic enzyme secretion during anesthesia, while monitoring acid secretion concurrently. Rats were anesthetized with either urethane or sodium pentobarbital. An indwelling catheter was placed into the right jugular vein. The esophagus and the pylorus were ligated, and the stomach was perfused with saline. The common bile duct was ligated at the hepatic hilum, and cannulated at the duodenal end of the duct for collecting pure pancreatic juice. Purified somatostatin monoclonal antibody (CURE.S6) or control antibody (keyhole limpet hemacyanin, KLH) was injected iv in increasing doses (0.05; 0.15; 0.5; and 1.5 mg) every 30 min ( n = 6). Gastric acid and pancreatic amylase secretions were measured. The effect of the antibodies on CCK-8-stimulated (0.25–2.50 nmol/kg/h) pancreatic amylase secretion was also tested. During urethane anesthesia somatostatin antibody induced a dose-dependent increase in acid output, while control antibody did not change it. Basal pancreatic amylase secretion was not affected by either somatostatin or by control antibody. Pancreatic secretory responses to high but not to low doses CCK-8 were found to be significantly increased following immunoneutralization of somatostatin. In sodium pentobarbital-anesthetized rats somatostatin antibody stimulated basal acid secretion but did not affect basal pancreatic amylase secretion. Our data indicate that in anesthetized rats endogenous somatostatin mediates suppression of basal gastric acid secretion but not that of basal pancreatic amylase secretion, and this action does not depend on the type of anesthesia. Furthermore, endogenous somatostatin may play a physiological role in modulating stimulated pancreatic enzyme secretion in this species.

Gastric ECL-cell hyperplasia produces enhanced basal and stimulated gastric acid output but not gastric erosion formation in the rat

1. 1. The purpose of this study was to examine the change in gastric acid output and gastric erosion formation produced by inducing gastric enterochromaffinlike (ECL) cell hyperplasia in female rats. 2. 2. Rats were treated with vehicle or ranitidine (1,200 μmol/kg/day×4 wks) administered via SC Alzet minipumps. Experiments were performed 24 hours after removing the minipump, when the inhibitory effect of ranitidine on gastric acid secretion had been lost. 3. 3. Basal gastric acid secretion was 7-fold higher in chronic ranitidine animals than in sham control. 4. 4. Both total and net gastric acid secretions stimulated by carbachol/pentagastrin infusion or histamine injection were significantly higher in chronic ranitidine animals than in controls. 5. 5. By contrast, intracisternal injection of the chemical vagal stimulant RX77368 (100 ng) resulted in no net increase in acid output of the recovered ranitidine-pretreated group. 6. 6. No significant changes in gastric erosions produced experimentally by cold exposure plus restraint or indomethacin pretreatment were noted in recovered chronic ranitidine animals compared to sham controls. 7. 7. These findings suggest that achlorhydria-induced ECL cell hyperplasia augments both basal and stimulated gastric acid secretory function. The histamine results implicate an enhanced parietal cell mass, upregulation of H 2 receptors, and/or second-messenger events at the parietal cell as the mechanism for the enhanced gastric secretory response.

Central vagal activation increases mucus gel thickness and surface cell intracellular pH in rat stomach

BACKGROUND & AIMS: Central vagal stimulation induced by the thyrotropin- releasing hormone analogue RX 77368 injected intracisternally in urethane-anesthetized rats is gastroprotective. In an in vivo system, the effects of central RX 77368 on discrete components of the rat gastric mucosal barrier were studied to determine if these effects were prostaglandin synthesis dependent.METHODS: Using intravital microscopy, intracellular pH of gastric surface cells, mucus gel thickness, gastric mucosal blood flow, and acid output were measured simultaneously in vivo.RESULTS: Intracisternal RX 77368 significantly increased acid output, gel thickness, and blood flow. Indomethacin enhanced the RX 77368-induced increase in acid output but had no effect on measures of gastric defense during mucosal superfusion with neutral solutions. During acid superfusion, RX 77368 delayed acidification and enhanced recovery of surface cell intracellular pH. These latter effects were reversed partially by indomethacin. Omeprazole abolished RX 77368-induced acid secretion but did not alter its effects on gastric defense mechanisms.CONCLUSIONS: In response to central vagal stimulation with RX 77368, gastric defense mechanisms were enhanced through prostaglandin-dependent and -independent pathways, in contrast to the prostaglandin-independent effects of intravenous pentagastrin. RX 77368-induced enhancements of gastric defense mechanisms did not occur as a result of acid secretion.(Gastroenterology 1997 Feb;112(2):409-17)

Somatostatin sst2 receptor-mediated inhibition of parietal cell function in rat isolated gastric mucosa.

1. The aim of this study was to determine the location and functional characteristics of the somatostatin (SRIF) receptor type(s) which mediate inhibition of acid secretion in rat isolated gastric mucosa. 2. Gastrin (1 nM-1 microM), dimaprit (10 microM-300 microM) and isobutyl methylxanthine (IBMX, 1 microM-100 microM) all caused concentration-dependent increases in acid output. Responses to gastrin were almost completely inhibited by ranitidine (10 microM) at a concentration which abolished the secretory response to dimaprit. In contrast, responses to IBMX were not changed by ranitidine suggesting that IBMX acts directly on the parietal cell and not indirectly by releasing histamine from enterochromaffin-like (ECL) cells. 3. SRIF-14 (1 nM-1 microM) had no effect on basal acid output, but inhibited acid output produced by gastrin, dimaprit and IBMX in a concentration-dependent manner with respective EC50 values of 46, 54 and 167 nM. The peptidase inhibitors, amastatin (10 microM) and phosphoramidon (1 microM), had no effect on SRIF-induced inhibition of dimaprit stimulated gastric acid secretion. 4. The inhibitory effect of a range of SRIF analogues on gastrin-, dimaprit- and IBMX-induced acid secretion was also studied. Irrespective of the secretagogue used to increase acid output, the rank order of potencies was similar (BIM-23027 = seglitide = octreotide > SRIF-14 = SRIF-28 > L-362,855). The linear peptide BIM-23056 was devoid of agonist or antagonist activity in concentrations up to 1 microM. 5. The sst2 receptor selective peptides, BIM-23027, seglitide and octreotide were the most potent inhibitors of gastrin-, dimaprit- and IBMX-induced acid secretion suggesting that SRIF receptors resembling the recombinant sst2 receptors are involved. Furthermore, since dimaprit and IBMX stimulate gastric acid secretion independently of histamine release, sst2 receptor-mediated inhibition must occur at the level of the parietal cell itself.