Gastric Pepsin Secretion Research Articles

Marjoram increases basal gastric acid and pepsin secretions in rat

Considering the high consumption rate of marjoram in the Iranian population, this study was designed to investigate the effects of marjoram extract on gastric acid and pepsin secretion. In this study, Wistar rats (n=12) were divided into two equal case and control groups. Under general anaesthesia with 50 mg/kg i.p. sodium thiopental, laparatomy was done and a cannula inserted in the duodenum. In the case animals marjoram (12.5 mg/kg) was injected into the stomach through the mentioned cannula. The gastric contents were collected by the wash-out technique. Acid and pepsin secretions were then measured by titration and the Anson method, respectively. In the marjoram group, basal acid and pepsin secretions were significantly increased compared with the control group (acid: 20+/-3.36 vs 4.1+/-0.36 micromol/15 min; pepsin: 9.04+/-0.01 vs 5.62+/-0.12 microg/15 min; p<0.001). In the control group, pentagastrin stimulation increased acid secretion in comparison with the basal level (10.14+/-1.34 vs 4.1+/-0.36 micromol/15 min, p<0.001), while in the marjoram group, there was a significant decline (16.46+/-3.23 vs 20+/-3.36 micromol/15 min, p<0.001). In the marjoram group pentagastrin increased pepsin secretion in comparison with the basal state (12+/-0.11 vs 9.04+/-0.1 microg/15 min, p<0.001). It seems that marjoram contains some components that activate chief and parietal cells and increase basal acid and pepsin secretion.

The effect of chronic consumption of paraoxon on basal and pentagastrin-stimulated gastric acid and pepsin secretion in rats

Paraoxon, an organophosphate metabolite of the insecticide parathion inhibits the enzyme, acetylcholinesterase (Achase). Organophosphates affect the heart, visual system, nervous system and muscles. In this present study, we investigate the effects of the chronic consumption of paraoxon on gastric acid and pepsin secretion in N-mari rats. This study was performed from April 2003 to May 2004 in the Physiology department of Baghiatalah University of Medical Sciences, Tehran, Iran. It was performed on three groups of female N-mari rats (10 /group) each weighing 200-250 g. The first group received 0.05 mg/kg/day paraoxon subcutaneously for one month. The second group received the same chronic doses of ethyl alcohol (96%) (solvent of paraoxon) and the third group (control) received no drugs. After tracheostomy and laparatomy, gastric secretions were collected with a tube via the duodenum. Pentagastrin (25 microg/kg, i.p.) was used as a gastric stimulator. Acid and pepsin secretions were measured by titration and the Anson method, respectively. The stages of the measurements were basal (first and second), stimulated and returned-basal. Basal acid secretion in the paraoxon group was greater than those in the alcohol and control groups (14.61 +/- 1.46, 7.18 +/- 0.28 and 7.88 +/- 0.26 micromol/15 min, respectively, P < 0.001)). Although pentagastrin-stimulated acid secretion in all the three groups was greater than that of the basal state, there were no significant differences among the three groups. Basal pepsin secretions in the paraoxon group were greater than those in the alcohol and control groups (2.97 +/- 0.32, 1.19 +/- 0.25 and 0.55 +/- 0.06 microg/15 min, respectively). Pentagastrin-stimulated pepsin secretion in the paraoxon group was significantly greater than those in the alcohol and control groups (3.22 +/- 0.38, 2.22 +/- 0.46 and 1.09 +/- 0.66 microg/15 min, respectively, P < 0.001). Chronic exposure to paraoxon results in the increased secretion of gastric acid and pepsin.

Investigation of the Mechanisms Underlying the Gastroprotective Effect of Nicorandil

Aim: This study investigated possible mechanisms underlying the gastroprotective effect of nicorandil on experimentally-induced gastric lesions in rats. Methods: Rats were randomly assigned to vehicle-, nicorandil (10 mg/kg)-, glibenclamide (6 mg/kg)-, nicorandil + glibenclamide- and cimetidine-pretreated groups, in addition to non-stressed control group, to demonstrate whether the K_ATPchannel opening contributed to nicorandil’s gastroprotection. Lesions were induced by water immersion-restraint stress (WIRS) and ulcer indices were determined. Gastric juice parameters (pH, acid output, pepsin and mucin concentrations) were determined. Another set of rats was divided into control, saline-pretreated and nicorandil (10 mg/kg)-pretreated groups. Rats underwent WIRS and their stomachs were used for determination of gastric mucosal lipid peroxides, histamine, PGE₂, and total nitrites levels. Results: Nicorandil displayed significant protection against gastric lesions formation, abolished by concomitant administration of glibenclamide. Nicorandil significantly reduced gastric acid and pepsin secretion, but upon coadministration with glibenclamide, these effects were blocked. Additionally, nicorandil significantly reduced gastric mucosal lipid peroxides and total nitrites, but did not affect PGE₂ and histamine levels. Conclusion: Results confirm a gastroprotective effect for nicorandil, the mechanism of which comprises K_ATP channel opening, free radical scavenging, decrease of pepsin and acid secretion and prevention of the detrimental rise in nitric oxide during WIRS.

In vitroeffects of ghrelin on gastric H+-K+-ATPase and pepsin activity and mRNA expression of gastrin, somatostatin, receptors for GH and IGF-1 in cultured gastric mucosal cells of weanling piglets

AbstractThe present study was conducted to investigate the effects of ghrelin on gastric acid and pepsin secretion, as well as the mRNA expression of gastrin, somatostatin (SS) and receptors for growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in gastric mucosal cells in vitro. Gastric mucosal cells were isolated from 5-week-old weanling piglets and exposed for 4 h to 3×10−2, 3×10−1, 3, 3×10 and 3×102nmol/l of h-ghrelin, respectively after 30-h incubation in DMEM/F-12. Pepsin activity in culture medium, cell viability and H+-K+-ATPase activity, as well as mRNA expression of gastrin, SS, GHR and IGF-1R in gastric mucosal cells were determined as response criteria. The experiment was repeated three times. Ghrelin significantly (P&lt;0·05) increased H+-K+-ATPase activity of gastric mucosal cells at 3×10−1, 3 and 3×10 nmol/l of h-ghrelin. However, no significant changes were observed either in pepsin activity or the cell viability after ghrelin treatment. The mRNA expression of gastrin and SS was significantly increased in gastric mucosal cells exposed to h-ghrelin at 3×10−1and 3 nmol/l (P&lt;0·05). H-ghrelin significantly increased IGF-1R but not GHR mRNA expression at 3×10−1, 3 and 3×10 nmol/l of h-ghrelin (P&lt;0·05). Ghrelin acts on gastric mucosal cells from weanling piglets to regulate the H+-K+-ATPase activity and mRNA expression of gastrin, SS, and IGF-1Rin vitro.

Effect of acid secretion blockade on acute gastric mucosal lesions induced by Tityus serrulatus scorpion toxin in anaesthetized rats

Scorpion venom (TX) promotes gastric acid and pepsin secretion leading to acute gastric mucosal lesions (AGML), when injected in animals. The goal of the present study was to observe the effects of acid gastric secretion blockers over the incidence of TX-induced AGML in vivo. To verify this model, we used male albino rats, fasted 18–20 h ( n = 122 ) and anaesthetized with urethane (1.4 g/kg, i.p.). Their trachea and left femoral vein were both cannulated; the first to avoid airway obstructions during scorpion intoxication and the second for administration of saline, TX and acid blockers. Following the surgical procedure, the animals were divided in 10 groups of at least 10 animals each. Control groups were injected with NaCl 0.9% 1 ml/kg ( n = 10 ) or TX 375 μg/kg ( n = 32 ). Test groups ( n = 10 , each) received atropine 5 mg/kg, cimetidine 10 mg/kg, ranitidine 2.5 mg/kg, ranitidine 5 mg/kg, omeprazol 1 mg/kg, omeprazol 4 mg/kg, octreotide 80 and octreotide 100 μg/kg 10 min before the TX was injected. After 1 h of intoxication, the stomach was resected for macroscopic study and the gastric secretion was collected for volume, pH and acid output assessment. We observed that all blockers were able to completely or partially prevent the TX-induced acid secretion as well as the AGML ( p < 0.05 ). Our data suggest the TX-induced AGML can be prevented by different class of acid blockers injected before the intoxication.

Antiulcerogenic and ulcer healing effects of Solanum nigrum (L.) on experimental ulcer models: Possible mechanism for the inhibition of acid formation

Solanum nigrum, an herbal plant which is recommended in ayurveda for the management of gastric ulcers. Therefore, the purpose of the study was to investigate the antiulcer effect of Solanum nigrum fruits extract (SNE) on cold restraint stress (CRU), indomethacin (IND), pyloric ligation (PL) and ethanol (EtOH) induced gastric ulcer models and ulcer healing activity on acetic acid induced ulcer model in rats. The treatment with SNE at higher dose significantly inhibited the gastric lesions induced by CRU (76.6%), IND (73.8%), PL (80.1%) and EtOH (70.6%), respectively, with equal or higher potency than omeprazole. SNE showed concomitant attenuation of gastric secretory volume, acidity and pepsin secretion in ulcerated rats. In addition, SNE (200 and 400mg/kgb.w.) accelerated the healing of acetic acid induced ulcers after the treatment for 7 days. Further, to ascertain the antisecretory action, the effects of SNE on H+K+ATPase activity and plasma concentration of gastrin hormone in ulcerated rats were determined. SNE significantly inhibits H+K+ATPase activity and decreases the gastrin secretion in EtOH-induced ulcer model. The severity of the reaction of ulcerogen and the reduction of ulcer size by SNE was evident by histological findings. Toxicity studies of SNE have also been carried out for its safety evaluation. SNE, thus, offers antiulcer activity by blocking acid secretion through inhibition of H+K+ATPase and decrease of gastrin secretion. These results further suggest that SNE was found to possess antiulcerogenic as well as ulcer healing properties, which might also be due to its antisecretory activity.

The effect of insulin-dependent diabetes mellitus on basal and distention-induced acid and pepsin secretion in rat

Background: Diabetes mellitus is one of the most common endocrine diseases and affects most body organs. It affects gastric acid secretion, but this effect has not been fully understood. As the effects of diabetes on gastric pepsin secretion has not been proved yet, in this experimental study basal and distension-stimulated acid and pepsin secretions of diabetic and non-diabetic rats have been compared. Material and methods: Female N-Mari rats weighing 200–250 g were used. Diabetic state was induced by intraperitoneal injection of 75 mg/kg streptozotocin. Animals were anaesthetized by the interaperitoneal injection of 60 mg/kg thiopental sodium. Then tracheostomy and laparotomy were done and gastric secretions were collected by a cannula entered via duodenum. Gastric distention induce by 1.5 ml normal saline per each 100 g of body weight in stomach. Acid and pepsin were measured by titration and Anson’s method, respectively. Results: Basal gastric secretions were similar in diabetic and non-diabetic animals. Distention-stimulated acid secretions in diabetic and non-diabetic rats were 3.24±0.16 and 8.05±0.21 μmol/15 min, respectively, which were significantly different ( P=0.00001). Distention-induced pepsin secretion in diabetic and non diabetic rats were 3.16±0.13 and 5.24±0.16 μg/15 min, respectively, which were significantly different ( P=0.00001). Conclusion: In this study the stomach of diabetic animals showed less reaction to distention, which may be due to the reduction of acid and pepsin secretary cells, reduction of the function of the cells, gastric atrophy or gastric vagus neuropathy. These probabilities need to be examined.

Effects of Aloe preparation on the histamine-induced gastric secretion in rats

The effects of Aloe preparation containing 80% Aloe gel on the gastric acid, pepsin and mucus secretion were evaluated in histamine-induced gastric fistula model in rats by comparison to the effects of placebo and fresh Aloe gel. Aloe preparation and placebo at a dose of 8 ml/kg inhibited gastric acid but stimulated pepsin secretory rates. On the other hand, fresh Aloe gel at a dose of 6.4 ml/kg prolonged histamine stimulatory effects on the gastric acid secretion while it inhibited gastric pepsin secretion. Both Aloe preparation and placebo increased soluble mucus secretory rate in a dose-dependent manner whereas fresh Aloe gel had no effect. The Aloe preparation and placebo at a dose of 8 ml/kg increased the gastric visible mucus content while fresh Aloe gel slightly increased the visible mucus content. This study reveals that fresh Aloe gel prolonged the effects of histamine-stimulated acid secretion and inhibits pepsin secretion in histamine-treated rats. The Aloe preparation inhibited gastric acid, stimulated pepsin and mucus secretion. However, there were no difference in the secretory rates of Aloe preparation and placebo-treated rats at the same doses. This result indicates that the observed effects of Aloe preparation was mostly due to other compositions of the preparation rather than Aloe gel itself. Since the highest dose of Aloe gel preparation used in the present study was limited by the volume of the instillated solution in gastric fistula model, the effects of Aloe vera gel were not able to be observed in the present study might be due to the inadequate dose of the preparation.

Effect of Thyroid Hormones on Distension-Induced Gastric Acid and Pepsin Secretions in Rats

Thyroid hormones are known to influence acid and pepsin secretion, though the exact mechanism is not fully understood. In this study, distension-stimulated acid and pepsin secretions in hypo- and hyperthyroid rats were compared with controls. Each group consisted of 8 N-mari rats of both sexes, weighing 246.6+/-9.2 g. Hypo- and hyperthyroid states were induced by administration of methimazole (500 mg/L H2O) and thyroxin (200 microg/L H2O) respectively, in drinking water. All animals were deprived of food, but not of water 24 hours before the experiments. After anesthetization with sodium thiopental (50 mg/kg body weight, ip), tracheotomy and laparatomy, gastric secretions were collected through a cannula introduced via the duodenum. Gastric distension was induced by the injection of Ringer solution in stomach (1.5 cm(3)/100 g body weight). Acid secretions, which were measured by automatic titrator in the hypothyroid, hyperthyroid and control groups were 8+/-0.2, 14.6+/-1.9 and 10.2+/-0.1 micromol/15 min, respectively. Pepsin secretions were 4.4+/-0.5, 9.09+/-0.4 and 6.1+/-0.1 mg/15 min. in respective groups. There were statistically significant differences in both series between control and the other two groups. The results from the measurements of thyroid-stimulating hormones and T4 hormones showed that increased or decreased thyroid function can significantly affect gastric distension-induced acid and pepsin secretion.

Protease-activated receptor-2 (PAR-2) in the rat gastric mucosa: immunolocalization and facilitation of pepsin/pepsinogen secretion.

1. Agonists of protease-activated receptor-2 (PAR-2) trigger neurally mediated mucus secretion accompanied by mucosal cytoprotection in the stomach. The present study immunolocalized PAR-2 in the rat gastric mucosa and examined if PAR-2 could modulate pepsin/pepsinogen secretion in rats. 2. PAR-2-like immunoreactivity was abundant in the deep regions of gastric mucosa, especially in chief cells. 3. The PAR-2 agonist SLIGRL-NH(2), but not the control peptide LSIGRL-NH(2), administered i.v. repeatedly at 0.3 - 1 micromol kg(-1), four times in total, significantly facilitated gastric pepsin secretion, although a single dose produced no significant effect. 4. The PAR-2-mediated gastric pepsin secretion was resistant to omeprazole, N(G)-nitro-L-arginine methyl ester (L-NAME) or atropine, and also to ablation of sensory neurons by capsaicin. 5. Our study thus provides novel evidence that PAR-2 is localized in mucosal chief cells and facilitates gastric pepsin secretion in the rats, most probably by a direct mechanism.

Feedback regulation of pancreatic secretion by peptide YY

The present status of our understanding of the feedback regulation of pancreatic secretion by peptide YY (PYY) released from the distal intestine is reviewed. Exocrine pancreatic secretion is primarily controlled by the cephalic (the vagus nerve), gastric (acid and pepsin secretion, and nutrients delivered into the duodenum by gastric emptying), and intestinal (secretin and CCK) mechanisms. PYY acts on the multiple sites in the brain and gut, and inhibits pancreatic secretion by regulating these primary control mechanisms. The involvement of Y1 and Y2 receptors has been suggested in the regulation of pancreatic secretion. However, it remains to be studied which site of action or receptor subtype is physiologically most important for this regulation.

Long-term lansoprazole control of gastric acid and pepsin secretion in ZE and non-ZE hypersecretors: a prospective 10-year study.

The majority of patients with Zollinger-Ellison syndrome require lifelong treatment with proton pump inhibitors. To determine the efficacy of lansoprazole control of acid and pepsin secretion over the long term in Zollinger-Ellison syndrome and non-Zollinger-Ellison syndrome hypersecretors. Sixty-three hypersecretors (basal acid output > 15 mmol/h), 46 Zollinger-Ellison syndrome and 17 non-Zollinger-Ellison syndrome, with a total history of 15.4 and 19.2 years, respectively, were entered into a long-term prospective study using lansoprazole. Sixty-one were studied every 3 months for 1 year and then every 3-6 months up to 10 years during lansoprazole treatment with endoscopy, serum gastrin and gastric analysis, measuring both basal and stimulated pH and acid and pepsin secretion. Doses were individually optimized and adjusted to keep the basal acid output at < 5 mmol/h in intact patients and < 1 mmol/h in antrectomized Zollinger-Ellison syndrome patients. The dose of lansoprazole could not be predicted a priori from pre-treatment acid or pepsin output, serum gastrin, prior omeprazole dose or diagnosis or prior complications. The median dose was approximately 80 mg/day, with a wide range from 15 mg every other day to 360 mg/day, and generally stabilized by 12 months. However, as doses were adjusted over time for indications, almost half the patients required higher doses. With adjustments, the basal acid output was maintained in the target range in > 90% of intact patients and in 80% of antrectomized patients. Gastric juice pH increased from approximately 1.2 before therapy to > 3.4 during therapy. Serum gastrin in Zollinger-Ellison syndrome patients, after excluding five outliers, did not change over the course of therapy, but doubled in non-Zollinger-Ellison syndrome patients. There were no adverse events due to lansoprazole, and routine laboratory studies remained normal. The dose of lansoprazole for hypersecretors cannot be predicted, and thus needs to be optimized empirically on an individual basis. With continued periodic adjustments, almost half the patients required increased doses, while safe dose reduction was possible in only one-quarter. When individually optimized, lansoprazole proved to be safe and effective in the control of secretion for the treatment of both Zollinger-Ellison syndrome and non-Zollinger-Ellison syndrome hypersecretors for up to 10 years.

Helicobacter pylori and the gastroduodenal mucosa

Surgery 2001;130:13-6.

Phytohaemagglutinin inhibits gastric acid but not pepsin secretion in conscious rats

Phytohaemagglutinin (PHA), a kidney bean lectin, is known for its binding capability to the small intestinal surface. There has been no data available, however, on the biological activity of PHA in the stomach. Recent observations indicate that PHA is able to attach to gastric mucosal and parietal cells. Therefore, we examined whether PHA affects gastric acid and pepsin secretion in rats. Rats were surgically prepared with chronic stainless steel gastric cannula and with indwelling polyethylene jugular vein catheter. During experiments, animals were slightly restrained. Gastric acid secretion was collected in 30 min periods. Acid secretion was determined by titration of the collected gastric juice with 0.02 N NaOH to pH 7.0. Pepsin activity was estimated by measuring enzymatic activity. Saline, pentagastrin and histamine were infused intravenously. PHA or bovine serum albumin (BSA) were dissolved in saline and given intragastrically through the gastric cannula. PHA significantly inhibited basal acid secretion. Inhibition of acid output reached 72% during the first collection period following PHA administration when compared, then gradually disappeared. Pentagastrin-stimulated acid secretion was repressed dose-dependently by PHA as well. Maximal inhibition was observed during the first 30 min following application of PHA. Histamine-stimulated acid secretion was inhibited by PHA in a similar manner. Pepsin secretion was not affected by PHA under either basal or stimulated conditions. These results provide evidence that PHA is a potent inhibitor of gastric acid secretion in conscious rats, but it does not affect pepsin output from the stomach.

Water Extracts of Helicobacter pylori Suppress the Expression of Histidine Decarboxylase and Reduce Histamine Content in the Rat Gastric Mucosa

Background: Acute Helicobacter pylori (Hp) infection in humans may be associated with markedly reduced gastric acid secretion, but the mechanism of this hypochlorhydria has not been fully explained. Aims: This study was designed to investigate how water extracts (WE) of Hp applied on rat gastric mucosa affect gastric secretion and mucosal histamine concentration as well as the gene expression for histamine decarboxylase (HDC), the key enzyme converting histidine to histamine and for interleukin-1β (IL-1β), the important proinflammatory cytokine. Materials and Methods: Wistar rats were surgically equipped with small cannulas to form gastric fistulas (GF). Four weeks after formation of GF, rats received either saline (control group) or WE obtained from type I Hp strain expressing CagA/VacA proteins and from type II Hp strain negative for CagA/VacA. Hp-WE was applied intragastrically (i.g.) in a volume of 1 ml at days 0, 2, 4 and 6 (total 4 times). At days 7 and 14, the secretory tests were performed during which basal gastric acid and pepsin secretion was examined and acid and pepsin outputs were measured. After secretory tests, the rats were sacrificed, the stomachs removed and the damage to the gastric mucosa was assessed by measuring the lesion area planimetrically and by histology, the gene expression in gastric mucosa for HDC and interleukin-1β (IL-1β) was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot. Additionally, somatostatin concentration in gastric juice, gastric mucosal histamine content and plasma gastrin and IL-1β levels were determined using radioimmunoassay (RIA). Results: Administration of Hp-WE failed to induce gross mucosal damage but microscopic examination revealed partial denudation of gastric surface epithelium without causing deep necrosis. In secretory tests, Hp-WE produced marked hypochlorhydria but type I Hp-WE induced significantly stronger inhibition of acid and pepsin secretion than type II Hp-WE, both at days 7 and 14. Both, type I and type II Hp-WE suppressed significantly the gene expression for HDC mRNA and lowered significantly gastric mucosal histamine content as compared to respective values in vehicle-treated control gastric mucosa. Furthermore, Hp-WE, resulted in a significant increase in expression of IL-1β mRNA and a significant fall in luminal somatostatin concentration as well as a insignificant elevation of plasma gastrin level, the type I Hp-WE being more effective in these alterations than type II Hp-WE. Conclusions: (1) Ability of Hp-WE to induce superficial damage, the reduction in HDC mRNA and accompanying fall in gastric histamine release, contribute, at least in part, to marked hypochlorhydria observed in the stomach exposed to repeated Hp-WE treatments, and (2) the deleterious effect of Hp-WE on the gastric mucosa involves an impairment of gastrin-somatostatin link possibly resulting from the action of Hp-derived toxins and the induction in mucosal cells of proinflammatory cytokine such as IL-1β.

Mouse model of Helicobacter pylori infection: studies of gastric function and ulcer healing.

Helicobacter pylori infection in humans is a major risk factor for peptic ulcer, but studies on the relation between H. pylori infection and gastric pathology are limited due to a deficiency of convenient animal models resembling this infection in humans. We studied the effects of inoculation of conventional BALB/c mice with CagA and VacA positive (type I) H. pylori or CagA and VacA negative H. pylori (type II) strains on gastric secretion and healing of chronic acetic acid-induced ulcers in mouse stomachs. The ulcer area, gastric blood flow, plasma interleukin (IL)-1beta and IL-12, as well as plasma gastrin and gastric luminal somatostatin were determined. Gastric mucosal biopsy samples were also taken for assessment of the presence of viable H. pylori using a rapid urease test, H. pylori-culture and the RT-PCR analysis of the signal for H. pylori CagA. Gastric acid and pepsin secretion was reduced by over 50% immediately after H. pylori inoculation and accompanied by a significant increment in plasma gastrin and fall in gastric luminal somatostatin content observed over all test days, particularly in mice infected with type I H. pylori. The area of ulcers in vehicle-treated controls decreased significantly starting from day 2 after ulcer induction and then continued to decline for a further 14 days to heal almost completely after 28 days. In contrast, the ulcers were present until day 28 in all mice infected with type I or type II H. pylori strains, being significantly larger, especially with type I H. pylori infection. The gastric blood flow at the ulcer margin and ulcer crater in vehicle-treated mice gradually increased with decreasing ulcer size, after 14 and 28 days reaching a value which was not significantly different from that in vehicle-administered mice. In contrast, the gastric blood flow in type I H. pylori and, to a lesser extent, in type II H. pylori infected mice was significantly lower than in vehicle controls, both at the margin and at the crater of ulcers at all tested days. Histological changes such as oedema or congestion of surface epithelium were found after 7 days whereas mucosal inflammatory infiltration appeared after 14 days with a further increase after 28 days, especially in type I H. pylori and to a lesser extent in type II H. pylori infected mice. Plasma IL-1beta and IL-12 were significantly elevated at all tested days of ulcer healing and their increments were significantly higher in type I than in type II H. pylori infection. Conventional mice with gastric ulcers can be successfully infected by both toxigenic and nontoxigenic H. pylori strains, and this infection causes an immediate suppression of gastric secretion and markedly delays the healing of ulcers due to the fall in mucosal microcirculation in the ulcer region, cytokine release and an impairment in the gastrin-somatostatin link that appears to be independent of gastritis and more pronounced with infection of toxigenic than nontoxigenic strains.

Central nervous system action of melatonin on gastric acid and pepsin secretion in pylorus-ligated rats.

We recently demonstrated that centrally administered melatonin at low doses inhibits the induction of gastric lesions by water-immersion restraint stress. To investigate the mechanism of the potent anti-ulcer action of melatonin, the central nervous system (CNS) effects of melatonin on gastric acid and pepsin secretion were studied in conscious pylorus-ligated rats. Intracisternal (i.c.) melatonin (1-100 ng) dose-dependently decreased acid and pepsin output, while a higher i.p. dose (1 microg) had no inhibitory effect. The i.c. melatonin did not change serum gastrin concentrations. Serum melatonin concentrations at 1 and 4 h after i.c. administration of 10-100 ng melatonin did not differ from those in rats receiving i.c. vehicle. The present results suggest that melatonin administered centrally modulates the secretion of gastric acid and pepsin which may explain, at least in part, the protective, anti-stress role of melatonin in the gastric mucosa observed in our previous study.

Effect of Tityus serrulatus scorpion toxin on serum gastrin levels in anaesthetized rat

Scorpion toxin induces gastric secretion of acid and pepsin in rats. These effects seem to be mediated by the release of acetylcholine and histamine. However, the role of gastrin in the scorpion-toxin-induced gastric secretion is unknown. We describe the effects of the T 1 fraction purified from Tityus serrulatus scorpion venom on serum and on antral tissue gastrin levels in anaesthetized rats. Gastrin levels in serum and in the antral mucosa were measured before and at intervals 5, 15, 30, 60, 90 up to 120 min after the intravenous injection of saline or the T 1 fraction of scorpion venom (0.25 mg/kg) into anaesthetized rats. Antral G-cells were submitted to immunocytochemistry and electron microscopy. The data on gastrin were correlated with the gastric juice volume, and the acid and pepsin output increases induced by toxin. Scorpion toxin induced a significant increase in volume, acid output and pepsin output of gastric juice and gastrin serum levels 15–60 min after injection. Simultaneous measurements of antral gastrin levels did not show significant effects. The number of dense, intermediate and empty granules per μm 2 in the cytoplasm of antral G-cells was not significantly changed 60 min after saline or toxin injection. Scorpion toxin significantly increased serum gastrin; levels in rats.

Central nervous system action of melatonin on gastric acid and pepsin secretion in pylorus-ligated rats.

We recently demonstrated that centrally administered melatonin at low doses inhibits the induction of gastric lesions by water-immersion restraint stress. To investigate the mechanism of the potent anti-ulcer action of melatonin, the central nervous system (CNS) effects of melatonin on gastric acid and pepsin secretion were studied in conscious pylorus-ligated rats. Intracisternal (i.c.) melatonin (1-100 ng) dose-dependently decreased acid and pepsin output, while a higher i.p. dose (1 microg) had no inhibitory effect. The i.c. melatonin did not change serum gastrin concentrations. Serum melatonin concentrations at 1 and 4 h after i.c. administration of 10-100 ng melatonin did not differ from those in rats receiving i.c. vehicle. The present results suggest that melatonin administered centrally modulates the secretion of gastric acid and pepsin which may explain, at least in part, the protective, anti-stress role of melatonin in the gastric mucosa observed in our previous study.

Bacterial Lipopolysaccharide Protects Gastric Mucosa against Acute Injury in Rats by Activation of Genes for Cyclooxygenases and Endogenous Prostaglandins

Lipopolysaccharides (LPS) derived from gram-negative bacteria were reported to impair gastrointestinal mucosal integrity, but the results obtained are controversial. This study was undertaken to determine the effects of short-term administration of LPS on gastric secretion and gastric damage induced by 100% ethanol and to assess the role of the gene expression of two isoforms of cyclooxygenase (COX), constitutive (COX-1) and inducible (COX-2), and endogenous prostaglandins (PG) on these effects of LPS. Fasted rats received vehicle (control) or LPS (0.1–40 mg/kg i.g. or i.p.) without or with pretreatment with nonselective inhibitors of COX activity, indomethacin (5 mg/kg i.p.) and meloxicam (2 mg/kg i.g.), or the selective COX-2 inhibitor NS-398 (10 mg/kg i.g.), followed by intragastric application of 100% ethanol. The area of gastric lesions was determined by planimetry, gastric blood flow (GBF) was measured by the H₂-gas clearance technique, mucosal PGE₂ generation was measured by radioimmunoassay, and expression of COX-1 and COX-1 mRNA was determined by reverse transcription polymerase chain reaction (RT-PCR), quantitative RT-PCR with [³²P]dCTP and immunohistochemistry. LPS applied intraperitoneally in various doses (0.1–10 mg/kg), dose dependently inhibited gastric acid and pepsin secretion and significantly reduced the area of gastric lesions induced by ethanol, and this was accompanied by an attenuation of the ethanol-induced fall in GBF and increased mucosal generation of PGE₂. LPS applied in higher doses, such as 20 or 40 mg/kg, that caused systemic hypotension failed to protect the mucosa against 100% ethanol. Suppression of mucosal PGE₂ generation by indomethacin or meloxicam, significantly reduced the inhibitory action of LPS on gastric secretion and abolished LPS-induced gastroprotection and elevation of GBF. NS-398 did not influence PGE₂ generation, but significantly attenuated the protection and hyperemia induced by LPS suggesting that COX-2-derived products play an important role in gastroprotection. The expression of COX-1 mRNA, as determined by RT-PCR, quantitative RT-PCR and immunohistochemistry was found in intact gastric mucosa and after LPS administration. In contrast, the expression of COX-2 mRNA was undetectable in intact gastric mucosa but appeared in this mucosa 2, 4 and 8 h after LPS administration. COX-2 mRNA was not detected in rats treated with ethanol but, when LPS was applied before ethanol, the enhanced expression of COX-2 was detected without affecting COX-1 mRNA expression. We conclude that acute parenteral LPS affords gastroprotection against ethanol-damage through an increase in gastric microcirculation and overexpression of COX-2 and enhanced endogenous PG release.