Increase In Gastric Acid Secretion Research Articles

Review article: influence of Helicobacter pylori on gastro‐oesophageal reflux disease in Japan

There is circumstantial evidence that infection with Helicobacter pylori is relatively protective for the occurrence of gastro-oesophageal reflux disease (GERD). It has been suggested that the Japanese population are protected against reflux oesophagitis by their high prevalence of H. pylori associated gastritis. Such gastritis, when becoming chronic, can lead to gastric atrophy, thereby reducing the likelihood of GERD. If this hypothesis is correct, the effects of H. pylori induced gastritis may be an important factor determining the earlier lower prevalence of oesophagitis in Japan, where this infection is especially common. In support of this idea a reduced prevalence of H. pylori infection in Japan, as is now being observed in young Japanese adults, may be, at least in part, responsible for the upsurge in the number of cases of reflux disease in Japan. Concomitantly, H. pylori eradication therapy in patients with gastritis or peptic ulcer disease, which is associated with an increase in gastric acid secretion, may also be at least partly responsible for the increased prevalence of reflux oesophagitis in the Japanese population.

Gastrointestinal-projecting neurones in the dorsal motor nucleus of the vagus exhibit direct and viscerotopically organized sensitivity to orexin.

Orexin (hypocretin)-containing projections from lateral hypothalamus (LH) are thought to play an important role in the regulation of feeding behaviour and energy balance. In rodent studies, central administration of orexin peptides increases food intake, and orexin neurones in the LH are activated by hypoglycaemia during fasting. In addition, administration of orexins into the fourth ventricle or the dorsal motor nucleus of the vagus (DMV) has been shown to stimulate gastric acid secretion and motility, respectively, via vagal efferent pathways. In this study, whole-cell recordings were obtained from DMV neurones in rat brainstem slices to investigate the cellular mechanism(s) by which orexins produce their gastrostimulatory effects. To determine whether responsiveness to orexins might be differentially expressed among distinct populations of preganglionic vagal motor neurones, recordings were made from neurones whose projections to the gastrointestinal tract had been identified by retrograde labelling following apposition of the fluorescent tracer DiI to the gastric fundus, corpus or antrum/pylorus, the duodenum or caecum. Additionally, the responses of neurones to orexins were compared with those produced by oxytocin, which acts within the DMV to stimulate gastric acid secretion, but inhibits gastric motor function. Bath application of orexin-A or orexin-B (30-300 nM) produced a slow depolarization, accompanied by increased firing in 47 of 102 DMV neurones tested, including 70 % (30/43) of those that projected to the gastric fundus or corpus. In contrast, few DMV neurones that supplied the antrum/pylorus (3/13), duodenum (4/18) or caecum (1/13) were responsive to these peptides. The depolarizing responses were concentration dependent and persisted during synaptic isolation of neurones with TTX or Cd2+, indicating they resulted from activation of postsynaptic orexin receptors. They were also associated with a small increase in membrane resistance, and in voltage-clamp recordings orexin-A induced an inward current that reversed near the estimated equilibrium potential for K+, indicating the depolarization was due in large part to a reduction in K+ conductance. Orexins did not affect synaptically evoked excitation, but did reduce membrane excitability in a subset of gastric-projecting DMV neurones by enhancing GABA-mediated synaptic input. Lastly, although many DMV neurones responded to orexins and oxytocin with excitation, for the most part these peptides modulated excitability of distinct populations of gastric-projecting vagal motor neurones. These results indicate that orexins act preferentially within the DMV to directly excite vagal motor neurones that project to gastric fundus and corpus. In this way, release of endogenous orexins from descending hypothalamic projections into the DMV may mediate the increase in gastric acid secretion and motor activity associated with the cephalic phase of feeding.

Gene expression of ornithine decarboxylase, cyclooxygenase-2, and gastrin in atrophic gastric mucosa infected with Helicobacter pylori before and after eradication therapy.

H. pylori (Hp) -induced atrophic gastritis is a well-known risk factor for the development of gastric cancer. Whether Hp eradication can prevent or retard the progress of atrophy and metaplasia has been the topic of numerous studies but the subject remains controversial. Recently, the increased expression of ornithine decarboxylase (ODC), gastrin and cyclooxygenase (COX)-2 has been shown to be increased in premalignant lesions in gastric mucosa and to play an essential role in the malignant transformation. The aim of the study is to assess the effect of eradication therapy on atrophic gastritis and analyze the gene expression for ODC, COX-2 and gastrin in gastric mucosa after succesful eradication in patients with atrophic gastritis. Twenty patients with chronic atrophic gastritis including both corpus and antrum of the stomach were included in this study. Four antral mucosal biopsy specimens were obtained from antrum and four from corpus. The histopathologic evaluation of gastritis was based on Sydney classification of gastritis. All patients were Hp positive based on the [13C] urea breath test (UBT) and the presence of anti-Hp IgG and anti-CagA-antibodies detected by ELISA. The patients were then eradicated with triple therapy consiting of omeprazol (2 x 20 mg), amoxycillin (2 x 1 g) and clarithromycin (2 x 500 mg) for seven days and vitamin C 1 g/day for three months. In gastric mucosal samples obtained from the antrum and corpus before and after eradication, the mRNA expression for ODC, COX-2, and gastrin was assessed by reverse-transcription polymerase chain reaction (RT-PCR). In all patients the gastric secretory analysis was performed by measuring gastric acid output and serum gastrin levels. After triple therapy the successful eradication assessed by UBT was observed in 95% of patients. In 45% of patients the infection with CagA-positive Hp strain was observed. Three months after eradication a significant reduction in the gastric activity (neutrophilic infiltrate) and severity (mononuclear infiltrate) of gastritis was observed. The atrophy score improved in both antrum and corpus after eradication. The expression of COX-2 and ODC was significantly up-regulated in the gastric mucosa of patients with atrophic gastritis and significantly reduced after eradication therapy. In all successfully eradicated patients with atrophic gastritis a significant increase in gastric acid secretion and decrease in serum gastrin were observed. We conclude that: (1) Hp eradication leads to the decrease in ODC and COX-2 gene expression in the gastric mucosa, and this may be relevant for the prevention of the Hp-associated gastric carcinogenesis; and (2) gastric atrophy ameliorates upon successful Hp eradication therapy.

Topical application of benzalkonium chloride to the stomach serosa increases gastric emptying time, acid secretion, serum gastrin and size of the mucosa.

In the present study we evaluated the effects of gastric myenteric denervation using benzalkonium chloride (BAC) on the time for gastric emptying, as well as gastric secretion, and mucosal epithelial cell size and population in rats. Wistar rats were treated with topical serosal application of BAC to the stomach. Control animals received saline. Ninety days after surgery, gastric emptying time, gastric acid secretion and serum gastrin levels were studied. Next, the animals were sacrificed and the stomachs were removed, fixed in formalin and histologically processed for histomorphometry of the height, area and volume of the glandular portion, and volume and population of mucous, chief, parietal, G- and labelled cells. BAC animals showed a significant delay in gastric emptying and an increase in gastric acid secretion and serum gastrin levels. These animals also presented a significant reduction of myenteric neuron number, hypertrophy of parietal and chief cells, hyperplasia of G cells and an increase in the gastric mucosa area. The absence of the myenteric plexus seems to protect the stomach from the hyperplastic effects of hypergastrinemia. Gastric food stasis may act as a factor triggering morphological and functional alterations of the gastric epithelium. Although gastric food stasis is a common finding in medical practice, its physiopathological consequences are poorly understood and have not been frequently discussed in the literature.

Absorption of biologically active peptide hormones from the small intestine of rat.

Absorption of the 4, 10 and 34 amino acid forms of gastrin from the small intestine has been investigated in anaesthetized rats. The method of assessment of successful absorption of the hormone into the systemic circulation was when the amount of acid secreted by the stomach over consecutive 15-min periods was increased. When the natural hormones were infused into the ileum in a relatively high dose, there was no increase in gastric acid secretion, indicating that they had not been absorbed. Each of the forms of gastrin was conjugated at the free amino terminus to the carboxyl group of cholic acid. Subsequent infusion of the conjugated form of gastrin into the ileum, this time in relatively low doses, resulted in substantial and prolonged increases in gastric acid secretion, indicating that these hormones had been successfully absorbed. In addition, conjugation of the 10 and 34 amino acid forms of gastrin with cholic acid was shown to increase markedly the potency in evoking an increase in gastric acid secretion in response to intravenous injection of the hormone. Absorption of the gastrin conjugates was specific to the ileum thus indicating that they had been absorbed through the bile salt transporters.

Neuronal expression of Fos protein in the brain after intravenous injection of gastrin in rats

The present study examined whether the central neurons are involved in the stimulatory action of gastrin on the secretion of gastric acid. Gastrin (20 μg), which was examined and ascertained to induce a marked increase in gastric acid secretion in gastric-lumen perfused rats, was intravenously injected in Wistar rats under anesthesia with pentobarbital sodium. In the experiments, 1 h after injecting gastrin, rats were perfused and fixed, the brain was removed and sectioned at 40 μm thickness. Every fourth section was treated with anti-c-Fos antiserum, and c-Fos protein was immunohistochemically stained using the avidin–biotin complex method. It was found that c-Fos protein was expressed in neurons of the lateral habenular nucleus, the central nucleus amygdala, the lateral parabrachial nucleus in the pons, and the complex area of the nucleus of the solitary tract and the dorsal motor nucleus of the vagus nerve in the medulla oblongata. The control rats were injected with saline solution, and the brain sections were processed similarly as described above. c-Fos protein was expressed in few neurons in the nuclei above in the control rats. These results suggest that gastrin released into the circulation might stimulate central neurons which, in turn, may relate to the control mechanism for the secretion of gastric acid.

Increased gastric acid secretion after Helicobacter pylori eradication may be a factor for developing reflux oesophagitis.

The role of acid secretion in reflux oesophagitis which may develop after H. pylori eradication is not well known. To investigate the participation of altered gastric acid secretion and the presence of hiatal hernia in the development of reflux oesophagitis after eradication therapy for H. pylori. A total of 105 patients with H. pylori infection, but without reflux oesophagitis at the time of eradication therapy, were followed prospectively for 7 months after the clearance of this microorganism. Gastric acid secretion was assessed by endoscopic gastrin test, and the presence of hiatal hernia by endoscopy. Reflux oesophagitis developed in 11 out of 105 (10.5%) patients when examined at 7 months after the eradication therapy. The incidence was correlated significantly with the increase in gastric acid secretion after the eradication of H. pylori, and was significantly higher in the patients with hiatal hernia (20%) than in those without it (0%). Increased acid secretion after H. pylori eradication is an important risk factor of reflux oesophagitis, especially in patients with hiatal hernia.

Inhibition of gastric acid secretion by saiboku-to, an oriental herbal medicine, in rats.

Intraduodenal saiboku-to (250-1000 mg/kg) dose-dependently reduced gastric acid secretion and histamine output, without altering acetylcholine output in pylorus-ligated rats. Saiboku-to also inhibited subcutaneous bethanechol (1 mg/kg) and tetragastrin (0.3 mg/kg) -induced increases in gastric acid secretion in vagotomized pylorus-ligated rats; however, it did not inhibit subcutaneous histamine (20 mg/kg) -induced increase in acid secretion. These results, taken together, suggest a possibility that saiboku-to may inhibit histamine release. Thus, the effect of saiboku-to on histamine release was directly investigated by using anti-dinitrophenyl IgE-sensitized rat peritoneal mast cells. Antigen (dinitrophenyl)-induced histamine release from the mast cells was clearly dose-dependently inhibited by saiboku-to at concentrations of 0.1-1.0 mg/ml. These results suggest that the inhibited gastric acid secretion with saiboku-to is due to inhibited histamine release.

Vagus-mediated activation of mucosal mast cells in the stomach: Effect of ketotifen on gastric mucosal lesion formation and acid secretion induced by a high dose of intracisternal TRH analogue

TRH analogue, RX 77368, injected intracisternally (i.c.) at high dose (3 μg/rat) produces gastric mucosal lesion formation through vagal-dependent pathway. The gastric mucosal hyperemia induced by i.c. RX 77368 was shown to be mediated by muscarinic vagal efferent fibres and mast cells. Furthermore, electrical vagal stimulation was observed to induce gastric mucosal mast cell degranulation. The aim of the study was to assess the influence of ketotifen, a mast cell stabilizer, on RX 77368-induced gastric lesion formation and gastric acid secretion. RX 77368 (3 μg, i.c.) or vehicle (10 μL, i.c.) was delivered 240 min prior to the sacrifice of the animals. Ketotifen or vehicle (0.9% NaCl, 0.5 mL) was injected intraperitoneally (i.p.) at a dose of 10 mg.kg –1 30 min before RX 77368 injection. The extent of mucosal damage was planimetrically measured by a video image analyzer (ASK Ltd., Budapest) device. In the gastric acid secretion studies, the rats were pretreated with ketotifen (10 mg.kg –1, i.p.) or vehicle (0.9% NaCl, 0.5 mL, i.p.), 30 min later pylorus-ligation was performed and RX 77368 (3 μg, i.c.) or vehicle (0.9% NaCl, 10 μL, i.c.) was injected. The rats were killed 240 min after i.c. injection, and the gastric acid secretion was measured through the titration of gastric contents with 0.1 N NaOH to pH 7.0. RX 77368 (3 μg, i.c.) resulted in a gastric mucosal lesion formation involving 8.2% of the corpus mucosa ( n = 7). Ketotifen elicited an 85% inhibition on the development of mucosal lesions ( n = 7, P < 0.001) whereas ketotifen alone had no effect on the lesion formation in the mucosa ( n = 7). The RX 77368 induced increase of gastric acid secretion was not influenced by ketotifen pretreatment in 4-h pylorus-ligated animals. Central vagal activation induced mucosal lesion formation is mediated by the activation of mucosal mast cells in the stomach. Mast cell inhibition by ketotifen does not influence gastric acid secretion induced by i.c. TRH analogue in 4-h pylorus-ligated rats.

Stimulatory effect of dibutyryl cyclic GMP on acid secretion in mouse isolated stomach and on histamine release in gastric mucosal cells

We previously reported that endogenous nitric oxide (NO) is involved in the peripheral control of gastric acid secretion induced by some secretagogues, and that endogenous NO is involved in the acid secretion process via histamine release from histamine-containing cells. However, the stimulus-secretion coupling in the cells remains to be clarified. In the present study, we investigated the effect of dibutyryl cyclic GMP on gastric acid secretion in mouse isolated stomach and on histamine release in gastric mucosal cells, in comparison with those of dibutyryl cyclic AMP. Dibutyryl cyclic GMP (300 μM) produced a slight but significant increase of gastric acid secretion, which was completely inhibited by the histamine-H2 receptor antagonist famotidine. In contrast, dibutyryl cyclic GMP (1 mM) markedly inhibited histamine-induced acid secretion. Dibutyryl cyclic AMP (100 μM) produced a sustained increase of gastric acid secretion. The pretreatment with famotidine partially inhibited dibutyryl cyclic AMP-induced gastric acid secretion. Dibutyryl cyclic GMP and dibutyryl cyclic AMP significantly increased the histamine release from gastric mucosal cells. These results suggest that both intracellular cyclic GMP and cyclic AMP act as second messengers for histamine release in the histamine-containing cells, probably ECL cells. On the other hand, in gastric parietal cells, cyclic AMP has a stimulatory effect on gastric acid secretion, whereas cyclic GMP has an inhibitory effect.

Gastroprotective Effect of Histamine and Acid Secretion on Ammonia-Induced Gastric Lesions in Rats

Background: Previous studies have shown that ammonia produced by Helicobacter pylori urease or administrated intragastrically exhibits a toxic effect on the gastric mucosa. In the present study we investigated the influence of histamine and gastric acid secretion on ammonia (NH4OH)-induced gastric lesions. Methods: The gastric mucosa in rats was exposed to NH4OH (1.5 ml of 250 mM solution) under basal conditions, after administration of histamine (1 mg/kg), urea with urease, and ranitidine (40 mg/kg subcutaneously) given alone or in combination. We measured the area of gastric lesions, gastric blood flow (GBF), plasma gastrin concentration, DNA synthesis, gastric acid secretion and gastric luminal concentration of PGE2. Results: Application of NH4OH resulted in the formation of acute gastric lesions. This effect was accompanied by a fall in GBF, a rise in gastric pH, and a reduction in mucosal DNA synthesis. Administration of histamine 30 min prior to NH4OH reduced the area of gastric lesions. This was accompanied by an increase in GBF, DNA synthesis, and prostaglandin E2 (PGE2) production. Ranitidine given prior to NH4OH enhanced gastric mucosa damage, and reduced GBF and DNA synthesis. This effect was accompanied by a reduction in gastric acid secretion. Ranitidine given prior to histamine abolished gastric acid secretion and the protective effect of histamine against NH4OH-induced damage; these effects were accompanied by a decrease in GBF, DNA synthesis, and concentration of PGE2. Pretreatment with 2% urea with urease given prior to NH4OH reduced NH4OH lesions. This effect was associated with an increase in gastric acid secretion, gastric generation of PGE2, GBF, and DNA synthesis. Ranitidine given prior to urea with urease inhibited gastric acid secretion and the gastroprotective effect of urea-urease gastroprotection. Conclusions: Histamine and gastric secretion exhibit a protective effect against ammonia-induced gastric lesions. This effect appears to depend upon the stimulation of gastric acid secretion and PGE2 production, and the improvement of gastric microcirculation.

Imidazoline derivatives and agmatine induce histamine release from the rat stomach

Strips from rat glandular stomach were used to investigate whether the imidazoline derivatives clonidine, tolazoline and BDF 6143 (4-chloro-2(2-imidazolin-2-ylamino)-isoindoline) and the guanidine derivative agmatine are able to release histamine from histamine-storing cells. Histamine was detected and quantified by HPLC. Clonidine, tolazoline and agmatine concentration-dependently induced a release of histamine from the gastric strips, whereas BDF 6143 was ineffective. However, BDF 6143 abolished the release-inducing effect of clonidine and agmatine. It is concluded that imidazoline and guanidine derivatives can induce histamine release from histamine-storing cells in the stomach by a specific mechanism (possibly via imidazoline receptors) which in turn might lead to a relevant increase in gastric acid secretion.

Roles of endogenous prostaglandins and nitric oxide in gastroduodenal ulcerogenic responses induced in rats by hypothermic stress

We examined the roles of endogenous prostaglandins (PGs) and nitric oxide (NO) in the gastroduodenal ulcerogenic responses to hypothermic stress (28∼30 °C) in anesthetized rats. Lowering body temperature provoked damage in the gastroduodenal mucosa, with an increase of gastric acid secretion and motility. These responses were completely abolished by bilateral vagotomy or atropine, while 16,16-dimethyl PGE 2 decreased the mucosal ulcerogenic response with no effect on acid secretion. The non-selective COX inhibitors, indomethacin or aspirin, worsened these lesions with enhancement of gastric motility and no effect on acid secretion, while the selective COX-2 inhibitor NS-398 did not affect any of these responses. On the other hand, the non-selective NOS inhibitor L-NAME but not aminoguanidine (a relatively selective inhibitor of iNOS), significantly potentiated the acid secretory and mucosal ulcerogenic responses in the stomach but reduced the duodenal damage in response to hypothermia, the effects being antagonized by co-administration of L-arginine. Hypothermia itself decreased duodenal HCO 3 – secretion under both basal and mucosal acidification-stimulated conditions. Both indomethacin and aspirin further decreased the HCO 3 – response to the mucosal acidification, while L-NAME significantly increased the HCO 3 – secretion even under hypothermic conditions, similar to 16,16-dimethyl PGE 2. These results suggest that 1) hypothermic stress caused an increase of acid secretion and motility as well as a decrease of duodenal HCO 3 – secretion, resulting in damage in both the stomach and duodenum, 2) the COX-1 but not COX-2 inhibition worsened these lesions by enhancing gastric motility and further decreasing duodenal HCO 3 – response, 3) the cNOS but not iNOS inhibition worsened gastric lesions by increasing acid secretion but decreased duodenal damage by increasing HCO 3 – secretion. Thus, it is assumed that the gastroduodenal ulcerogenic and functional responses to hypothermic stress are modified by cNOS/NO as well as COX-1/PGs.

Abnormal clearance of exogenous acid and increased acid sensitivity of the proximal duodenum in dyspeptic patients

Background & Aims: Although acid is likely to play a role in the genesis of symptoms in dyspeptic patients, most studies have failed to show an increase in gastric acid secretion. The aim of this study was to investigate clearance of acid from the duodenum and its relationship with symptoms in patients with functional dyspepsia. Methods: Twelve patients and 10 healthy volunteers were studied using an assembly allowing recording of pressures and pH. Acid and saline were infused intraduodenally during phase II and postprandially. Sensations were scored before and 1 and 5 minutes after each infusion. Results: After acid infusion in the fasting period, a greater increase in acidity in the duodenal bulb ( P = 0.007) and fewer duodenal pressure waves ( P = 0.002) were observed in dyspeptic patients. No significant differences in the time with pH < 4 and duodenal motor activity were observed in the postprandial period. Acid infusion reproducibly increased the sensation of nausea in patients ( P < 0.001) but not in the controls. Saline infusion had no effect on upper gastrointestinal sensations. Conclusions: In fasting dyspeptic patients, clearance of exogenous acid from the duodenal bulb and duodenal motor activity are decreased. The duodenal bulb in dyspeptic patients is hypersensitive to acid infusion, which induces the nausea. GASTROENTEROLOGY 1999;116:515-520

Effect of restorative proctocolectomy on gastric acid secretion and serum gastrin levels: a prospective study.

The aim of the present study was to analyze gastric acid secretion after restorative proctocolectomy, because it has been shown that ileal resection or exclusion may increase gastric acid secretion. An increased output of gastric acids may decrease the intestinal passage time and contribute to looser stools. Eleven patients who had elective colectomy and ileoanal pouch because of ulcerative colitis were investigated. Eight patient were males. Eight S-pouches and three J-pouches were constructed. Gastric acid secretion (retention, basic, and stimulated) was studied, together with serum gastrin, pentagastrin, and pepsinogen, in patients before colectomy and after having had the pelvic pouch functioning for 12 months. A significant increase, compared with preoperative levels, in retention, basic, and stimulated gastric acid secretion was found after 12 months with the pouch functioning. Levels of serum gastrin, pentagastrin, and pepsinogen were unchanged. Restorative proctocolectomy leads to a significant increase in gastric acid secretion. These findings may be of importance with regard to intestinal passage time and consistency of the stools.

Increase of gastric acid secretion after H. pylori eradication caused the development of reflux esophagitis

Increase of gastric acid secretion after H. pylori eradication caused the development of reflux esophagitis

5-CT or DOI augments TRH analog-induced gastric acid secretion at the dorsal vagal complex.

Serotonin (5-HT) interacts with thyrotropin-releasing hormone (TRH) at the dorsal vagal complex (DVC) to augment TRH-induced stimulation of gastric acid secretion. To investigate the 5-HT receptor family involved in the augmentation response, prototypical 5-HT receptor-selective agonists (146 pmol) were coinjected with the TRH analog RX-77368 (RX; 12 pmol) into the rat DVC in a 30-nl volume. The DVC coordinates were 0.2 mm anterior, 0.2 mm right, 0.6 mm ventral with respect to the calamus scriptorius. Coinjection of RX with the 5-HT agonists 5-carboxyamidotryptamine (5-CT) or (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI; 5-HT2 agonist) produced a 183 or 103% increase in gastric acid output compared with the RX injection alone. In contrast, coinjection of 2-methyl-5-HT (5-HT3 agonist) with RX produced no effect on RX-induced increase in gastric acid secretion. Moreover, coinjection of SC-53116 (5-HT4 agonist) decreased the gastric acid output by 45% compared with the RX response itself. Examination of the RX/5-HT agonist coinjection response in more rostral regions of the DVC using the same doses (5-CT/RX or DOI/RX) revealed that only 5-CT was effective in producing the augmented response to TRH analog. The results suggest that activation of 5-CT- or DOI-sensitive receptors augments, and of 5-HT4 receptors inhibits, the gastric acid response to TRH analog injected into the DVC. Thus the integrated response to several serotonin receptor subtypes may mediate changes to the TRH response induced by 5-HT at the DVC.

Reversal of gastric somatostatin receptor inhibition by Helicobacter pylori lipopolysaccharide with ebrotidine and sulglycotide

1. 1. Among the consequences of H. pylori infection is an increase in gastric acid secretion due to the impairment in feedback inhibition by somatostatin. Here, we show that lipopolysaccharide from H. pylori inhibits the binding of somatostatin to gastric mucosal receptor, and that antiulcer agents, ebrotidine and sulglycotide, are capable of countering this effect. 2. 2. The somatostatin receptor was prepared from the solubilized gastric mucosal epithelial cell membranes by affinity chromatography on Affi-Gel-bound [D-Tryp 8]SRIF-14 and used in the binding assays for 125I-labeled somatostatin in the presence of H. pylori lipopolysaccharide and antiulcer agents. 3. 3. The assays revealed a dose-dependent inhibition in the receptor-somatostatin binding by the lipopolysaccharide which reached a maximum of 94.1%. The effect of H. pylori lipopolysaccharide was countered by ebrotidine and sulglycotide, which at their optimal doses produced 94.9% and 84% restoration in somatostatin-receptor binding, respectively. 4. 4. The results demonstrate that the antiulcer agents, ebrotidine and sulglycotide, possess the ability to counteract the H. pylori interference with somatostatin regulatory effect on gastric acid secretion.

Evidence for a significant role of gastrin in cysteamine-induced hypersecretion of gastric acid.

Cysteamine has been known to stimulate gastric acid secretion and to induce duodenal ulcers in rats. We investigated the role of gastrin in cysteamine-induced acid hypersecretion in the perfused rat stomach. Intravenous infusion of cysteamine (75 mg/kg/h) resulted in a significant increase in acid secretion, which was accompanied by a marked increase in the plasma gastrin concentration. The cysteamine-induced increase in gastric acid secretion was completely blocked by i.v. injection of anti-gastrin rabbit serum (500 microliters). In addition, i.v. infusion of a CCK-B/gastrin receptor antagonist (L-365,260) (1 mg/kg/h) also suppressed the cysteamine-induced increase in acid secretion. Atropine significantly, but only partially, inhibited the increase. The elevated plasma gastrin levels induced by cysteamine were unaffected by atropine and L-365,260. In conclusion, cysteamine-induced acid hypersecretion is mediated mainly by cysteamine-induced gastrin release and partially by cholinergic factors. Furthermore, gastrin release caused by cysteamine appears to be independent of cholinergic tone.

Neurogenic stimulation of gastric acid secretion by the Na +,K +-ATPase inhibitor ouabain in mouse isolated stomach

1. 1. We have previously found the stimulatory effect of ouabain on gastric acid secretion. In the present study, we further studied the ouabain-induced acid secretion in mouse isolated stomach. 2. 2. In the resting stomach preparation, ouabain produced a transient increase in basal acid secretion, which was followed by a fall to the level lower than the initial basal level. 3. 3. The ouabain-induced acid secretion was abolished by tetrodotoxin or atropine, and was partially inhibited by hexamethonium or famotidine. High K + solution potentiated the ouabain stimulation. 4. 4. Endogenous ouabain has been recently identified in plasma of humans, but the physiological roles of this compound have not yet been defined. The present study in mouse isolated stomach showed that ouabain induced a transient increase in gastric acid secretion through the release of endogenous acetyl-choline, and subsequently inhibited acid secretion. It therefore seems likely that endogenous ouabain modifies gastric acid secretion in physiological and pathological conditions.