Influence of amytal and menadione on high-energy phosphates and acid secretion in frog gastric mucosa

Measurement of ATP and creatine phosphate in isolated frog gastric mucosa showed that amytal depressed the level of both high-energy compounds and inhibited acid secretion. Addition of menadione restored the ATP level to control values and partially restored the creatine phosphate levels but did not support acid secretion. Menadione was found to support that portion of active chloride transport which is not associated with acid output. It is concluded that an amytal-sensitive reaction, presumably mitochondrial coupling site I, is required for acid secretion to occur and that ATP is not a sufficient source of energy for this secretory process.     

A lyophilized aqueous extract of<Emphasis Type="Italic"> Maytenus ilicifolia</Emphasis> leaves inhibits histamine-mediated acid secretion in isolated frog gastric mucosa

Lyophilized aqueous extract of Maytenus ilicifolia leaves (LAEMIL) is commonly used in Brazilian folk medicine in the treatment of dyspepsia as well as gastric ulcers. We have investigated the effect and the possible mechanism of action of the LAEMIL on acid secretion in isolated frog gastric mucosa incubated in an Ussing chamber. It was observed that LAEMIL (7–28 mg%) as well as cimetidine (125–4,000 M), a well-known histamine H₂ receptor antagonist, decreased basal acid secretion in a concentration-dependent manner. Similarly to cimetidine (190 M), LAEMIL (21 mg%) also inhibited gastric acid secretion induced by increasing concentrations of histamine (50–800 M). The EC₅₀ values for histamine alone and histamine in the presence of LAEMIL or cimetidine were 94.6 M (71.1–125.9 M), 244.9 M (209.4–286.4 M) and 142.2 M (23.6–855.0 M), respectively. LAEMIL, histamine and cimetidine were effective on acid secretion only when added to the serosal surface of the mucosa. Furthermore, simultaneous addition of LAEMIL and cimetidine at concentrations, per se, ineffective, caused a 16% reduction in the basal acid secretion [from 8.3±0.3 to 6.9±0.2 Eq g^–1 (15 min)^–1, n=4]. Although effects such as inhibition of histamine biosynthesis and/or histamine release can not be ruled out, our data suggest that LAEMIL, like cimetidine, reduces acid secretion in the isolated frog gastric mucosa by antagonising histamine H₂ receptors.Abbreviations LAEMIL Lyophilized aqueous extract of Maytenus ilicifolia leaves - Hist Histamine - Cim Cimetidine     

Role of glucose metabolism in acid formation by isolated gastric glands

The role played by glucose in providing energy for acid formation was studied in isolated gastric glands from rabbit. The widely-used inhibitors of glycolysis, iodoacetic acid and iodoacetamide were found to inhibit glucose oxidation as well as the indicators of acid formation, respiration and accumulation of aminopyrine. However, the potent inhibition of acid formation was found to involve a nonspecific mechanism other than the simple inhibition of glycolysis. An alternative approach involved use of the glucose transport inhibitor, phloretin. Phloretin blocked glucose oxidation and also inhibited functional responses. Acid formation was restored easily by the addition of pyruvate or various other oxidizable substrates. Measurement of lactate formation in the absence of exogenous glucose showed that the gastric glands contain very little glycogen. Addition of external glucose resulted in a 10-fold increase in lactate formation and this rate was stimulated further by histamine and rotenone. Rotenone also inhibited both respiration and aminopyrine accumulation; however, the inhibition was not complete. Phloretin treatment resulted in total inhibition of the residual aminopyrine accumulation after rotenone treatment. The results are interpreted to indicate that gastric glands are dependent almost totally on external substrate supply to support acid formation; and, that while anaerobic glucose metabolism can sustain a very low level of acid formation, the major role of glucose is to yield pyruvate equivalents for subsequent oxidation.     

Hypergastrinaemia induced by acid blockade evokes enterochromaffin-like (ECL) cell hyperplasia in chicken,hamster and guinea-pig stomach

Summary Treatment of chickens, hamsters and guinea-pigs with large doses of the long-acting antisecretory agent omeprazole for 10 weeks resulted in elevated serum gastrin levels and in increased stomach weight and mass of oxyntic mucosa. Also the antral gastrin cell density was increased. Another striking effect was the hyperplasia of the histamine-producing enterochromaffin-like (ECL) cells — a prominent endocrine cell population with unknown function — in the oxyntic mucosa. Accordingly, the gastric mucosal histamine concentration and rate of histamine formation were increased in all three species. The results suggest that marked and long-lasting suppression of acid secretion leads to elevated serum gastrin levels and diffuse ECL cell hyperplasia not only in the rat, as previously seen, but also in the chicken, hamster and guinea-pig; this hyperplasia is associated with accelerated histamine formation in all three species. The following sequence of events is suggested to occur in mammalian as well as submammalian vertebrates: suppression of acid secretion — hypergastrinaemia — ECL cell hyperplasia.     

Characterization of peptic inhibitory activity associated with sulfated glycoprotein isolated from gastric mucosa

Sulfated glycoproteins were extracted and purified from porcine stomach mucous scraping. Four sulfated glycoprotein fractions were separated and subsequently purified. These compounds always accompanied the apparent peptic inhibitory activity and consisted of 15–18% (w/w) protein. The carbohydrate portions contained an equimolar ratio of galactose and hexosamine (mainly glucosamine), together with lesser amounts of fucose and sialic acid. The sulfate content of the above fractions was 2–9% (w/w) of the total sulfated glycoprotein.The mode of inhibition of the sulfated glycoproteins to peptic activity was investigated and suggested that there was binding of the sulfated glycoproteins to the substrate of pepsin, making the substrate resistant to peptic activity. The sulfated glycoproteins neither bound pepsin at pH 1.8 nor inhibited the hydrolysis of a synthetic dipeptide substrate of pepsin. Desulfation of the sulfated glycoproteins resulted in the loss of both the inhibitory activity and the precipitate formation. The precipitation curve for sulfated glycoprotein and porcine serum albumin showed that both bound in varying proportions and suggests that both components are multivalent in this precipitate formation.     

Immunoreactivities for epidermal growth factor (EGF) and for EGF receptors in rats with gastric ulcers

Summary The present study was aimed at assessing whether epidermal growth factor (EGF) and its receptors are present in the gastric mucosa during the healing of gastric ulcers. Immunohistochemical, immunochemical and functional studies were performed in rats after induction of ulcers in the oxyntic mucosa. Controls, which included non-operated and sham-operated animals, displayed only rare cells in the bottom of the oxyntic glands showing EGF-like immunoreactivity. Within one day after ulcer induction, a markedly increased number of chief cells in undamaged mucosa showed intense staining. Concomitantly, there was an increased immunoreactivity for EGF receptors in the mucous neck cells. Maximal immunostaining for both compounds was observed at 3 days after ulcer induction; augmented staining was still demonstrable after 3 weeks. RIA revealed significantly increased EGF concentration in the oxyntic mucosa three days after ulcer induction, and at this stage stimulated gastric acid secretion, measured in a parallel group of chronic fistula rats, indicated significant inhibition. The transient increases in EGF-like and EGF receptor immunoreactivities may stimulate gland cell proliferation. The local release of EGF-like substances may also serve to reduce gastric acidity and thereby promote ulcer healing.     

Ultrastructural studies of endocrine-like cells in the fundic gastric mucosa of the bullfrog,Rana catesbeiana

Summary This study is concerned with electron-microscopic observations on endocrine or paracrine cells in the fundic gastric mucosa of the bullfrog. Also, an attempt was made to identify the histamine-releasing cells involved in the secretagogue response. At least three distinct endocrine-like cell types were found. The classification is based on the appearance of secretory granules and other organelles, and the relationship of endocrine-like cells with other cells in the tissue. The amphibian endocrine-like cells resemble the ECL, D and EC cells of mammals. Type-I (ECL) cells showed degranulation after repeated stimulation with tetragastrin (TG), acetylcholine (ACh) and K⁺ depolarizing solution, all of which release histamine.     

Structure-activity studies with cholecystokinin on gastric secretion in the cat

The influence of the position of the sulphate group in CCK on its gastric acid and pepsin stimulating activities was investigated in conscious cats with gastric fistulae. In Boc-CCK7, substitution of tyrosine-SO₃H by ε-hydroxynorleucine-SO₃H, an aliphatic amino acid approximating the length of tyrosine, enhanced acid secretory potency, whilst similar substitution by serine-SO₃H reduced potency, possibly due to the serine residue holding the sulphate group closer to the peptide backbone. Desulphation of Ser-CCK6 reduced acid secretory potency indicating that the known loss of potency upon desulphation of CCK-like peptides is not wholly dependent upon the presence of tyrosine residue in position 7. Sulphated CCK-like peptides are partial agonists of pepsin secretion, and desulphation confers full agonist activity. Analogues of CCK with serine or ε-hydroxynorleucine substituting for tyrosine, whether sulphated or not, showed full agonist activity in stimulating pepsin secretion. These data suggest the presence of the aromatic tyrosine residue, as well as sulphation, to be a necessary prerequisite for pepsin partial agonist activity in CCK-like peptides.     

Pharmacological analysis of wine-stimulated gastric acid secretion in dogs

Wine apparently stimulates gastric acid secretion both in man and animals, yet the underlying mechanism remains unclear. The present study was attempted to clarify the pharmacological properties involved in gastric acid secretion stimulated by wine in beagle dogs. Commercially available red or white wine, 14% ethanol, or 10% peptone meal was intragastrically administered to dogs with vagally denervated Heidenhain pouches. Gastric acid secretion was stimulated by both red and white wines (25-50 ml) for 45-60 min. While S-0509 only tended to inhibit wine-stimulated gastric acid secretion, both atropine and famotidine significantly inhibited wine-stimulated gastric acid secretion. Plasma gastrin level was not significantly increased by administration of red and white wines. Administration of 14% ethanol also stimulated gastric acid secretion, but the effect was about half of that of wine. Combined administration of wine and peptone resulted in a biphasic stimulation of gastric acid secretion. S-0509, atropine and famotidine significantly inhibited wine+peptone meal stimulation, yet the order of inhibition of cumulative acid secretion was in the order, famotidine>atropine>S-0509. It was concluded that wine stimulated gastric acid secretion in denervated dogs via acethylcholine- and histamine-dependent mechanisms, but nearly independent from the intervention of gastrin.     

Effects of luminal osmolarity on gastric acid secretion in the little skate,Raja erinacea

Summary Isolated gastric mucosa of the skate shows marked changes in acid secretory rate (J _H ), electrical potential difference (PD), and transepithelial resistance (R) with changes in mucosal bathing solution composition and a constant serosal solution. Removal of the 350 mM urea usually present in the mucosal solution reduces acid secretory rate by 25%, while adding urea to 1 M has no significant effect. Complete removal of osmotic solutes (distilled water) inhibits secretion by 78%, isotonic urea (no salts) inhibits by 54%, while isotonic salts alone (no urea) gives control secretory rates. The changes in PD and R are consistent with acid secretory changes. Theory and experience with terrestrial organisms would not predict these changes. The most likely explanation is osmotic swelling and shrinking of the surface cells, and occlusion of the secretory tubules in the swollen condition. Since marine species never encounter hypo- or hyperosmotic conditions due to food ingestion, their surface cells may be water permeable, unlike the situation in terrestrial and fresh water animals.Abbreviations J _H acid secretory rate per square centimetre tissue area - OC oxyntic cell - PBC pit border cell - PD transepithelial electrical potential difference - R transepithelial electrical resistance per square centimetre tissue area - SEC Surface epithelial cell     

Rapid mobilization of ferritin iron by ascorbate in the presence of oxygen

L-(—)-ascorbate mobilizes iron from horse-spleen ferritin in the presence of oxygen at pH 8.0. The reaction is strongly stimulated by Cu²⁺. Dehydroascorbate and other stable oxidation products of ascorbate are ineffective. We present evidence that monodehydroascorbate mobilizes ferritin iron by reduction.     

中西医结合治疗对幽门螺杆菌感染性胃溃疡患者胃黏膜的影响

目的 探讨中西医结合治疗对H. pylori感染性胃溃疡（Hp-GU）患者胃黏膜形态的影响及疗效。方法 选择2016年1月至2018年4月在我院内科治疗的Hp-GU患者74例,随机分为观察组与对照组各37例。两组患者均予以泮托拉唑肠溶片（40 mg/次,2次/d）、阿莫西林胶囊（1.0 g/次,2次/d）、左氧氟沙星片（0.2 g/次,2次/d）和枸橼酸铋钾胶囊（240 mg/次,2次/d）进行治疗,连用2周,2周后继续使用泮托拉唑肠溶片40 mg/次,1次/d,再用4周。观察组患者在此基础上加用半夏泻心汤加减治疗,连用6周。观察两组患者治疗前后胃黏膜形态的变化,并比较溃疡愈合情况、H. pylori清除率及患者不良反应。结果 治疗6周后,两组患者胃黏膜厚度、腺体密度及慢性炎症细胞浸润和活动性炎症细胞浸润评分较治疗前明显下降（P0.05）,观察组患者H. pylori清除率显著高于对照组（χ2=4.39,P<0.05）。结论 中西医结合治疗对Hp-GU患者的疗效确切,能显著改善患者胃黏膜形态,提高H. pylori清除率,且患者不良反应少,安全性较高。     

Exfoliation of gastric pit-parietal cells into the gastric lumen associated with a stimulation of isolated rat gastric mucosa in vitro: a morphological study by the application of cryotechniques

It is clinicopathologically important to elucidate the cell kinetics for the maintenance of normal gastric epithelium. In a rat gastric mucosa isolated after stimulation, a number of cells were exfoliated into the gastric lumen of the pit region. The present study was undertaken to clarify the origin of exfoliated cells and their histochemical profiles by taking the advantages of cryotechniques. As results, most of the exfoliated cells were identified as pit-parietal cells labeled with both peanut-lectin and anti-H+/K+-ATPase antibody. Quantitative analysis verified a time-dependent increase in the number of exfoliated cells in the gastric mucosa isolated after stimulation. The exfoliated cells exhibited a diffuse intracellular staining for E-cadherin, suggesting a dissociation of the adhesion molecule prior to the cell exfoliation. It should be noted that most of the exfoliated cells were negative to the apoptotic markers (TUNEL staining and caspase-3). Ultrastructurally, autophagosome-like structures consisting of H+/K+-ATPase positive membranes were frequently seen in the exfoliated pit-parietal cells. In addition, the pit-parietal cell exfoliation was accompanied by sealing of their basal portion with the cytoplasmic processes of adjacent surface mucous cells. The present morphological findings provide a new insight into the cell kinetics in the gastric epithelium in vitro.     

Co-localization of TFF2 with gland mucous cell mucin in gastric mucous cells and in extracellular mucous gel adherent to normal and damaged gastric mucosa

Trefoil factor 2 (TFF2) is mucin associated peptide that has a mucosal barrier function in addition to participating in repair and healing. We examined the localization of TFF2 and gastric mucins in gastric mucous cells, the surface mucous gel layer (SMGL) adherent to normal gastric mucosa, and in the mucoid cap covering gastric erosions. Carnoy’s solution, or formalin/picric acid-fixed paraffin embedded materials from resected stomachs and formalin-fixed paraffin embedded gastric biopsy materials were used. Sections were immunostained for the TFF2 and histochemically stained for gastric mucins. In addition, thick sectioned gastric mucosa fixed in Carnoy’s solution were stained with FITC-labeled GSA-II lectin specific for gland mucous cell mucin and examined for three-dimensional images of the SMGL using a confocal laser scanning microscope. The TFF2 and gland mucous cell mucin were found intermixed together in the gastric gland mucous cells, in the SMGL in laminated layers, and in the mucoid cap. A laminated arrangement of continuous sheets of gland mucous cell mucin in the SMGL was demonstrated in the three-dimensional images. Co-localization of the TFF2 with gland mucous cell mucin suggests a physical interaction between the TFF2 and gland mucous cell mucin. The TFF2 trapped in the adherent mucins may be responsible for mucosal defense, healing, and repair.     

Activity of oxyntomodulin on gastric acid secretion induced by histamine or a meal in the rat

Conscious rats with chronic gastric fistula were trained for drinking a 14-ml milk meal. The activity of an intestinal hormone, oxyntomodulin (OXM), was studied in this model and compared to that observed when histamine was the stimulus. Under histamine (0.25 mg·kg⁻¹·h⁻¹) stimulation, OXM at doses (60–120 pmol·kg⁻¹·h⁻¹) that induced physiological circulating levels inhibited gastric acid secretion up to 50%. Under meal stimulation, OXM reduced up to 29% acid secretion at doses (1–1.5 nmol·kg⁻¹·h⁻¹) inducing supraphysiological levels. We conclude that at physiological concentrations OXM cannot counteract the complex processes triggered by a meal. OXM would be a component of enterogastrone, a combination of several intestinal hormones acting in synergy. The OXM action is related to pathways recognizing the C-terminal 19–37 moiety of the molecule.     

Stimulatory effects of endogenous and exogenous nitric oxide on gastric acid secretion in anesthetized rats

We previously reported the stimulatory effect of endogenous nitric oxide (NO) on gastric acid secretion in the isolated mouse whole stomach and histamine release from gastric histamine-containing cells. In the present study, we investigated the effects of endogenous and exogenous NO on gastric acid secretion in urethane-anesthetized rats. Acid secretion was studied in gastric-cannulated rats stimulated with several secretagogues under urethane anesthesia. The acid secretory response to the muscarinic receptor agonist bethanechol (2 mg/kg, s.c.), the cholecystokinin(2) receptor agonist pentagastrin (20 microg/kg, s.c.) or the centrally acting secretagogue 2-deoxy-D-glucose (200 mg/kg, i.v.) was dose-dependently inhibited by the NO synthase inhibitor N(omega)-nitro-L-arginine (L-NNA, 10 or 50 mg/kg, i.v.). This inhibitory effect of L-NNA was reversed by a substrate of NO synthase, L-arginine (200 mg/kg, i.v.), but not by D-arginine. The histamine H(2) receptor antagonist famotidine (1 mg/kg, i.v.) completely inhibited the acid secretory response to bethanechol, pentagastrin or 2-deoxy-D-glucose, showing that all of these secretagogues induced gastric acid secretion mainly through histamine release from gastric enterochromaffin-like cells (ECL cells). On the other hand, histamine (10 mg/kg, s.c.)-induced gastric acid secretion was not inhibited by pretreatment with L-NNA. The NO donor sodium nitroprusside (0.3-3 mg/kg, i.v.) also dose-dependently induced an increase in acid secretion. The sodium nitroprusside-induced gastric acid secretion was significantly inhibited by famotidine or by the soluble guanylate cyclase inhibitor methylene blue (50 mg/kg, i.v.). These results suggest that NO is involved in the gastric acid secretion mediated by histamine release from gastric ECL cells.     

Ultrastructure and cytochemistry of the gastric mucosa of a reptile,Tiliqua scincoides

Summary The gastric mucosa of a reptile, the lizard Tiliqua scincoides, has been examined by light and electron microscopy. The gastric pits lead into glands that are extensively coiled in the proximal stomach but become progressively shorter and straighter in the distal stomach. The following epithelial cell types have been identified: (i) Surface mucous cells (SMC) line the entire lumenal surface as well as the pits. They contain mucus granules that stain with periodic acid-Schiff and, like the granules of mammalian SMC, commonly contain an electron dense core that appears not to be mucus (periodic acid-chromic acid-silver methenamine nonreactive). (ii) Glandular mucous cells are present in glands throughout the mucosa. They are probably homologous with the mucous neck and antral gland cells of mammals; like SMC their mucus granules contain nonglycoprotein cores. (iii) Oxynticopeptic cells (OPC) are the predominant cell type in the proximal glands but become infrequent distally. Their fine structure resembles that of OPC in other nonmammalian vertebrates, with features like those of both parietal cells and zymogen cells of mammals, (iv) Endocrine cells of three different types have been identified. Two of these show close similarities to the EC and ECL cells of mammals.The authors thank Mrs. D. Flavell for technical assistance. This study was supported by a grant from the Clive and Vera Ramaciotti Foundations