Regulation of acid secretion and paracellular permeability by F-actin in the bullfrog, Rana catesbeiana

Many studies have implicated F-actin in the regulation of gastric acid secretion using cytochalasin D (CD) to disrupt apical actin filaments in oxyntic cells. However, it is known that CD also affects mucosal permeability by disrupting tight junction structure. Here we investigated the contribution of F-actin to mucosal permeability and acid secretion in the stomach using CD. Stomachs were mounted in Ussing chambers and acid secretion (stimulated or inhibited), transepithelial resistance (TER), mannitol flux, bicarbonate transport, and dual mannitol/sodium fluxes were determined with or without CD. H(+) back diffusion was predicted from its diffusion coefficient. Incubation with CD resulted in a significant reduction in stimulated acid secretion. TER was unchanged in stimulated tissues but significantly reduced in inhibited tissues. Mannitol flux, bicarbonate transport, and H(+)-back diffusion increased significantly with CD. However, the rates of bicarbonate and H(+) flux were not large enough to account for the inhibition of acid secretion. These findings demonstrate that actin filaments regulate paracellular permeability and play an essential role in the regulation of acid secretion in the stomach.     

促胰液素和胆囊收缩素族激素对豚鼠肝胆汁分泌的影响

用具备胃瘘和胆瘘的豚鼠于人工维持胆汁酸池恒定的条件下,观察促胰液素(SEC)和胆囊收缩素(CCK)族激素[包括雨蛙肽(CAE)、五肽胃泌素(G5)和内源性CCK]对肝胆汁分泌的影响及其相互作用。结果表明:静脉灌注SEC、CAE或肠内灌注左旋苯丙氨酸(L-PHE,促内源性CCK释放剂)后,胆汁流量、胆汁HCO~-_3和Cl~-排出量均显著增多,并呈剂量-效应关系,但静脉注射G5则无利胆效应。在恒速灌注SEC的背景下,CAE或CCK对胆汁HCO~-_3排出的效应分别大于它们单独给予时的效应(P<0.05或P<0.01)。这些激素对胆汁酸的排出量均无影响。上述结果表明,SEC,CAE和内源性CCK均有利胆作用,所刺激的肝胆汁属于不依赖胆汁酸部分。G5则无利胆效应。对胆汁中HCO~-_3的排出,SEC与CAE或内源性CCK间有相互加强作用。     

Effect of sodium bicarbonate on aspirin-induced damage and potential difference changes in human gastric mucosa

Two aspirin tablets in 100 ml fluid will produce microscopical damage to the human stomach. A study was performed to determine whether a small amount of sodium bicarbonate (equivalent to one-third of a teaspoonful of baking soda) could protect against this damage. Sequential gastric biopsy specimens were taken from 15 healthy subjects before, during, and after intragastric instillation of one of the following isotonic solutions: saline; sodium bicarbonate; 600 mg aspirin suspended in sodium bicarbonate; and aspirin suspended in saline. On a separate day the same solutions were instilled, but gastric transmucosal potential differences were monitored. Light microscopy and scanning electron microscopy of the biopsy specimens showed occasional mucous degranulation of mucosal surface cells, but no cell damage during instillation of sodium bicarbonate. Light microscopy studies 10 minutes after aspirin in saline showed damage in 20% of surface cells, with focal areas of cellular disruption and microscopic erosions, but only 3·4% of cells were damaged after aspirin in bicarbonate and there were no erosions. Electron microscopy showed a damaged honeycombed appearance of surface epithelium after aspirin in saline and a normal cobblestone appearance after aspirin in bicarbonate. Aspirin dissolved in bicarbonate failed to induce the usual fall in potential difference.These findings indicate that sodium bicarbonate in amounts equivalent to one-third of a teaspoonful of baking soda protects the gastric mucosa against aspirin-induced damage and prevents the usual fall in potential difference after aspirin.     

An explanation of gastric hypersecretion in the pylorus-ligated rat

The hypersecretion of gastric acid in the pylorus-ligated rat has been shown to be of vagal origin. The present series of experiments were performed to identify the stimulus. The pyloric sphincter was ligated in a series of Sprague Dawley rats. Along with pylorus ligation, various other surgical manipulations were performed. Intestinal obstruction by ligation approximately 20 cm aboral to the cecum reduced unstimulated gastric secretion in the pylorus-ligated rat. However, perfusion of the lower small intestine with bicarbonate (143 mEq/L) stimulated secretion. Perfusion with either saline or deoxycholic acid (20 mEq/L) did not alter secretion. This supports a role for bicarbonate in the hypersecretion of gastric acid in the pylorus-ligated rat. The reflex appears to involve the myenteric plexus, since section of the pylorus seemed to attenuate gastric secretion. Plasma from animals with pylorus ligation, either alone or with intestinal ligation, equally inhibited gastric secretion. This suggests that while some factor inhibiting gastric secretion may be present, it appears to be unrelated to pylorus ligation.     

The sodium and bicarbonate dependence of bile secretion in the guinea-pig

The effects of the total substitution of sodium by lithium, and of bicarbonate by a mixture of chloride and phosphate, on the flow and composition of bile was studied in the isolated perfused guinea-pig liver using a single-pass perfusion system. 60% of secretion was bicarbonate dependent and 80% specifically required the presence of sodium. The secretion of bicarbonate in bile against a concentration gradient was inhibited by the presence of lithium. In contrast to the results of similar studies in the rat, lithium is not an effective substitute for sodium in maintaining bile secretion.     

The effect of oleate on pancreatic and bile secretion in the conscious rat

The effects of sodium oleate infused into either the duodenum or the terminal ileum on bile and pancreatic secretion were examined in the conscious rat. Rats were prepared with cannulae draining pure bile and pancreatic juice separately, and with an ileal and two duodenal cannulae. A 40 mM taurocholate solution containing 7 mg/ml bovine trypsin was infused into the duodenum throughout the experiment to replace diverted bile-pancreatic juice to maintain the normal regulation of pancreatic secretion. The intraduodenal infusion of sodium oleate significantly increased pancreatic juice flow, protein, and bicarbonate outputs, whereas it did not affect bile secretion. Intravenous infusion of proglumide (300 mg/kg/hr) did not inhibit pancreatic secretion stimulated by intraduodenal infusion of sodium oleate. An intravenous infusion of atropine (100 micrograms/kg/hr) attenuated protein and fluid secretions but not that of bicarbonate in response to intraduodenal oleate. In contrast, the intraileal infusion of oleate had no effect on pancreatic secretion, whereas it decreased bile flow, bicarbonate, and bile salt outputs. In conclusion, sodium oleate introduced in the duodenum stimulates pancreatic secretion but oleate in the terminal ileum inhibits bile secretion.     

Effect of intraduodenal sodium bicarbonate in rat and rabbit exocrine pancreatic secretion.

The effect of intraduodenal sodium bicarbonate, 0.1 M, on exocrine pancreatic secretion and the release of two peptides, secretin and VIP, was studied in anesthetized rats and rabbits, two species largely used in the gastroenterology laboratories. In the rabbit, intraduodenal sodium bicarbonate perfusion had no effect either on exocrine pancreatic secretion or on portal plasma levels of secretin and VIP. By contrast, in the rat, intraduodenal sodium bicarbonate perfusion significantly increased hydroelectrolyte exocrine pancreatic secretion and portal plasma secretin levels. A clear interspecific difference reflecting the different gastrointestinal physiology of both species is observed.     

Effects of parathyroid hormone on exocrine pancreatic secretion in parathyroidectomized dogs

The effects of intravenous parathyroid hormone (PTH) on steady state Secretin-induced pancreatic secretion were studied in seven dogs before and after parathyroidectomy. Free flow of pancreatic juice was obtained by direct cannulation of the main pancreatic duct (the minor duct being ligated) : a gastric fistula prevented the entry of gastric acid into the duodenum. In the normal dog PTH caused a significant increase in volume and bicarbonate concentration, reciprocal change in chloride and no change in total protein concentration. The stimulatory effect of PTH was dose-dependent. In the parathyroidectomized dog, the basic Secretin-induced secretion was lower than the preoperative values, but PTH infusion caused a significant increase in volume of fluids and bicarbonate concentration, reciprocal change in chloride and no change in protein concentration. These results were not dependent on calcium blood level, and did not change after calcium injection to the hypocalcemic parathyroidectomized dog. It is suggested, that PTH may have a direct effect on pancreatic exocrine secretion.     

Effect of atropine on plasma gastrin and somatostatin concentrations during sham feeding in man

The purpose of these studies was to measure circulating gastrin and somatostatin concentrations during sham feeding in humans and to evaluate the effect of two doses of intravenous atropine on circulating concentrations of these peptides. Gastric acid and bicarbonate secretion and pulse rate were also measured. Sham feeding increased plasma gastrin concentrations by approximately 15 pg/ml but had no effect on plasma somatostatin-like immunoreactivity (SLI). A small dose of atropine (5 micrograms/kg) augmented plasma gastrin concentrations during sham feeding significantly (P less than 0.01), but did not affect plasma SLI. Atropine also significantly inhibited gastric acid secretion and gastric bicarbonate secretion (by 62% and 52%, respectively), but pulse rate was not affected. A larger dose of atropine (15 micrograms/kg intravenously) suppressed plasma gastrin concentrations significantly compared to the smaller 5 micrograms/kg atropine dose (P less than 0.02), so that plasma gastrin concentrations when 15 micrograms/kg atropine was given were not significantly different from those during the control study. 15 micrograms/kg atropine reduced gastric acid and bicarbonate secretion by 81% and 66%, respectively, and also increased pulse rate by 15 min-1. These studies indicate that small doses of atropine enhance vagally mediated gastrin release in humans, probably by blocking a cholinergic inhibitory pathway for gastrin release. Although the nature of this cholinergic inhibitory mechanism is unclear, we found no evidence to incriminate somatostatin. Our finding that the larger dose of atropine reduced serum gastrin concentrations compared with the smaller dose suggests that certain vagal-cholinergic pathways may facilitate gastrin release.     

Ion secretion by salt glands of desert iguanas (Dipsosaurus dorsalis)

Unlike the NaCl-secreting salt glands of many birds and reptiles, the nasal salt glands of lizards can secrete potassium as well as sodium, with either chloride or bicarbonate as the accompanying anion. The factors responsible for initiating secretion by the gland and the rates of cation and anion secretion were studied in the desert iguana, Dipsosaurus dorsalis. Lizards were given combinations of ions for several days, and secreted salt was collected daily and analyzed for sodium, potassium, chloride, and bicarbonate. Maximum total cation secretion rate was 4.4+/-0.38 micromol/g/d. Cation secretion ranged from 24% to 100% potassium; even high NaCl loads did not abolish potassium secretion. Maximum bicarbonate secretion was about 0.5 micromol/g/d; chloride was the predominant anion. Secretion rate increased only in response to those treatments that included potassium and/or chloride; sodium ions and other osmotic loads (e.g., sucrose) did not increase secretion. This is in contrast to birds and some other reptiles with salt glands, which initiate NaCl secretion in response to any osmotic load. The specificity of the response of the salt gland of Dipsosaurus may be related to the ecological importance of dietary potassium and chloride for herbivorous desert lizards.     

Neurotensin stimulates pancreatic exocrine secretion in rats

Neurotensin (NT) stimulates pancreatic exocrine secretion in dogs and humans. The purpose of this study was to examine the effect of exogenous neurotensin on pancreatic exocrine secretion in rats. Five Sprague-Dawley male rats were prepared with pancreatic, gastric and duodenal fistulas. Bile was shunted into the duodenum in order to collect pure pancreatic juice. 24 h later, neurotensin (0.05, 0.1, 0.2, 0.3, 1.0 nmol/kg) was infused intravenously in a random fashion. Pancreatic juice was collected every 10 min, and the volume was recorded and protein and bicarbonate were measured. Neurotensin stimulated, in a dose-related manner, the pancreatic secretion of water, protein and bicarbonate. Neurotensin may be involved in the physiologic control of pancreatic secretion in rats.     

Corticotropin-releasing factor inhibits gastric emptying in dogs: Studies on its mechanism of action

The effects of corticotropin-releasing factor (CRF) on gastric emptying of a saline solution was further investigated in six dogs prepared with gastric fistulas and chronic cerebroventricular guides and in four other dogs with chronic gastric fistulas and pancreatic (Herrera) cannulas. Intravenous infusion of CRF significantly inhibited gastric emptying whereas intracerebroventricular injection of CRF had no effect. Pharmacologic blockade of β-adrenergic system by propranolol did not modify intravenous CRF induced delay in gastric emptying. Intravenous CRF did not influence basal pancreatic secretion whereas secretin infused stimulated bicarbonate secretion. These results indicate that intravenous but not intracerebroventricular administration of CRF inhibited gastric emptying of a saline solution in dogs. The inhibitory effect of intravenous CRF on gastric emptying is not mediated by the β-adrenergic nervous system, and not secondary to the release of other peptides that affect both pancreatic secretion and gastric emptying such as cholecystokinin and peptide YY.     

Effect of histamine and cimetidine on amino acid meal-stimulated gastrin release at a controlled intragastric pH in healthy human beings

Results of several experiments have suggested that histamine-2 receptors play an inhibitory role in regulating gastrin release. We evaluated this prospectively in healthy human beings by infusing intravenously either histamine (0.33 μg/kg/min) or cimetidine (3.33 mg/min) during a continuous 3-h intragastric infusion of a 3% mixed amino acid meal, a potent stimulus of gastrin release. In order to be certain that effects of histamine or cimetidine on gastrin release were independent of their known effects on gastric acid secretion, intragastric pH was maintained at 5.0 by in vivo intragastric titration with sodium bicarbonate or hydrochloric acid. Although histamine and cimetidine had significant effects on gastric acid secretion, neither significantly affected the rises in serum gastrin concentrations during intragastric amino acid infusion. For example, mean gastrin rises above basal concentrations were 39 ± 9 pg/ml on the control day, 39 ± 9 pg/ml on the histamine day and 44 ± 11 pg/ml on the cimetidine day (P > 0.05). Thus, blockade or stimulation of H₂-receptors at the doses tested had no effect on gastrin release in response to an amino acid meal in humans when intragastric pH was maintained at 5.0.     

<Emphasis Type="Italic">In Vitro</Emphasis> Release Kinetics and Bioavailability of Gastroretentive Cinnarizine Hydrochloride Tablet

An oral sustained release dosage form of cinnarizine HCl (CNZ) based on gastric floating matrix tablets was studied. The release of CNZ from different floating matrix formulations containing four viscosity grades of hydroxypropyl methylcellulose, sodium alginate or polyethylene oxide, and gas-forming agent (sodium bicarbonate or calcium carbonate) was studied in simulated gastric fluid (pH 1.2). CNZ release data from the matrix tablets were analyzed kinetically using Higuchi, Peppas, Weibull, and Vergnaud models. From water uptake, matrix erosion studies, and drug release data, the overall release mechanism can be explained as a result of rapid hydration of polymer on the surface of the floating tablet and formation of a gel layer surrounding the matrix that controls water penetration into its center. On the basis of in vitro release data, batch HP1 (CNZ, HPMC-K100LV, SBC, LTS, and MgS) was subjected to bioavailability studies in rabbits and was compared with CNZ suspension. It was concluded that the greater bioavailability of HP1 was due to its longer retention in the gastric environment of the test animal. Batch no. HP1 of floating tablet in rabbits demonstrated that the floating tablet CNZ could be a 24-h sustained release formulation.     

吗啡和纳洛酮对酸化十二指肠引起狗胰液分泌的影响

本工作用制备 Thomas 胰瘘和胃痿的5条狗进行慢性实验。实验时用0.1N 盐酸灌入十二指肠以刺激胰液分泌,并分別注射吗啡或/和纳洛酮,观察它们对胰液分泌和对胰液中碳酸氢盐和蛋白质浓度的影响。另外我们还观察了吗啡和纳洛酮对6条狗离体胰主导管紧张性的影响。结果表明:(1)吗啡抑制了胰液分泌量,对胰液中碳酸氢盐和蛋白质浓度无影响,由于分泌量减少故两者的排出量显著减少(P<0.05),(2)纳洛酮本身对胰液分泌量和碳酸氢盐及蛋白质浓度均无影响;(3)纳洛酮可以加强吗啡抑制胰液分泌的作用(P<0.01);(4)吗啡能增加狗的离体胰主导管肌条的紧张性,纳洛酮不能阻断或翻转吗啡的这一效应,相反能加强其效应。本工作表明,吗啡抑制酸化十二指肠所引起的胰碳酸氢盐和蛋白质排出量,其机制可能是吗啡刺激胰导管收缩,而纳洛酮则加强吗啡的这种抑制效应。     

Pentagastrin-stimulated gastric acid secretion by the isolated perfused rat stomach

The purpose of this present study was to develop a method for stimulation of acid secretion by the isolated perfused rat stomach. Rat stomachs were perfused $\text{in}$$\text{situ}$ via the abdominal aorta and celiac axis with Krebs-Ringer bicarbonate buffer in the presence or absence of 10% ovine erythrocytes. The gastric lumen was perfused with distilled water and gastric contents were collected at frequent intervals through a catheter at the pylorus. Sixty minute gastric acid output in response to various concentrations of pentagastrin was determined by titration of gastric contents with 0.01 N NaOH to pH 7.0. During arterial perfusion with Krebs-Ringer bicarbonate buffer in the absence of ovine erythrocytes gastric acid output was 2.50±0.58 SEM μEq H⁺/h, which did not increase in response to perfusion with Krebs-Ringer bicarbonate buffer containing pentagastrin. However, inclusion of 10% ovine erythrocytes in the arterial perfusate resulted in substantial stimulation of gastric acid by pentagastrin: maximal acid output, achieved with a pentagastrin dose of 0.6 μg/kg/h, was 23.5±3.73 μEq H⁺/h (p<0.01). The results of the present study demonstrate the capacity of the isolated vascularly perfused rat stomach to secrete acid and provide a model for studying interactions of gastrointestinal regulatory peptides and their physiologic roles in the regulation of gastric acid secretion.     

Effect of somatostatin on exocrine pancreatic secretion stimulated by pancreozymin-secretin or by a test meal in the dog

In 4 dogs with chronic duodenal and gastric fistulae, exocrine pancreatic function was assessed by cannulating the pancreatic duct and collecting the duodenal contents. Both methods were applied in each animal. Pancreatic secretion was stimulated by infusion of 2 CHR units of pancreozymin and secretin or by administration of a liquid test meal, injected into the stomach through the gastric fistula. During both experiments 3.5 microgram/kg somatostatin was given as bolus injection followed by an infusion of 3.5 microgram/kg/h. Somatostatin caused a significant reduction in protein and amylase output and in the bicarbonate concentration during stimulation with pancreozymin-secretin. Volume and bicarbonate slightly decreased but not to a significant extent. Duodenal volume and the duodenal activities of trypsin and amylase were significantly reduced during test meal stimulation and somatostatin infusion. Somatostatin is a potent inhibitor of exocrine pancreatic function mainly influencing enzyme secretion.     

Evaluation of antifungal activity of carbonate and bicarbonate salts alone or in combination with biocontrol agents in control of citrus green mold

The aim of this research was to determine if the attacks of green mold on orange could be reduced by edible salts alone or in combination with biocontrol agent. For this purpose toxicity to Pantoea digitatum and practical use of sodium carbonate (SC), sodium bicarbonate (SBC) and potassium carbonate, and potassium bicarbonate alone or in combination with antagonistic bacteria (Pseudomonas fluorescens isolate PN, Bacillus subtilis isolate VHN, Pantoea agglomerans isolate CA) to control green mold were determined. All were fungistatic. SC and SBC were equal and superior to the other salts for control of green mold on oranges inoculated 6h before treatment and were chosen for subsequent trails under cold storage conditions. The biocontrol agents were found completely tolerant to 3% sodium bicarbonate and sodium carbonate at room temperature; although their culturability was reduced by > 1000-fold after 60 min in 1% other salt solutions. Satisfactory results were also obtained with the combined treatment for control of green mold. A significant increase in biocontrol activity of all isolate was observed when combined with sodium carbonate and sodium bicarbonate. The treatments comprising CA combined with SB was as effective as fungicide treatment. Thus, use of sodium bicarbonate treatment at 3% followed by the antagonist P. agglomerans CA could be an alternative to chemical fungicides for control of green mold on oranges.     

Functional activities of the colon of the desert gerbil (Gerbillus cheesmani)

The effects of starvation and undernourishment on the potential differences (pd in mV), basal short-circuit current (Isc in microA/cm(2)), resistance (R in omega) and glucose-dependent short-circuit current (Isc in microA/cm(2)) across stripped sheets of proximal, mid and distal colon of the gerbil (Gerbillus cheesmani) were investigated. The effects of replacing sodium chloride by lithium chloride, replacing chloride in Krebs buffer by gluconate and removing bicarbonate from bathing buffers were also investigated. Starvation (4 days, water ad lib) and undernourishment (50% control food intake for 21 days) had no significant changes on pd and R of the three regions of stripped colon. Starvation increased the basal Isc in the proximal and the mid-colon only while undernourishment increased the basal Isc of three regions of the colon. In addition, starvation and undernourishment increased the glucose-dependent Isc in the three regions. Replacing sodium chloride by lithium chloride caused a slight decrease in the basal Isc of proximal and mid colon taken from starved animals. In undernourished gerbils, although there was a slight decrease in basal Isc of proximal and mid colon the big decrease was observed in Isc of the distal colon. Replacing chloride by gluconate had no effect on the Isc of the different regions of colon taken from fed and starved animals but decreased the Isc of the three regions of undernourished animals. The absence of bicarbonate reduced the Isc of proximal and mid colon taken from starved gerbils and those of three regions taken from undernourished animals. The results of the present study suggest that the Isc of proximal and mid colon from starved gerbils could result from active sodium transport together with bicarbonate secretion while the Isc of the three regions taken from undernourished gerbils results from active sodium absorption together with both chloride and bicarbonate secretion.