Pepsin Concentration Research Articles

Ulcer perforation rate and pepsin. A study of the perfused cat esophagus.

The perforation rate of the cat esophagus varies as the log of the pepsin concentration when the esophagus is perfused in vivo with canine gastric juice at constant acidity, temperature, and pressure. The esophagus is extremely sensitive to gastric juice, frequently perforating before 60 minutes of perfusion. The maximal response is achieved with pepsin concentrations of 0.3 mg/mL, although the canine stomach is capable of concentrations as high as 1.3 mg/mL after vagal stimulation with 2 deoxy-D-glucose. These findings emphasize that peptic activity contributes significantly to initial acute esophageal ulceration induced by gastric secretions.

The differential enzyme sensitivity of rat immunoglobulin G subclasses to papain and pepsin

Monoclonal IgG belonging to the different rat IgG subclasses and IgG2a from normal rat serum were subjected to enzymatic degradation with papain and pepsin under several experimental conditions. IgG1 was found the most resistant to papain and IgG2a the most sensitive when the proteins were incubated in absence of cysteine or with low concentrations of the reducing agent (0.001 M). Papain digestion in the presence of 0.01 M cysteine led to the release of non-covalent Fc from rat IgG1, IgG2a and IgG2b. IgG1 and IgG2a were the most resistant to pepsin degradation, whereas IgG2c had very high sensitivity to the action of this enzyme. The effects of the increase of pepsin concentration and of the addition of cysteine were found to be different according to the IgG subclass. The pepsin Fc (pFc) fragment was generated in significant yields from rat IgG2a and IgG2c, but was absent from pepsin digests of IgG1. The mechanisms of resistance to proteolysis and its possible biological significance have been discussed.

Detection of immune deposits in glomeruli: A comparative study of paraffin-embedded, enzyme-treated sections and cryostat sections as substrates in immunofluorescence

Paraffin-embedded tissue can be used as substrate for immunohistochemistry after enzymatic treatment with proteases. The sensitivity of immunofluorescence on enzyme-treated paraffin sections and on unfixed cryostat sections is compared in this study. Pepsin was more efficient by weight than trypsin in restoring the antigenicity of immune deposits. Increased fluorescence intensity was obtained up to a pepsin concentration of 0.4%. Intensity was further increased when pepsin treated sections were treated with trypsin. Immune deposits were detected in enzyme treated, paraffin sections of kidneys of mice injected with anti-GBM diluted 1/200 or less and in cryostat sections of mice injected with anti-GBM diluted 1/400 or less. This small decrease in sensitivity is considered trivial compared with the advantage gained by the excellent preservation of the tissue.

Secretory kinetics of electrolytes in porcine gastric juice from Heidenhain pouch.

A Heidenhain pouch usable for several months was constructed in a Landrace secondary SPF piglet. The behaviors of electrolytes and pepsin in the gastric juice induced by tetragastrin (TG) were studied in the piglet, in comparison with the dog. A high positive correlation was observed between H+ concentration and secretory volume. The same results were obtained by stimulation with betazole and carbamylcholine. The concentrations of Na+ and Ca++ decreased, but those of K+ and Cl- increased with an increase in volume. The concentrations of these 4 ions correlated highly with H+ concentration or volume. Mg++ concentration increased temporarily after the TG administration and decreased there after. This curious responste of Mg++ concentration was observed in the dog, as well as in the piglet, after administration with any other stimulant. Pepsin concentration increased temporarily after TG stimulation, then turned to be at a basal level, and increased slightly thereafter. The kinetics of electrolytes on the gastric juice in the pig seemed to resemble that in the dog.

Cigarette smoking, chronic peptic ulceration, and pepsin 1 secretion.

The relationship between the secretion of pepsin 1 (the most electronegative of the pepsins), and the smoking habits of 219 patients has been investigated. Significantly more cigarette smokers with peptic ulceration (72.5%) secreted pepsin 1 in greater than trace amounts after pentagastrin or histamine than did non-smokers with ulceration (51.2%). Differences of a similar order were found for men with duodenal ulcer, women with duodenal ulcer, and all patients with gastric ulcer, but the difference was statistically significant only for men with duodenal ulcer. Significantly more patients with peptic ulcer smoking six to 15 cigarettes/day secreted moderate or high concentrations of pepsin 1 than did heavier smokers or non-smokers. There was no significant association between cigarette smoking and pepsin 1 secretion among 74 patients without ulceration. Maximal acid output was not significantly related to smoking in any group studied. The findings add to the increasing body of evidence linking pepsins and pepsin 1 with the pathogenesis of peptic ulceration.

Ulceration of Isolated Amphibian Gastric Mucosa

Protective mechanisms in gastric mucosa were investigated with the use of closed sacs and open sheets of isolated frog gastric mucosa. Closed sacs ulcerated at a high rate (80%) in a phosphate-buffered serosal medium devoid of HCO3- and gassed with 100% O2. In a nutrient solution buffered with CO2-HCO3-, the incidence of ulceration was significantly lower (10%). The protection afforded by HCO3- in the serosal solution was the same regardless of the presence or absence of CO2. Alkalinization of the serosal medium per se did not protect the mucosa, whereas buffering the luminal contents of the sacs to pH 7 completely abolished ulceration. Acetazolamide, and, to a lesser degree, SITS, increased the susceptibility of the sacs to ulceration. Open sheets of frog gastric mucosa exposed to an acidic mucosal solution (pH 2) gassed with N2 on the mucosal surface to simulate the hypoxic conditions prevailing inside the sacs showed significantly lesser decreases in PD and Isc when the serosal solution contained HCO3- than when phosphate buffer was used. Gross ulceration did not occur, however, unless the concentration of pepsin in the acidic mucosal solution was elevated to the level encountered within closed sacs. Ulceration could be induced in open sheets gassed on both sides with 100% O2 in the absence of nutrient HCO3- only upon the addition of luminal pepsin with a mucosal pH of 2.0. The data indicate that both luminal H+ and pepsin are needed for ulceration to occur in the present model. The presence of nutrient HCO3- significantly protects the mucosa, possibly by providing an intracellular buffer to neutralize the in fluxing luminal H+ and/or by maintaining a higher rate of alkali (HCO3-) secretion by the surface cells of the mucosa.

Role of gastric mucosal pepsin in the pathogenesis of acute stress ulceration

AbstractMeasurements of acid and pepsin in gastric juice and the pepsin concentration in the fundic mucosa were performed in 4 patients who underwent partial gastrectomy for bleeding from acute gastric mucosal erosions (“stress ulcers”) and in 30 patients who underwent partial gastrectomy for chronic gastric or duodenal ulcers. The most striking finding was a significantly higher level of fundic mucosal pepsin in the patients with acute gastric erosions than the chronic ulcer patients. This finding was associated with a significantly lower concentration of pepsin in gastric juice, a low level of acid secretion, and the expected high plasma level of corticosteroids associated with stress. As a result, the ratio of gastric mucosal pepsin to gastric juice pepsin was significantly higher in patients with acute gastric erosions than in those with chronic ulcers. It is possible that a rapid increase in endogenous corticosteroid levels induces an increase in intracellular pepsin in the fundic mucosa, and that this sequence of events plays a role in the pathogenesis of stress ulcer.

Kinetics of pepsin-initiated coagulation of κ-casein

The kinetics of pepsin initiated coagulation of κ-casein have been studied at pH 5.8. The primary and secondary phases of coagulation are shown to proceed simultaneously. The theory of enzymatically initiated clotting reactions proposed by Payens (Payens, T.A.J. (1976) Neth. Milk Diary J. 30, 55–59) has been applied to this clotting system and has been used to obtain rate constants for the secondary phase of coagulation. As expected, clotting rate constants for κ-casein increase with pepsin concentration. An activation energy of 30.6 kcal/mol has been obtained for the secondary phase of coagulation. Turbidity measurements are a convenient means for studying the secondary phase of coagulation but do not provide an unambiguous means for studying the primary phase of the reaction.

INTRAPANCREATIC REGULATION OF HORMONE SECRETION IN THE DOMESTIC FOWL, GALLUS DOMESTICUS

The intrapancreatic endocrine regulation of hormone secretion by the chicken pancreas was studied. Fasted adult male chickens were prepared surgically for the collection of 'gastric' juice and blood samples from the femoral artery. Avian hormone preparations of insulin, glucagon and pancreatic polypeptide (APP) were injected at doses of 50 μg hormone/ kg body wt. Immunoassays of insulin, glucagon and APP were carried out on plasma, as were analyses for glucose, uric acid and free fatty acids (FFA). Gastric juice was analysed for volume flow and total protein, free acid and pepsin concentrations. Injection of insulin decreased all gastric parameters markedly (in contrast to its effect in mammals) and also increased the concentrations of FFA, glucagon (a bimodal response) and uric acid. The increases in levels of FFA, glucagon and uric acid occurred as early as 2·5 min after injection and considerably before significant hypoglycaemia was induced (15–30 min). Injection of glucagon caused a modest decrease in the volume of gastric secretion, but had little other effect except for a small increase in the amount of pepsin released. At 2·5 min, glucagon gave rise to a significant increase in the levels of insulin and FFA in the plasma, and after 15 min the levels of glucose and uric acid had also increased. A progressive decrease in the concentration of APP in the plasma was observed, which was greatest after 15 min and was 28% below control values. In all respects, APP was a powerful avian gastric secretogogue, but had no effect on the concentrations of plasma glucose and insulin. Whereas APP decreased the concentration of FFA in the plasma immediately, the peptide increased both the total and pancreatic levels of immunoreactive glucagon by 50% within 2·5 min, and this increase was even greater at 15 min. Collectively, the results obtained indicate, on a temporal basis, that intrapancreatic regulation of endocrine secretion occurs in Aves and that the release phenomena produce an immediate response. Subsequent or secondary hormone release may occur in response to peripheral metabolic events, especially those requiring homeostatic corrective measures.

Inhibition of gastric secretion by intraduodenal hypertonic glucose in patients with duodenal ulcer

Intraduodenal instillation of hypertonic glucose significantly inhibited tetragastrin-induced gastric acid and pepsin outputs in man. The secretory volume of gastric juice was markedly decreased, whereas, acid concentration remained unchanged. Pepsin concentration, on the contrary, was reduced significantly. The degree of inhibition of pepsin output, therefore, was greater than that of acid output. No significant difference in the extent of inhibition of acid or pepsin output was observed between control subjects and patients with duodenal ulcer.

Effect of cimetidine on intrinsic factor and pepsin secretion in man

The effect of cimetidine on gastric acid, pepsin, and intrinsic factor secretion was assessed in normal male subjects. Cimetidine (300 mg) completely inhibited acid, pepsin, and intrinsic factor concentration and output stimulated by betazole. In contrast, basal output of pepsin and intrinsic factor was not inibited. We conclude that H2-receptor antagonists inhibit betazole stimulation of intrinsic factor output in addition to their well-know inhibition of acid secretion.

Effect of Somatostatin on Pentagastrin Stimulated Secretion by Isolated Canine Stomachs, Perfused <i>ex vivo</i> with Homologous Blood

The effect of somatostatin on pentagastrin-induced gastric secretion was assessed on 6 isolated canine stomachs perfused ex vivo with homologous blood. Hormones were given at a constant rate into the gastric arterial circulation. Somatostatin caused inhibition of the HCl concentration and output and reduced the secretion volume in all stomachs studied. The output but not the concentration of pepsin was also reduced.

The Effect of Somatostatin on Pentagastrin-stimulated Gastric Secretion and on Plasma Gastrin in Man

Three experiments were carried out in each of 6 healthy students on separate days, in a randomized order. Intravenous saline infusions were given for one hour basally in each experiment. During the second hour either pentagastrin, pentagastrin and somatostatin, or somatostatin alone were given. Gastric juice was collected continuously during all experiments. Somatostatin decreased the volume of gastric secretion and the concentrations of acid and pepsin, and output of acid, pepsin, and intrinsic factor (IF). The plasma gastrin concentration was not changed by somatostatin. A rebound effect was seen on pepsin and IF outputs after cessation of somatostatin, and on blood sugar concentration. The present study suggests that somatostatin acts on gastric secretion either directly or by mechanisms other than by inhibition of gastrin. The rebound of pepsin and IF indicates a release-inhibiting action on these substances similar to the effect of somatostatin on the release of some hormones.

Effect of pepsin on ionic permeability of canine esophageal mucosa

Recently we have demonstrated that a “mucosal barrier” to H + is present in the esophagus of dog and man and in the presence of bile this barrier becomes more permeable to H +. In this study we measured the effect of pepsin on ionic movement across the mucosa of distally occluded canine esophagus. The rate of H + ion loss was increased significantly ( P < 0.001) when two different concentrations of pepsin were added to three different concentrations of HCl. Pepsin disrupts the esophageal “mucosal barrier,” and this observation suggests that reflux esophagitis in cases of incompetent gastroesophageal sphincter may be due to increased permeability of the mucosa to H + induced by pepsin.

Acid and pepsin secretion of separated gastric pouches during perfusion of antral pouches with cholinergic stimulating and blocking agents and lignocaine.

1. Secretion of HCl and pepsin from abomasal fundic pouches was studied in sheep during perfusion of antral pouches with cholinergic blocking and stimulating agents and lignocaine. 2. Resting secretion was reduced to about 50% of control levels and secretory responses to feeding were largely or completely blocked during antral pouch perfusions with atropine (0-01-0-16%) and hexamethonium (1%). 3. Antral pouch perfusions with lignocaine (2%) reduced fundic pouch resting secretion to about 60% of control values but did not block secretory responses to feeding. 4. Perfusions of acetylcholine (0-1%) and carbachol (0-0037 and 0-005%) through antral pouches characteristically stimulated increases in the concentration of acid, outputs of acid and pepsin, but not concentration of pepsin. 5. The mechanisms involved in the release of gastrin in the sheep are discussed. 6. It is concluded that antral secretion of gastrin contributes both to the maintenance of resting secretion of acid and the secretory responses of fundic pouches of sheep when they eat freshly provided food.

Gastric Mucosal Blood Flow and Pepsin Secretion in Dogs — Stimulation by 13-Nle-Motilin

In response to graded doses of intravenous 13-norleucine-motilin (13-nle-motilin)--a synthetic analogue of motilin and biologically equivalent to the natural polypeptide-, gastric mucosal blood flow (GMBF) in canine vagally denervated fundic pouches was studied using the aminopyrine clearance technique. As 13-nle-motilin did not exert any detectable effect on gastric secretion of hydrogen ions, intraluminal instillation of 160 mM HCl was used to provide a pH gradient allowing aminopyrine to move into the pouch lumen. With increasing doses of 13-nle-motilin, GMBF increased to 148% of control values; pepsin secretion - due to augmented pepsin concentration - rose concomitantly. Enhanced pepsin secretion was not accompanied by an increase in cyclic 3',5'-adenosine monophosphate secretion.

The Early Effect of Trimipramine (Surmontil) on Gastric Secretion in Man

The early effect of the trycyclic and antidepressive compound trimipramine (Surmontil; Pharma Rhodia) was examined in 10 patients with dyspeptic complaints. The gastric secretion was examined twice for one hour before, and one hour after, intramuscular injection of 1 mg histalog per kg body weight. In random order trimipramine was given perorally as two 50 mg tablets 3 hours before one of the gastric secretion tests. A significant decrease was found in volume and acid output of basal secretion after the peroral dose of trimipramine. The concentration and output of acid as well as the concentration of pepsin were significantly altered. After stimulation with histalog a significant reduction was found for volume and acid output, whereas the output of pepsin was unchanged. The reduction of acid secretion and volume could be ascribed to an anticholinergic effect of the drug.

Effects of an Orally Administered Prostaglandin Analogue (16,16-Dimethyl Prostaglandin E2) on Human Gastric Secretion

The secretory response to 16, 16-dimethyl prostaglandin E2 (DMPG) administered orally in 4 different dosages and to placebo was evaluated in healthy volunteers over a 2-hr period. During stimulation of gastric secretion by histamine, DMPG at the highest dosage (1.5 mug per kg) reduced volume by 47% and acid output by 79%. Pepsin concentration was not affected. At the same dose, DMPG inhibited basal secretion by 54% and 99% for volume and acid output, respectively. There were no side effects secondary to DMPG administration, which indicates that this compound may be useful in treating peptic ulcer disease.

Effect of urogastrone in the Zollinger-Ellison syndrome.

The effects of human urogastrone (0-25 mug. per kg. per hour intravenously) in four male patients with proven Zollinger-Ellison syndrome (z.e.s.) and in four healthy control subjects have been studied. After urogastrone in z.e.s. patients gastric acid volume and concentration decreased and basal acid output was reduced by 50-82%; the concentrations of intrinsic factor and pepsin in gastric juice increased by 60-300%; and peak plasma-gastrin concentration increased by 127-164% of basal concentration. A significant negative correlation between increase in plasma-gastrin concentration and decrease in acid output was observed (r=-0-72, P less than 0-01). Ulcer pain was relieved 30-60 minutes after the beginning of urogastrone infusion. These results suggest that urogastrone can inhibit the endogenously stimulated acid hypersecretion in z.e.s.

Stimulation of human pepsin output by tropical hydrochloric acid.

Pepsin secretion is stimulated by the back-diffusion of acid across the mucosa of the vagally denervated canine pouch. If back-diffusion is enhanced by damage, pepsin secretion increases. The current study investigates whether this mechanism exists in man. The stomach of normal human volunteers were irrigated for 1 hour with either buffer of 0.01 N HCl, 1 hour with 0.2 N HCl, and a final hour with buffer or 0.01 N HCl. During the middle hour both the concentration and output of pepsin increased three- or fourfold. From these studies it appears that the human gastric mucosa contains a mechanism similar to the dog's which results in the stimulation of pepsin secretion when exposed to acid. This mechanism could be of etiologic significance in gastric ulcer disease, which has been shown to be associated with increased gastric-mucosal permeability.