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At least 217 records · Page 12Linked to original sources

PubMed1983

Effects of eight weeks' continuous treatment with oral ranitidine and cimetidine on gastric acid secretion, pepsin secretion, and fasting serum gastrin.

Gastric acid secretion, pepsin secretion, and fasting serum gastrin levels were measured in 23 patients with duodenal ulcer disease, divided into three groups which received either cimetidine 800 mg daily, cimetidine 1600 mg daily, or ranitidine hydrochloride 300 mg daily for eight weeks. Pentagastrin tests were carried out at intervals both before and after treatment. Each dose of cimetidine reduced acid secretion to 42% of control one week after starting therapy. Ranitidine reduced acid secretion to 33% of the pretreatment value. Acid secretion remained suppressed to these levels throughout treatment with each drug. Acid secretion returned to pretreatment levels in all patients one week after treatment and remained normal until the end of the study. Both drugs reduced pepsin, which fell to 64% and 61% (p less than 0.01) after 800 mg and 1600 mg cimetidine respectively and to 65% (p less than 0.005) with ranitidine after one week's treatment. Pepsin secretion remained at this reduced level in both cimetidine groups till the end of treatment. Pepsin levels fell to 50% at two weeks of therapy with ranitidine but stabilised at this level till the end of therapy. Cimetidine withdrawal was followed by a return towards pretreatment levels of pepsin secretion; but secretion remained significantly depressed (p less than 0.05) to the end of the study period. In the ranitidine-treated patients pepsin output returned to normal after drug withdrawal. Fasting gastrin levels rose during treatment with both drugs but failed to reach significant levels. After withdrawal of treatment fasting serum gastrin levels returned to normal in all three groups of patients.

Anti-Ulcer Agents↗

PubMed1995

Pentagastrin increases pepsin secretion without increasing its fractional synthetic rate.

We studied the effects of increasing doses of pentagastrin on gastric secretion of pepsin and on incorporation of L-[1-13C]leucine into gastric aspirate protein as an index of pepsin synthesis. Pentagastrin (0.25-4.0 micrograms.kg-1.h-1) significantly increased pepsin output from basal 76 mg/h to < or = 181 mg/h but did not significantly alter incorporation of L-[1-13C]leucine from the basal fractional synthetic rate of 3.63 +/- 0.05%/h. In four subjects in whom infusion of tracer leucine was continued for > 1 day, aspiration of pepsin between 24 and 27 h demonstrated that plateau 13C labeling of leucine in pepsin had been attained, but at a value that was only 48% of the 13C labeling of plasma alpha-ketoisocaproic acid (alpha-KIC) [0.730 +/- 0.02 (SE) vs. 1.520 +/- 0.14 atoms %excess]. This suggests that actual rates of pepsin synthesis were approximately double those calculated on the basis of alpha-KIC labeling. The results are consistent with an interpretation that increasing doses of pentagastrin cause increased secretion of pepsinogen by recruitment of gastric chief cells, each synthesizing pepsinogen at an unaltered rate. Plateau 13C enrichment of alpha-KIC may not be a valid surrogate for plateau 13C leucine enrichment when fractional synthetic rates of some secreted proteins are calculated.

Adult↗

PubMed1991

Gastric acid and pepsin hypersecretion in conscious rabbits.

In conscious, gastric fistula rabbits, gastric acid and pepsin secretion averaged 4.5 +/- 0.1 mmol/h (1.3 mmol.kg-1.h-1) and 4.9 +/- 0.3 IU/h (1.6 IU.kg-1.h-1), respectively; these values represent approximately 40-50% of maximal output. Basal serum gastrin concentrations averaged 24 +/- 4 pg/ml and did not correlate with basal acid secretion. Atropine and vagotomy incompletely inhibited basal acid secretion (by 84 and 50%, respectively) and completely inhibited 2-deoxy-D-glucose-stimulated gastric acid secretion. Atropine and vagotomy similarly inhibited basal pepsin secretion by 50 and 40%, respectively. Ranitidine decreased acid and pepsin secretion, but as with atropine, inhibition was not complete (73 and 37%, respectively). Although omeprazole did not affect pepsin secretion, omeprazole completely inhibited basal acid secretion and elevated postprandial intragastric pH above 5.0. Conscious, gastric fistula rabbits have the highest basal acid and pepsin output among species commonly studied. Both vagal-cholinergic pathways and histamine drive basal acid and pepsin secretion in the rabbit.

Animals↗

PubMed1975

Relationship of thyrotropin to exophthalmos-producing substance: formation of an exophthalmos-producing factor by pepsin digestion of mouse pituitary tumor and human thyrotropin preparations.

The present report demonstrates that mouse tumor thyrotropin preprarations have exophthalmogenic activity. In addition it shows that the exophthalmogenic activity of mouse tumor thyrotropin can be increased by partial pepsin digestion, whereas the thyroid stimulating activity of mouse tumor thyrotropin is rapidly destroyed by such treatment. Thus, after 30 min of pepsin digestion, mouse tumor thyrotropin has 130% of its initial exophthalmogenic action but only 10% of its thyroid stimulating activity. Preparations of human thyrotropin are similarly sensitive to partial pepsin digestion, i.e., there is a rapid destruction of thyroid stimulating activity but a very much slower destruction of exophthalmogenic activity. Thus, after 30 min of pepsin digestion, preparations of human thyrotropin retain 80% of their exophthalmogenic activity but only 20-30% of their thyroid stimulating action. Since these results are analogous to those obtained in studies of the partial pepsin digestion of bovine thyrotropin (1), partial pepsin digestion of both purified human and purified mouse tumor thyrotropin preparations should yield an exophthalmogenic fragment of the TSH molecule devoid of thyroid stimulating action.

Animals↗

PubMed1997

Effects of sucralfate and its components on acid- and pepsin-induced damage to rat gastric epithelial cells.

We have established models of cell damage induced by acid and pepsin using rat gastric epithelial cells (RGM1). In the present study, the effects of aluminum hydroxide [Al(OH)3] and potassium sucrose octasulfate (KSOS), which are components of sucralfate, and sucralfate on cell damage and peptic activity of pepsin were examined. Pretreatment of cells with sucralfate (0.1-3 mg/ml) or Al(OH)3 (0.1-1 mg/ml) for 2 hr prevented both acid- (pH 4.0) and pepsin- (pH 4.5) induced cell damage. However, KSOS (0.1-1 mg/ml) did not show any effects on two different types of cell damage. The peptic activity of pepsin at pH 4.5 was about 10% of that at pH 2.0. Sucralfate and KSOS slightly inhibited peptic activity at pH 4.5. Al(OH)3 inhibited peptic activity by approximately 50%; however, no concentration-dependent pattern was observed. Pepstatin (0.003-0.1 mg/ml), a specific inhibitor of pepsin, inhibited the peptic activity in a concentration-dependent manner. Here, we confirmed that sucralfate and Al(OH)3 have cytoprotective effects against acid- and pepsin-induced cell damage. The mechanism behind the cytoprotective effects of sucralfate seems to relate to adhesion of the cell surface and neutralization of hydrogen ion by aluminum that prevents the penetration of hydrogen ions into the cells.

Acids↗

PubMed1996

Design and characterisation of long-R3-insulin-like growth factor-I muteins which show resistance to pepsin digestion.

Site-directed mutagenesis was used to construct pepsin-resistant, single-point mutations of the N-terminal extended IGF-I analogue, long-R3-IGF-I. In order to identify the most susceptible sites, the kinetics of long-R3-IGF-I digestion by purified porcine pepsin were determined. Pepsin initially cleaved the Leu10-Phe11 bond in the N-terminal extension peptide to generate FVN-R3-IGF-I, followed in rapid succession by cleavage at Gln15-Phe16, Tyr24-Phe25, Leu10-Val11 and Met59-Tyr60 in the IGF-I moiety. Single-point mutations at these sites were designed on the basis of the preferred cleavage bonds for pepsin, as well as amino acid substitutions less likely to disturb protein structure. These included Leu10Val, Phe16Ala, Phe25Leu, Asp53Glu and Met59Gln. All five muteins retained growth-promoting activity equivalent to or higher than that of IGF-I. In terms of pepsin susceptibility, Leu10Val and Asp53Glu were degraded as rapidly as the parent long-R3-IGF-I, Met59Gln and Phe25Leu were partially stabilised, and Phe16Ala showed a marked improvement in stability over a wide range of pepsin:substrate ratios. Accordingly, the Phe16Ala mutein, long-R3A16-IGF-I, has potential for oral applications to enhance gastric growth and repair.

Amino Acid Sequence↗

PubMedDate not supplied

Cholinergic and pentagastrin stimulation of the gastric secretions of acid, pepsin and lipase in the awake rabbit.

Acid, pepsin and lipase secretions were simultaneously studied in awake rabbits with a Heidenhain pouch during cholinergic (carbamylcholine 20 micrograms.kg-1 x h-1) or maximal pentagastrin stimulation (64 mu.kg-1 x h-1). To avoid lipase inactivation by low pH, the pouch was perfused at a constant pH, with a solution irrigating the pouch without inducing any pressure. Acid and pepsin outputs were equally activated by both stimulants. Lipase output was stimulated much more by pentagastrin (x26) than by carbamylcholine (x6). The maximal lipase output preceded that of acid output. Lipase concentration increased in the gastric juice whereas pepsin concentration remained constant. A negative correlation was calculated between acid and lipase or pepsin and lipase output. A positive correlation was obtained between acid and pepsin. Our data show that pepsin and lipase secretions which come from distinct chief cells, in the rabbit, responded to the same stimulants but with quantitative and timing differences.

Animals↗

PubMed1995

Susceptibility of beta-lactoglobulin and sodium caseinate to proteolysis by pepsin and trypsin.

The susceptibility of beta-LG and sodium caseinate to proteolysis by pepsin and trypsin was investigated using SDS or urea-PAGE. The effects were studied of heat, urea, and 2-mercaptoethanol on proteolysis. Native beta-LG was resistant to hydrolysis by pepsin or trypsin because of its compact globular structure. Heat treatment of beta-LG solutions at 90 to 100 degrees C for 5 or 10 min caused changes in the structure or conformation of the protein that rendered it accessible to pepsin and enhanced the extent of proteolysis by trypsin. The susceptibility of beta-LG to proteolysis by pepsin was markedly increased in the presence of urea (3 to 6 M), and the effect was reversible after removal of urea by dialysis. Proteolysis by trypsin was also increased by the presence of 2% 2-mercaptoethanol. Sodium caseinate was very accessible to pepsin without pretreatment and was extensively hydrolyzed at pH 1 to 5 in the presence of 5 M urea (which prevented the protein from precipitation in the isoelectric region); optimal pH was about 2. The activity of pepsin on sodium caseinate at pH 2 was not significantly affected by urea concentration up to about 8 M. The results indicated that the changes in conformation and structure of beta-LG that were induced by heating, reduction, or urea rendered the protein susceptible to peptic hydrolysis.

Animals↗

PubMed2001

Mucosal protective effects of ecabet sodium: pepsin inhibition and interaction with mucus.

Pepsin, acid and Helicobacter pylori are major factors in the pathophysiology of peptic ulcer disease and reflux oesophagitis. Ecabet sodium reduces the survival of H. pylori in the stomach and inhibits pepsin activity in the gastric juice of experimental animals. Here we have investigated the effects of ecabet sodium on some of the factors involved in the dynamics of the mucosal barrier, i.e. pepsins and mucins. This study used gastric juice obtained from 12 non-symptomatic volunteers and nine patients with reflux oesophagitis. Ecabet sodium significantly inhibited pepsin activity in human gastric juice, with a maximum inhibition of 78%. Pepsin 1, the ulcer-associated pepsin, was inhibited to the greatest extent. The ability of gastric juice to digest mucin was significantly inhibited by ecabet. As with gastric juice proteolytic activity, the inhibitory effect of ecabet on mucolysis was greater in gastric juice from patients with reflux oesophagitis than in that from controls. Ecabet sodium showed a positive interaction with gastric mucin, as assessed by an increase in viscosity. Thus ecabet sodium may reduce the aggressive potential of gastric juice towards the mucosa, which may be relevant in the treatment of reflux oesophagitis and peptic ulcer disease. In addition, it may strengthen the mucus barrier in peptic ulcer disease and gastritis.

Abietanes↗

PubMed1992

Role of mucus in mucosal protection through ethanol and pepsin damage models.

Gastrointestinal mucus is considered an important part of the mucosal defence mechanism against endogenous aggressors such as acid and pepsin. The mucus gel layer, adherent to the mucosal surface creates a diffusion barrier to luminal pepsin, thus protecting the underlying epithelium from the digestion by pepsin. The mucolytic pepsin will, however, digest the mucus at its luminal surface, but that lost is normally balanced by secretion of new mucus. This dynamic balance is disrupted when the mucus is exposed to excess pepsin, which causes focal haemorrhagic damage by progressively hydrolyzing the adherent mucus. The adherent mucus gel layer cannot contribute to the protection against exogen damaging agents such as ethanol and nonsteroidal anti-inflammatory drugs, as these compounds easily penetrate the mucus barrier causing, at high concentration, epithelial exfoliation. This study describes the basic properties and characteristics of gastric mucus and compares the pepsin-induced damage with the ethanol damage model.

Animals↗

PubMed1991

Hydrolysis of beta-casein by gastric proteases. I. Comparison of proteolytic action of bovine chymosin and pepsin A.

Hydrolysis of beta A2-casein by bovine chymosin and pepsin A was performed in order to compare the hydrolysis of the two enzymes on this protein. Different conditions have been tested: pH 5.5 for 116h and pH 3.5 for 7 h [E/S = 1/100 (w/w)] for chymosin. pH 3.0 for 24 h [E/S = 1/1000 (w/w)] for pepsin A. Under these conditions 17 peptides were obtained after the action of chymosin and 23 after the action of pepsin A. They corresponded respectively to the cleavage of 14 and 15 peptide bonds for chymosin and pepsin A. However, six of the peptide bonds were only hydrolyzed by chymosin and seven other bonds only by pepsin A. Our results showed a preferential splitting at the Leu-X, Ser-X, and Trp-X bonds for chymosin and Leu-X, Met-X, and Thr-X, for pepsin A. Some of the identified peptides contained sequences with possible physiological roles.

Amino Acid Sequence↗

PubMed1987

Pepsinogens, pepsins, and peptic ulcer.

The role of pepsin in the pathogenesis of peptic ulcer has been the subject of intense study and debate for many years. Two difficulties inherent in distinguishing between the role of acid alone vs acid and pepsin are that a) acid-containing gastric juice always contains pepsin, and, b) that hydrogen ion concentration (pH) is a major determinant of the activity of pepsin. However, studies in animal models of peptic ulcer indicate clearly that pepsin, in combination with acid, produces much more severe and more extensive mucosal damage than acid alone. Recent interest in pepsin and its precursor, pepsinogen, has stemmed from the finding that each is remarkably heterogeneous, and that the heterogeneity has a genetic basis. Results of studies using radioimmunoassays specific for the 2 major forms of pepsinogen, pepsinogen I and pepsinogen II, have shown that serum levels of pepsinogen I and pepsinogen II, and the ratio of pepsinogen I to pepsinogen II, can be used as noninvasive probes of gastric mucosal structure and function, indicators of the genetics and heterogeneity of duodenal ulcer, and as markers of increased risk for duodenal ulcer and gastric ulcer.

Duodenal Ulcer↗

PubMed1985

Taurodeoxycholate modulates the effects of pepsin and trypsin in experimental esophagitis.

Pepsin and trypsin cause erosive, hemorrhagic lesions in our rabbit model of experimental esophagitis. Since the gastroduodenal contents of patients with reflux esophagitis may also contain bile salts, we used our model to determine the effect that a bile salt, taurodeoxycholate (TDC), would have on the esophageal mucosa when combined with either pepsin in an acid perfusate (pH 2) or trypsin in an alkaline perfusate (pH 7.5). Indexes of esophageal injury included gross appearance of the mucosa, microscopic examination, and mucosal barrier integrity as determined by permeability to hydrogen ion. We found that when 5 mM TDC was combined with pepsin (0.3 mg/ml), the gross and microscopic changes of esophagitis, as well as net hydrogen ion flux, were diminished when compared with those observed with pepsin exposure alone. When increasing concentrations of TDC (2 to 10 mM) were added to pepsin, the morphologic degree of injury as well as hydrogen ion flux decreased in a dose-dependent manner. In contrast, when 5 mM TDC was combined with trypsin (1000 U/ml) in the alkaline perfusate, the gross and microscopic changes of esophagitis and the net of hydrogen ion flux were increased when compared with either bile salt or trypsin alone. These effects were also dose dependent. These data demonstrate that bile salts present in the gastroduodenal contents of patients with reflux esophagitis have the capacity to modulate the effects of pepsin and trypsin on the esophageal mucosa.

Animals↗

PubMed1983

[Pepsin-like enzyme of the macrophages and the immune system].

Pepsin enhanced phagocytosis of heterologous red blood cells by macrophages, but suppressed phagocytosis of homologous red blood cells. Antigen-presenting ability of the macrophages pulsed with heterologous red blood cells was augmented by pepsin, but not those pulsed with homologous red blood cells. On the other hand, an acid protease was found in macrophages that had biochemical and immunochemical properties which were quite close to those of pepsin. Along with phagocytosis of heterologous red blood cells by macrophages, the activity of this pepsin-like enzyme in macrophages showed an increase and extracellular release was also observed. Such changes were not observed in the macrophages that phagocytized homologous red blood cells or non-antigenic materials. Inhibition of this enzyme activity by pepstatin resulted in suppression of the phagocytosis of heterologous red blood cells. These results indicate that pepsin modulates macrophages functions and that a pepsin-like enzyme in macrophages plays an important role in the facilitation of phagocytosis and antigen-presentation by macrophages.

Animals↗

PubMed1981

Gastric pepsin and acid secretion in patients with acute and healed duodenal ulcer.

The relationship between gastric pepsin, acid secretion, and duodenal ulcer activity was studied in 33 patients with an endoscopically proven carter, in 17 patients who were studied within 3 mo of an acute crater but who no longer had a crater endoscopically, and in 10 patients who had no duodenal ulcer symptoms for longer than 3 mo after a crater and who had negative endoscopy. There were an additional 11 patients who had paired studies in the early-healed and late-healed stages of their disease. There were no significant differences between the values obtained in the paired and nonpaired group. Basal and pentagastrin-stimulated outputs of both pepsin and acid were significantly higher (p less than 0.001) when an acute crater was present than in 23 control subjects. At 3 mo or more after healing there was a significant (p less than 0.001) fall in both basal and stimulated pepsin and acid output which became insignificantly different from that of controls. In 104 basal studies the ratio of pepsin to acid secretion was 33,000 +/- 2500 (mean +/- SE) pepsin units/mmol H+ with no difference between any groups including controls. In 102 stimulated studies the ratio was 13,600 +/- 400 PU/mmol H+, also with no differences between any groups. Although data in the literature are conflicting, these results support a direct relationship between the activity of duodenal ulcer disease and acid-pepsin secretion.

Acute Disease↗

PubMed1981

[Direct action of timepidium bromide on the gastric mucosa and its inhibitory effect on pepsin secretion (author's transl)].

As quaternary ammonium compounds are generally not absorbed from gastric mucosa, the direct action of these compounds on the gastric mucosa can be investigated by means of intragastric (oral) administration to pylorus ligated animals. Effects of timepidium bromide (TB), an anti-cholinergic quaternary ammonium compound, on gastric secretion of pylorus ligated rats were investigated. When TB (100 mg/Kg) was administered orally, the secretion volume of gastric juice decreased slightly, while the concentrations of free acid and pepsin in gastric juice decreased remarkably. When TB was administered intraduodenally (100 mg/kg) or subcutaneously (10 mg/kg), secretion of gastric juice and free acid was strongly inhibited, but the pepsin concentration in gastric juice was not influenced (i.d.) or slightly increased (s.c.). In the oral administration of various drugs such as atropine, hyoscine-N-butylbromide and oxethazaine (Ox), only Ox caused a decrease in pepsin concentration in gastric juice. Similar effects of TB on the pepsin concentration in the gastric juice were also observed in experiments using stomach perfused rats. TB has no effect on enzymatic activity of pepsin in in vitro experiments. From these results, it is assumed that TB inhibits acid and pepsin secretion mainly by a direct action on the gastric mucosa.

Animals↗

PubMed1977

Pepsin immobilized on inorganic supports for the continuous coagulation of skim milk.

The milk-clotting enzyme pepsin was immobilized onto beads of alumina, titania, glass, stainless steel, iron oxide, and Teflon for treating skim milk in a fluidized-bed reactor. Two covalent attachment procedures using silanized supports and glutaraldehyde and two adsorption procedures were evaluated. The three best catalysts were titania and glass, using the covalent attachment procedure, and alumina, using the adsorption procedure at pH 1.2. The pepsin adsorbed on alumina catalyst has commercial potential compared to the previously used glass catalyst. Attempts to increase the stability of pepsin adsorbed on alumina by cross-linking with glutaraldehyde were unsuccessful owing to the low pH necessary for optimum pepsin adsorption; Desorption of pepsin from alumina during reactor operation was determined. Regeneration of spent catalysts was only partially successful.

Alum Compounds↗

PubMed1995

Purification and characterization of porcine pepsinogen B and pepsin B.

Porcine pepsinogen B was prepared from extracts of adult porcine fundic mucosa. Immunoelectrophoresis showed no immunochemical cross-reactions between pepsinogen B and other porcine gastric zymogens. Pepsin B was purified after activation of the zymogen. The enzyme showed an optimum of general proteolytic activity at pH 3.0. Activation of pepsinogen B at pH 2 resulted in formation of the covalent intermediate (pseudo-pepsin B) by proteolytic cleavage of bond Met16p-Glu17p (pig pepsinogen A numbering, "p" indicates residues of the prosegment peptide). Pseudopepsin B was stable at pH 2. The intermediate was converted to pepsin B at pH 5.5. The overall activation of pepsinogen B was much slower than found for other investigated gastric zymogens. During the conversion of pepsinogen B to mature pepsin B a segment of 43 amino acid residues was cleaved from the N-terminal of pepsinogen B. The amino acid sequence of the prosegment and the first 24 residues of pepsin B was determined. Relative to porcine pepsinogen A, progastricsin, and prochymosin, the following degrees of identities were observed: 40, 55, and 51%.

Amino Acid Sequence↗