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PubMed1973

The purification and properties of a single chicken pepsinogen fraction and the pepsin derived from it.

1. Evidence is given for the presence of at least five pepsinogens in a crude extract of mixed chicken stomachs. One of these was purified and could be activated to yield a single pepsin. 2. The molecular weights of the pepsinogen and pepsin were 36000 and 34000 respectively. The pepsin associated at low pH values and low ionic strength. 3. The amino acid analyses of both proteins are given. The pepsin was devoid of phosphate but contained carbohydrate. 4. The N-terminal amino acids of pepsinogen and pepsin were serine and threonine respectively. Five amino acids were released by carboxypeptidase A and it was deduced that serine may be the C-terminal one. 5. Each protein contained one thiol group per molecule as determined by titration with p-chloromercuribenzoate. The rate of the reaction was very rapid with pepsin, but much slower with pepsinogen, although the same group appeared to react in both instances. The enzymic activity of pepsin was unaffected by the modification. 6. The isoionic point of the pepsin was close to pH4.0 and the enzyme was stable for long periods at pH values up to 7.0. 7. The enzyme hydrolysed bisphenyl sulphite almost as rapidly as did pig pepsin A.

Amino Acids↗

PubMed1979

The specificity of some pig and human pepsins towards synthetic peptide substrates.

1. The peptidase activities of pig pepsins A and C and human pepsin and gastricsin were compared. 2. The peptides studied had the general formula A Leu Val-His-B. Hydrolysis at 37 degrees C and pH 2.07 occurred at the amino side of the leucine residue for all the enzymes and all the peptides. 3. When A was Ac-Ala the peptides were hydrolysed under these conditions slowly by pig pepsin C only. 4. Pig pepsin A and human pepsin were unable to hydrolyse the tyrosine-containing peptides under the conditions tested. Gastricsin (human pepsin C) had about one-third of the activity of pig pepsin C with these substrates. 5. The increase in the rate of hydrolysis caused by the extension of the chain by a single alanine residue was most marked for pig pepsin A and human pepsin.

Animals↗

PubMed1980

Purification and characterization of pepsinogens and a unique pepsin from rat stomach.

Four pepsinogens (1, 2, 3 and 4) (zymogens of pepsin A, EC 3.4.23.1, or pepsin C, EC 3.4.23.3) were purified from the fundic mucosa of rat stomach to homogeneous states as judged by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and a unique pepsin was purified from pepsinogen 1. The molecular weights of pepsinogens 1, 2, 3 and 4 were 42 000, 40 000, 40 500 and 39 000, respectively, and those of the respective activated pepsins (1, 2, 3 and 4) were 35 500, 40 000, 35 500 and 37 000, respectively, as estimated by polyacrylamide gel electrophoresis. The amino acid compositions of these four zymogens differed, but resembled those of pepsinogen Cs from various animal species. Rabbit antiserum prepared against pepsinogen 1 reacted with pepsinogen 2, but not with pepsinogens 3 or 4. The precipitin line against pepsinogen 1 fused completely with that against pepsinogen 2. Purified pepsin 1 was a unique pepsin showing remarkable stability in alkali. It resembled pepsin A with respect to inhibition by pepstatin and pepsin C with respect to its amino acid composition, but had properties intermediate between those of pepsin A and C with respect to its optimal pH (2.1 to 3.1) with hemoglobin and activity on N-acetyl-L-phenylalanyl-L-diiodotyrosine.

Amino Acids↗

PubMed2006

Neural and hydroxyl radical mechanisms underlying laryngeal airway hyperreactivity induced by laryngeal acid-pepsin insult in anesthetized rats.

Laryngopharyngeal or gastroesophageal reflux is associated with laryngeal airway hyperreactivity (LAH), but neither the cause-effect relationship nor the underlying mechanism has been elucidated. Here we established a rat model with enhanced laryngeal reflex reactivity induced by laryngeal acid-pepsin insult and investigated the neural and hydroxyl radical (*OH) mechanisms involved. The laryngeal segments of 103 anesthetized rats were functionally isolated while animals breathed spontaneously. Ammonia vapor was delivered into the laryngeal segment to measure laryngeal reflex reactivity. We found that the laryngeal pH 5-pepsin treatment doubled the reflex apneic response to ammonia, whereas laryngeal pH 7.4-pepsin, pH 2-pepsin, and pH 5-denatured pepsin treatment had no effect. Histological examination revealed limited laryngeal inflammation and epithelial damage after pH 5-pepsin treatment and more severe damage after pH 2-pepsin treatment. In rats that had received the laryngeal pH 5-pepsin treatment, the apneic response to ammonia was abolished by either denervation or perineural capsaicin treatment (PCT; a procedure that selectively blocks capsaicin-sensitive afferent fibers) of the superior laryngeal nerves, but was unaffected by perineural sham treatment. LAH was prevented by laryngeal application of either dimethylthiourea (DMTU; a *OH scavenger) or deferoxamine (DEF; an antioxidant for *OH), but was unaltered by the DMTU vehicle or iron-saturated DEF (ineffective DEF). LAH reappeared after recovery from PCT, DMTU, or DEF treatment. We conclude that 1) laryngeal insult by pepsin at a weakly acidic pH, but not at acidic pH, can produce LAH; and 2) LAH is probably mediated through sensitization of the capsaicin-sensitive laryngeal afferent fibers by a *OH mechanism.

Action Potentials↗

PubMed2006

Effect of pepsin on laryngeal stress protein (Sep70, Sep53, and Hsp70) response: role in laryngopharyngeal reflux disease.

OBJECTIVES: The objectives of this study were to define the conditions that give rise to a stress protein response in laryngeal epithelium and to investigate whether and how stress protein dysfunction contributes to reflux-related laryngeal disease. METHODS: Western analysis was used to measure stress protein (squamous epithelial proteins Sep70 and Sep53 and heat shock protein Hsp70) and pepsin levels in esophageal and laryngeal tissue specimens taken from both normal control subjects and patients with pH-documented laryngopharyngeal reflux (LPR) who had documented lesions, some of whom had laryngeal cancer. A porcine organ culture model was used to examine the effects of low pH and pepsin (0.1% porcine pepsin A) on stress protein levels. A laryngeal squamous carcinoma (FaDu) cell line was used to examine uptake of human pepsin 3b-tetramethyl-5 and -6 isothiocyanate. RESULTS: Sep70, Sep53, and Hsp70 were found to be expressed at high levels, and pepsin was not detected, in esophageal and laryngeal specimens taken from normal control subjects and in esophageal specimens taken from LPR patients. The patients with LPR were found to have significantly less laryngeal Sep70 (p = .027) and marginally less laryngeal Sep53 (p = .056) than the normal control subjects. Laryngeal Hsp70 was expressed at high levels in the LPR patients. The patients with laryngeal cancer had significantly lower levels of Sep70, Sep53 (p < .01), and Hsp70 (p < .05) than the normal control subjects. A significant association was found between the presence of pepsin in laryngeal epithelium from LPR patients and depletion of laryngeal Sep70 (p < .001). Using the organ culture model, we demonstrated that laryngeal Sep70 and Sep53 proteins are induced after exposure to low pH. However, in the presence of pepsin, Sep70 and Sep53 levels are depleted. Confocal microscopy analysis of cultured cells exposed to labeled pepsin revealed that uptake is by receptor-mediated endocytosis. CONCLUSIONS: These findings suggest that receptor-mediated uptake of pepsin by laryngeal epithelial cells, as may occur in LPR, causes a change in the normal acid-mediated stress protein response. This altered stress protein response may lead to cellular injury and thus play a role in the development of disease.

Adolescent↗

PubMed1988

Pepsins and the mucus barrier in peptic ulcer disease.

Studies show that the gastroduodenal mucosal barrier is damaged by pepsin under conditions in which it is resistant to acid alone. The continuous layer of adherent mucus gel provides a diffusion barrier to luminal pepsin, preventing its access to the underlying epithelium. Pepsin has mucolytic activity and will progressively digest the adherent mucus layer at its luminal surface, although normally this is balanced by secretion of new mucus to maintain a continuous barrier. In peptic ulcer disease the proportion of peptic activity in gastric juice attributable to pepsin type 1 is significantly raised (four to five-fold). Pepsin 1 has increased mucolytic activity compared with the major component, pepsin 3, both at the optimal pH of 2 (twofold increase in activity) and at higher pH values up to pH 5 (sixfold increase in activity at pH 4). Structural studies show that the gel forming polymeric mucin of the antral adherent mucus barrier is deficient in peptic ulcer disease. This breakdown of the mucus barrier in peptic ulcer patients can be attributed to the increased pepsin activity of gastric juice seen in this disease, although other explanations are also possible. The increased pepsin activity of gastric juice in peptic ulcer patients is compatible with the concept 'no acid, no pepsin, no ulcer'.

Gastric Acid↗

PubMed2004

The effects of chronic consumption of heroin on basal and vagal electrical-stimulated gastric acid and pepsin secretion in rat.

OBJECTIVE: Addiction to opium and heroin is not only an important social and individual problem in the world but it also affects the human physiology and multiple systems. The aim of this study is to determine the effects of chronic heroin consumption on basal and vagus electrical-stimulated total gastric acid and pepsin secretion in rats. METHODS: The study was carried out in the Department of Physiology, Kerman University of Medical Sciences, Iran from August 2002 to June 2003. Both male and female rats weighing 200-250 g were used. Rats received daily doses of heroin intraperitoneally starting from 0.2 mg/kg to 0.1 mg/kg/day up to the maintenance level of 0.7 mg/kg and continued until day 12. After anesthesia, tracheotomy and laparotomy, gastric effluents were collected by washout technique with a 15 minutes interval. The total titrable acid was measured by manual titrator, and the total pepsin content was measured by Anson's method. Vagal electrical stimulation was used to stimulate the secretion of acid and pepsin. RESULTS: Heroin results in a significant decrease in total basal acid and pepsin secretions (4.10 +/- 0.18 mmol/15 minutes versus 2.40 +/- 0.16 mmol/15 minutes for acid, p<0.01, and 3.63 +/- 0.18 mg/15 minutes versus 3.11+/- 0.18 mg/15 minutes for pepsin, p<0.05). But, it does not produce any significant changes in acid and pepsin secretions in vagotomized condition. Heroin also causes a significant decrease in vagal-electrically stimulated acid and pepsin secretions (14.70 +/- 0.54 mmol/15 minutes versus 4.30 +/- 0.21 mmol/15 minutes for acid, p<0.01, and 3.92 +/-0.16 mg/15 minutes versus 3.37+/- 0.16 mg/15 minutes for pepsin, p<0.05). CONCLUSION: Heroin consumption decreases the total gastric basal and vagus stimulation of acid and pepsin secretion, but not in vagotomized condition. Heroin may decrease acid secretion by inhibiting vagal release of acetylcholine within the gastric wall. Other probable mechanisms include: presynaptic inhibition of acetylcholine release or depressing the vagal center, inhibition of pentagastrin induced acid secretion, inhibitory effects via central mechanisms, probably mediated by the opiate receptors. Further studies are needed to recognize the actual mechanism.

Animals↗

PubMed1987

The effects of prostaglandin E1 on the pepsin activities in gastric mucosa and juice.

Prostaglandin E1 elevated pepsin activity in gastric mucosa but lowered pepsin activity in the gastric juice of rats treated by pylorus ligation and intragastric administration of hydrochloric acid. In these animals zymogen granules with low electron density were numerous in the gastric chief cells following prostaglandin E1 treatment. The prostaglandin E1-induced increase in mucosal pepsin activity was slightly inhibited by actinomycin D and there was no apparent increase in 3H-thymidine incorporation into gastric mucosa following treatment with prostaglandin E1. It is suggested that prostaglandin E1 causes an elevation of pepsin activity in the gastric mucosa by stimulating pepsin synthesis and perhaps also by facilitating pepsin release from zymogen granules. However, it also appears to inhibit pepsin release from the mucosa into the gastric cavity judging by the decrease of pepsin activity in gastric juice. The reduced pepsin activity in gastric juice may account, in part, for the reported anti-ulcerative action of prostaglandin.

Animals↗

PubMed1984

Pepsin secretion: neurohumoral regulation and drug effects.

The regulation of pepsin secretion was studied in the in vitro perfused mouse stomach. In contrast to acid secretion, basal pepsin release was not inhibited by 10(-4) M carbonyl cyanide m-chlorophenylhydrazine (CCCP) and by N2-induced hypoxia. Both secretions were not affected by 10(-3) M cimetidine, 10(-3) M atropine or cycloheximide (2 mg i.p. + 10(-5) M). Secretory responses to classical stimulants were similar to those obtained under in vivo conditions: carbamylcholine (CCH) and histamine stimulated acid and pepsin secretion in parallel, with a maximal pepsin/acid ration of 34 +/- 4 (mean +/- SEM) and 40 +/- 5, respectively. CCH-induced pepsin secretion was inhibited by atropine and pirenzepine. Dibutyrylic cyclic AMP(db-cAMP) strongly stimulated pepsin release. This stimulation was partially inhibited by trifluoperazine. Pentagastrin was a weak stimulant of pepsin secretion (pepsin/acid ratio: 10 +/- 3), whereas 10(-4) M bombesin and 10(-6) M salmon calcitonin had no effect. Omeprazole (H168/68) strongly inhibited basal acid secretion and stimulated pepsin release in a dose-and energy-dependent fashion. In contrast to acid, basal pepsin release probably represents an 'overflow secretion'. Although pepsin and acid are usually stimulated in parallel, dissociated responses are obtained under in vitro conditions, indicating that separate regulatory pathways exist.

Animals↗

PubMed1984

Pepsin like enzyme in macrophages and its role in the immune system.

Phagocytosis by DBA/2 or autoimmune NZB mouse macrophages of sheep erythrocytes, which are heterologous to these macrophages, was enhanced by mouse pepsin, whereas phagocytosis of homologous erythrocytes was suppressed by pepsin. Antibody production by DBA/2 or NZB mouse lymphocytes against heterologous erythrocytes was also enhanced by pepsin, but autoantibody production by NZB mouse lymphocytes was suppressed by pepsin. An acid protease present in macrophages was found to have biochemical properties quite close to those of pepsin, with regard to molecular weight, isoelectric point, and 50% inhibition dose of pepstatin. This acid protease was immunochemically identical with pepsin, reacting with anti-pepsin antibody. Taken together, these results indicate that pepsin modulates macrophage functions and that the pepsin like enzyme in macrophages may play important roles in the regulation of phagocytosis by macrophages and in antibody production.

Animals↗

PubMed1981

Physiological stimulation of pepsin secretion. The role of vagal innervation.

The studies were performed on eight double-pouch dogs with one vagally innervated Amdrup pouch (AP) and one denervated Heidenhain pouch (HP), allowing comparison of pepsin secretion from innervated and denervated mucosa at the same time in the same animal. Food stimulation was done with a mixture of liver, heart, and bonemeal in doses of 1.25, 2.5, 5, 10, and 20 g/kg body weight, plus maximal stimulation by repeated meals of 5 g/kg every 15 min up to 10 times. 'Non-active' secretion of pepsin was determined by instillation in the pouches of 0.1 M and 0.005 M HCl dissolved in 0.15 M NaCl. The pepsin secretion in the HP equalled the 'non-active' output for all doses of food. In the innervated pouch there was an immediate, very high pepsin output similar to the response that can be elicited by 2-deoxy-D-glucose and bethanechol chloride. The secretion of pepsin was gradually reduced, but it was, as long as the volume and electrolyte secretion lasted. well above the 'non-active' level. The results show that stimulation of pepsin secretion by food is completely dependent on intact vagal innervation. The volume and acid output were increased as the dose of food was increased, but the concentration of pepsin was stepwise reduced when the volume increased, resulting in approximately the same output of pepsin for all doses of food. The pepsin to acid ratio was statistically higher in juice secreted from innervated than from denervated mucosa for all doses of food, for lower doses of histamine and pentagastrin, and for higher doses of bethanechol chloride.

Animals↗

PubMed1994

Pepsin hydrolysis of the adherent mucus barrier and subsequent gastric mucosal damage in the rat: effect of diosmectite and 16,16 dimethyl prostaglandin E2.

BACKGROUND AND OBJECTIVE: The gastroduodenal mucus layer is progressively eroded at its luminal surface as a consequence of pepsin mucolysis. Diosmectite binds to gastric mucus and modifies its rheological properties. Prostaglandins are well-known mucus secretagogues. The aim of this study is to describe interactions of diosmectite and 16,16 dimethyl prostaglandin E2 on adherent gastroduodenal mucus and pepsin mucolysis in the rat. METHODS: Instillation of pepsin (1 or 2 mg.mL-1 at pH1 or pH2) into the pylorus ligated stomach of anaesthetised rats resulted in progressive disruption of the adherent mucus layer and a large, significant, increase in soluble degraded mucin compared to that following instillation of HCl pH1 or pH2. Pepsin (2 mg.mL-1), instillation over 2 hours, but not HCl alone, consistently resulted in small focal, haemorrhagic mucosal lesions, significant bleeding into the lumen and histologically, localised punctate ulcers in an otherwise intact epithelium. Diosmectite (500 mg.kg-1) and 16,16 dimethyl prostaglandin E2 were given by oro-gastric intubation. RESULTS: Diosmectite, given 30 minutes beforehand, inhibited breakdown of the adherent gastric mucus barrier by pepsin in vivo. When administered up to 16 hours prior to the experiment, diosmectite prevented pepsin induced gastric mucosal haemorrhage and histological epithelial damage. Substantial amounts of diosmectite (39.6 micrograms/mm2, equivalent in volume to layer 93 microns thick) were bound to the gastric mucosa 30 minutes after administration. Diosmectite (100:1 by weight to enzyme) completely inhibited pepsin hydrolysis of protein in vitro. Topical 16,16 dimethyl prostaglandin E2, 5 micrograms.kg-1 increased the thickness of the adherent mucus layer by two-fold. Both doses of the prostaglandin prevented pepsin induced gastric mucosal haemorrhage and histological epithelial damage. CONCLUSIONS: These results show that both diosmectite and prostaglandin increase the effectiveness of the mucus barrier against mucosal damage by pepsin in vivo.

16,16-Dimethylprostaglandin E2↗

PubMed1993

Conformational instability of the N- and C-terminal lobes of porcine pepsin in neutral and alkaline solutions.

Pepsin contains, in a single chain, two conformationally homologous lobes that are thought to have been evolutionarily derived by gene duplication and fusion. We have demonstrated that the individual recombinant lobes are capable of independent folding and reconstitution into a two-chain pepsin or a two-chain pepsinogen (Lin, X., et al., 1992, J. Biol. Chem. 267, 17257-17263). Pepsin spontaneously inactivates in neutral or alkaline solutions. We have shown in this study that the enzymic activity of the alkaline-inactivated pepsin was regenerated by the addition of the recombinant N-terminal lobe but not by the C-terminal lobe. These results indicate that alkaline inactivation of pepsin is due to a selective denaturation of its N-terminal lobe. A complex between recombinant N-terminal lobe of pepsinogen and alkaline-denatured pepsin has been isolated. This complex is structurally similar to a two-chain pepsinogen, but it contains an extension of a denatured pepsin N-terminal lobe. Acidification of the complex is accompanied by a cleavage in the pro region and proteolysis of the denatured N-terminal lobe. The structural components that are responsible for the alkaline instability of the N-terminal lobe are likely to be carboxyl groups with abnormally high pKa values. The electrostatic potentials of 23 net carboxyl groups in the N-terminal domain (as compared to 19 in the C-terminal domain) of pepsin were calculated based on the energetics of interacting charges in the tertiary structure of the domain. The groups most probably causing the alkaline denaturation are Asp11, Asp159, Glu4, Glu13, and Asp118.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Revised 2.3 A structure of porcine pepsin: evidence for a flexible subdomain.

A revised three-dimensional crystal structure of ethanol-inhibited porcine pepsin refined to an R-factor of 0.171 at 2.3 A resolution is presented and compared to the refined structures of the fungal aspartic proteinases: penicillopepsin, rhizopuspepsin, and endothiapepsin. Pepsin is composed of two nearly equal N and C domains related by an intra dyad. The overall polypeptide fold and active site structures are homologous for pepsin and the fungal enzymes. The weak inhibition of pepsin by ethanol can be explained by the presence of one or more ethanol molecules, in the vicinity of the active site carboxylates, which slightly alter the hydrogen-bonding network and which may compete with substrate binding in the active site. Structural superposition analysis showed that the N domains aligned better than the C-domains for pepsin and the fungal aspartic proteinases: 107-140 C alpha pairs aligned to 0.72-0.85 A rms for the N domains; 64-95 C alpha pairs aligned to 0.78-1.03 A rms for the C domains. The major structural difference between pepsin and the fungal enzymes concerns a newly described subdomain whose conformation varies markedly among these enzyme structures. The subdomain in pepsin comprises nearly 100 residues and is composed of two contiguous segments within the C domain (residues 192-212 and 223-299). the subdomain is connected, or "hinged," to a mixed beta-sheet that forms one of the structurally invariant, active site psi-loops. Relative subdomain displacements as large as a 21.0 degrees rotation and a 5.9 A translation were observed among the different enzymes. There is some suggestion in pepsin that the subdomain may be flexible and perhaps plays a structural role in mediating substrate binding, determining the substrate specificity, or in the activation of the zymogen.

Amino Acid Sequence↗

PubMed1978

Osmotic stimulation of pepsin secretion in the rat.

The effect of the osmolarity of intragastric instillates on pepsin secretion was studied in rats anaesthetised with urethane. Irrigation of the stomach with solutions of sucrose and NaCl, resp. caused a concentration-dependent increase in pepsin output. A stimulation was observed already by hypotonic solutions and the maximal effect was obtained by 300 m-osmole/l of sucrose and by 600 m-osmole/l of NaCl (13- and 10-fold stimulation resp.). A similar time course in the increase of pepsin output was produced by hyperosmotic solutions (600 m-osmole/l) of sucrose, urea, NaCl and choline chloride. Pepsin output was stimulated maximally within 30 min and decreased thereafter, but remained at about 4--6-fold higher levels than during the previous irrigation with distilled water. Replacement of hyperosmotic instillates by distilled water reduced pepsin secretion to the initial level. Hypertonic ethanol (600 m-osmole/l) increased pepsin output only slightly. Vagotomy, pretreatment with atropine (1 mg/kg i.v.) or cimetidine (5 mg/kg i.v.), local anesthesia of the gastric mucosa with 4% lidocaine or intravenous infusion of PGE2 (2 microgram/kg X min) did not antagonise the stimulation of pepsin output induced by hyperosmotic NaCl (600 m-osmole/l). The results indicate that the increase of the osmolarity of intragastric instillates stimulates pepsin secretion in the rat without involvement of neural (vagal or local cholinergic reflexes) or hormonal mechanisms (release of gastrin) which are known to stimulate gastric secretion in the gastric phase.

Animals↗

PubMed1981

Effect of topical application of amino acids on gastric pepsin secretion in the rat.

The effect of amino acids and other chemicals of intragastric perfusion on pepsin secretion was studied in anaesthetized rats. Irrigation of the stomach with glycine caused concentration-dependent increase in pepsin output, but not in acid output. Pepsin stimulatory effect was decreased by an increase of the carbon chain between the amino group and carboxyl group of glycine and by transposing the amino group from alpha- to gamma-position in amino-n-butyric acid. Acidification of perfusate, a local irrigation of lidocaine and an intravenous infusion of atropine reduced but did not abolish the pepsin response to chemical stimulation. Since serum gastrin level was not changed from basal levels during pepsin secretion induced by amino acids, the mechanism of chemical stimulation appears to be gastrin-independent. The comparison of the secretagogue activity of amino acids shows that glycine exhibited the strongest stimulation of pepsin output, reaching 208% of the response to tetragastrin at the dose of 8 microgram/kg/hour. All other amino acids tested were found to stimulate pepsin secretion, whereas bovine serum albumin and hydrochloric acid were inert in this respect. The result indicates that the chemical stimulation of the stomach by amino acids is capable of inducing pepsin secretion by a local, gastrin-independent mechanism sensitive to pH and related to the molecular configuration of amino acids.

Amino Acids↗

PubMed2005

Gastric antibacterial efficiency is different for pepsin A and C.

The gastric lumen represents a bactericidal barrier, whose major components are an acidic pH and a family of isoenzymes of the gastric aspartate protease, pepsin. To evaluate whether specific pepsins are specialized in antibacterial protection, we tested their effects on the gastric pathogen Helicobacter pylori. In a recent study we found pepsin to affect the motility of the bacteria, one of its most important virulence factors. We were able to show that the antibacterial effect of pepsin occurs in two phases: rapid loss of motility and subsequent destruction. In the present study we used the rapid pepsin-induced bacterial immobilization as a marker of antibacterial efficiency. The proteolytic activity of different pepsins was normalized to values between 2 and 200 U/ml in the hemoglobin degradation test of Anson, performed at pH 2 and 5. We found that pepsin C completely inactivates H. pylori at proteolytic activities of 2 (pH 5) and 20 (pH 2) U/ml. In contrast, the activities of pepsin A and chymosin required to affect Helicobacter motility were ten times higher.

Animals↗

PubMed2006

Essential role of pepsin in pathogenesis of acid reflux esophagitis in rats.

Pepsin, a protease activated by gastric acid, is a component of the refluxate, yet the role of pepsin in the pathogenesis of reflux esophagitis has not been well studied. In the present study, we examined the effect of pepstatin, a specific inhibitor of pepsin, on acid reflux esophagitis. Acid reflux esophagitis was induced in rats by ligating both the pylorus and the forestomach for 3 or 4 hr. Pepstatin, ecabet Na (the anti-ulcer drug), and L-glutamine were administered intragastrically after the ligation. Pepstatin or ecabet Na, given intragastrically, significantly prevented esophageal lesions, even though they did not affect basal acid secretion in pylorus-ligated rats. Pepstatin significantly inhibited pepsin activity in vivo and in vitro, while ecabet Na inhibited this activity in vitro. By contrast, L-glutamine given intragastrically aggravated the lesions in a dose-dependent manner, but even in the presence of L-glutamine the development of esophageal lesions was totally prevented by coadministration of pepstatin or ecabet Na. L-Glutamine increased the pH of gastric contents to approximately 2.0, the optimal pH for the proteolytic activity of pepsin in vitro. In addition, intragastric administration of exogenous pepsin worsened the severity of esophageal damage. These results suggest that pepstatin is highly effective against acid reflux esophagitis, without influencing acid secretion, while L-glutamine aggravated these lesions by increasing the pepsin activity by shifting the intraluminal pH to the optimal pH range for proteolytic action. It is assumed that pepsin plays a major pathogenic role in the development of acid reflux esophagitis.

Animals↗