Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pepsin 1, the ulcer-associated pepsin, occurred significantly more frequently in the gastric juice of those patients with duodenal ulcer who did not secrete A, B, or H antigens into gastric juice than in those secreting these antigens. This observation may explain the increased proportion of such non-secretors among patients with duodenal ulceration. In patients with gastric ulcer and non-ulcer dyspepsia, and in a miscellaneous group of patients, there was no association of pepsin 1 secretion with secretor status, suggesting that the association noted in duodenal ulceration is an indirect rather than a direct one. No increase of pepsin 1 occurred in group O patients with peptic ulcer, so that the increased proportion of such patients in peptic ulcer does not arise from differences in pepsin 1 secretion.
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PMID:Hereditary aspects of duodenal ulceration: pepsin 1 secretion in relation to ABO blood groups and ABH secretor status. 11 57

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.
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PMID:Effects of an orally administered prostaglandin analogue (16, 16-dimethyl prostaglandin E2) on human gastric secretion. 115 77

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'.
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PMID:Pepsins and the mucus barrier in peptic ulcer disease. 314 8

Pepsin is a potent proteolytic enzyme stored and secreted by chief cells in an inactive precursor form, pepsinogen. Its secretion is modulated by both cAMP and calcium-dependent mechanisms. Abnormalities in levels of pepsinogen and its various isozymogens have been linked clinically, epidemiologically, and experimentally to peptic ulcer disease and gastric carcinoma. The ulcerogenesis of pepsin stems from its ability to breach gastroduodenal mucosal barriers. Furthermore, certain isozymogens seems abundant and hyperactive in patients with peptic ulcer disease. The etiology and significance of low pepsinogen levels with disproportionate elevations of pepsinogen II and pepsin 5 in gastric cancer and its precursors is less clear. Further exploration of the patho-physiologic role of pepsin is likely to be of considerable importance in initiating further advances in the understanding and treatment of upper gastrointestinal disease.
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PMID:Pepsinogen. Prolate ellipsoid or unrecognized pathogen? 330 25

The synthetic trimethyl prostanoid Ro 22-6923 was studied for its effects on histamine-stimulated gastric acid secretion in Heidenhain pouch dogs. The prostanoid (at a p.o. dose as low as 0.05 mg/kg) produced significant inhibition of gastric acid secretion induced by 12 micrograms/kg/h of histamine for 5 h. A dose of 0.5 mg/kg p.o. produced a significant antisecretory effect within 45 min that lasted for 8.5 h. Cimetidine (5 mg/kg p.o.) produced an inhibitory effect on acid output equivalent to the 0.5-mg/kg dose of Ro 22-6923, but the duration of the cimetidine effect was less than 6 h. Administration of Ro 22-6923 i.v. (0.25 mg/kg) inhibited acid output for longer than 8 h. Against a 25-micrograms/kg/h histamine challenge, Ro 22-6923 (0.5 and 1.0 mg/kg) inhibited acid output to an equal degree but for a longer duration than cimetidine (5 mg/kg). Pepsin output was totally inhibited by 0.5 mg/kg of Ro 22-6923, whereas 5 mg/kg of cimetidine inhibited pepsin output by approximately 60%. Pepsin activity in the gastric juice was reduced by Ro 22-6923 and was increased by cimetidine. Blood flow, as estimated by the aminopyrine clearance technique, was reduced slightly by Ro 22-6923 and cimetidine. However, the ratio of clearance to acid secretory rate increased with both compounds, suggesting a direct effect of Ro 22-6923 and cimetidine on acid secretion at the parietal cell level. The results suggest that Ro 22-6923 may be a useful therapeutic agent for peptic ulcer disease in humans.
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PMID:Effect of the synthetic prostanoid Ro 22-6923 on gastric secretion and blood flow in Heidenhain pouch dogs. 391 6

Gastroduodenal mucus is present as a water insoluble gel adherent to the mucosal surface and as a viscous mobile solution in the lumen. The protective properties of the mucus against acid (with bicarbonate), pepsin (diffusion barrier) and mechanical damage depend on the quality (structure) and quantity (thickness) of the adherent mucus gel layer. Adherent mucus is a viscoelastic gel which is 95% (v/v) water. It is permeable to ions and smaller molecules (Mr c. 1000), but is impermeable to large proteins (Mr c. 17,000) including pepsins. However, mucus is solubilized rapidly by pepsin, more slowly (greater than or equal to 1 h) by thiol agents, and is unchanged following exposure to bile, acid and ethanol (less than 40%). Glycoprotein macromolecules (Mr greater than or equal to 2 X 10(6] are the structural components of the mucus gel and have a polymeric structure of glycoprotein subunits (Mr c. 5 X 10(5), for gastric mucus) joined by disulphide bridges between their protein cores. This glycoprotein polymerization, which is essential for gel formation and hence function, is the site of action of proteolytic enzymes and thiol agents. The glycoprotein polymeric structure is deficient in antral mucus from patients with peptic ulcer disease. In vivo, adherent mucus forms a thin but continuous cover of variable thickness (50-450 micron in man, about two-fold less in rat) over the gastroduodenal mucosa. Pepsin in gastric juice will rapidly dissolve this mucus cover and can be active up to luminal pH values of 5.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adherent and soluble mucus in the stomach and duodenum. 393 55

Acid and pepsin have been designated the "aggressive factors" in peptic ulcer because they are essential for ulcer formation and because a reduction in their luminal concentrations is usually followed by ulcer healing. Acid enables peptic aggression by converting pepsinogen to pepsin, by providing the highly acidic pH required for pepsin activity, and by denaturing proteins, thereby increasing their susceptibility to the action of pepsin. Pepsin causes peptic aggression by hydrolyzing peptide linkages which bind together the constituent amino acids of proteins. The first step in this reaction is the formation of a complex between the active site of pepsin and the protein substrate. Sucralfate, which is the basic aluminum salt of sucrose octasulfate, inhibits this step by forming an electrostatic complex with proteins. As such, sucralfate inhibits peptic aggression without decreasing acid-pepsinogen secretion or raising intragastric pH. Because of its affinity for proteins and its insolubility and inherent viscosity in acid, sucralfate forms a physical coating over the ulcer crater. This coating further inhibits peptic aggression by producing a barrier to the diffusion of acid and pepsin. Additionally, the basic aluminum moieties of sucralfate may serve to buffer hydrogen ions as they attempt to permeate the viscous layer. The sum of these effects appears to explain the ability of sucralfate to accelerate the rate of healing of peptic ulcer.
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PMID:Inhibition of peptic aggression by sucralfate. The view from the ulcer crater. 641 6

Gastric juice was collected from 27 children for 9 to 21 hr following cardiac surgery, from 4 further children during and following cardiac surgery, and from 3 children who had not undergone surgery. Each sample was analyzed for hydrogen ion and pepsin content. The pH of the postoperative secretions from 26 patients was 1.25 to 5.30, and the mean hydrogen ion concentration was 60.1 mmol/liter (range, 21.5 to 119.3 mmol/liter). The mean peptic activity (83.0 units/ml; range, 42.4 to 158.4 units/ml) was not age related and was significantly higher than that of the basal and pentagastrin-stimulated secretion and similar to that of vagally stimulated secretion of adults with peptic ulcer. The pepsin:hydrogen ion and pepsin 1:total pepsin ratios also resembled those of vagally stimulated secretion. During the first 90 min of cardiac surgery, the pH of aspirated gastric juice was 1.40 to 4.90, the hydrogen ion concentration was 15.8 to 72.3 mmol/liter, peptic activity was 39.2 to 164.0 units/ml (mean, 97.2 units/ml). Pepsin 1 was present in all samples. Aspirates from 3 unoperated children had low total peptic activity and only trace amounts of pepsin 1. Children from the age of 5.5 months thus have the capacity to secrete all the major pepsins, including pepsin 1. The findings suggest that vagal stimulation of gastric secretion was occurring during the postoperative period.
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PMID:Secretion of pepsins and hydrogen ions in the stomach of children undergoing cardiac surgery. 677 Mar 29

Carbenoxolone may bind to enzymes, inhibiting or activating them. Enzymes inhibited are human pepsins 1, 3 and 5, human pepsinogens 1, 3 and 5, swine pepsin, bovine trypsin, bovine chymotrypsin, porcine elastase, human gastric proteinase 2, human gastric prostaglandin 15-OH dehydrogenase and delta-5 reductase, and pronase. Enzymes activated are papain, bovine carboxypeptidase and gastric microsomal glycosyl transferase. Enzymes unaffected are human pancreatic amylase and porcine pancreatic lipase. Binding occurs away from the active site; inhibition thus occurs when binding impedes access of substrate to, or products from, the active site, and activation when access is facilitated. Carbenoxolone causes increased secretion of mucus; this action can be explained by activation of the gastric glycosyl transferases. Carbenoxolone also causes intraluminal loss of peptic activity and diminished secretion of pepsins; these actions are explained respectively by intraluminal inhibition of the pepsins and intramucosal inactivation of the pepsinogens, particularly of the peptic ulcer-associated enzyme, pepsin 1. The healing effect of carbenoxolone in peptic ulcer involves these actions together with a reduced turnover of gastric mucosal cells. Pepsins 1 and 3 have collagenolytic activity, causing release of alpha-chains from native collagens. Pepsin 1 is five-fold the more active. Carbenoxolone inhibits peptic collagenolysis.
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PMID:The actions of carbenoxolone on enzymes and their relation to its therapeutic effect. 678 51

To verify the effect of age on gastric secretions in gastric (GU) and duodenal ulcer (DU) patients, we carried out a retrospective study evaluating basal and stimulated gastric acid secretion in 427 peptic ulcer subjects aged between 12 and 73 years (GU = 74, DU = 353) in addition to studying gastric juice pepsin, serum pepsinogen group A (PGA) and gastrin in 175 patients (GU = 28, DU = 147). All subjects were then divided into groups according to their sex and age (< 30, 30-39, 40-49, 50-59 and > 60 years). Basal, maximal and peak acid outputs (BAO, MAO, PAO) were unchanged in the various age groups, though MAO and PAO were higher in males than females and in DU than in those with GU, even in the elderly (> 60 years). Pepsin and gastrin levels were unchanged at the various ages in GU and DU, while PGA was higher in males with DU aged 50 or over. This demonstrates that acid, pepsin and gastrin secretions do not change with age in ulcer patients. Acid secretion retains its typical distribution according to pathology (DU > GU) and sex (males > females), and also appears to have a fundamental pathogenetic role in peptic ulcer in the elderly.
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PMID:Effect of age on gastric acid, pepsin, pepsinogen group A and gastrin secretion in peptic ulcer patients. 795 81


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