Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D00446 (Sucralfate)
 278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

We have established a new model for rat gastric epithelial cell (RGM1) damage caused by both acid and pepsin. Exposure of RGM1 to an acidified medium (pH 3.5-5.0) for 10-50 min decreased cell viability in a time- and pH-dependent manner. Pepsin (0.5-1.0 mg/mL) at pH 4.5 potentiated cell damage in a concentration-dependent manner. Based on these results, two types of cell damage models caused by incubation of cells at pH 4.0 and with pepsin (0.75 mg/mL) at pH 4.5 for 30 min, respectively, were established. The intracellular pH (pHi) gradually decreased with a decrease in medium pH and an increase in exposure time. At pH < or = 4.0, pHi reached approximately pH 6.3. Pepsin at pH 4.5 caused a further reduction in pHi compared with the acidified medium alone. Pepsin pre-incubated with pepstatin did not induce any cell damage. Pretreatment with sucralfate (0.1-3 mg/ mL) for 2 h significantly prevented cell damage caused at both pH 4.0 and with pepsin at pH 4.5 in a concentration-dependent manner. Sucralfate (3 mg/mL) significantly prevented the reduction in pHi at pH 4.0 or with pepsin at pH 4.5. 16,16-Dimethyl prostaglandin E2 (30 micrograms/mL) had no effect on either cell damage or pHi. These cell damage models involving RGM1 are useful for studying the mechanism underlying cell damage and for the screening of cytoprotective drugs.
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PMID:Characterization of a novel cell damage model induced by acid and pepsin using rat gastric epithelial cells: protective effect of sucralfate. 908 12