Inhibition of gastric mucosal mucin receptor by H. pylori lipopolysaccharide: effect of ebrotidine.
1. H. pylori infection causes the loss of mucus coat continuity and its patchy appearance. Here, we present evidence that the bacterium, through its cell wall lipopolysaccharide, disrupts the interaction between mucin and its mucosal receptor, and that ebrotidine is capable of counteracting this process. 2. The receptor for mucin, isolated from the solubilized gastric epithelial cell membrane by affinity chromatography on Sepharose-bound wheat germ agglutinin, displayed a molecular weight of 97 kDa and exhibited specific affinity towards mucin-coated surface. 3. The mucin binding to the receptor was susceptible to the inhibitin by H. pylori lipopolysaccharide and reached a maximum of 91%. This effect of the lipopolysaccharide was counteracted by ebrotidine, which caused a dose-dependent relief of the lipopolysaccharide inhibitory effect with maximum restoration in mucin-receptor binding of 51% at 60 microliters/ml ebrotidine. 4. The results show that H. pylori, through its lipopolysaccharide, is capable of disrupting the integrity of mucus perimeter of gastric mucosal defense and that antiulcer agent, ebrotidine, counteracts this untoward effect.
Slomiany
B L
BL
Research Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103-2400, USA.
Piotrowski
J
J
Murty
V L
VL
Slomiany
A
A
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001557:Benzenesulfonates / Q000494:pharmacology*; D005752:Gastric Mucins / Q000378:metabolism*; D016480:Helicobacter pylori / Q000737:chemistry / Q000187:drug effects*; D008070:Lipopolysaccharides; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*
D000897:Anti-Ulcer Agents; D001557:Benzenesulfonates; D005752:Gastric Mucins; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D013844:Thiazoles; C085661:mucin receptor; C075156:ebrotidine