Inhibition of cholera toxin binding to membrane receptors by pig gastric mucin-derived glycopeptides: differential effect depending on the ABO blood group antigenic determinants.
The capacity of pig gastric mucin-derived glycopeptides to interfere with the binding of cholera toxin (CT) to membrane receptors was studied. Two types of glycopeptide preparations with or without human blood group A antigenic activity were assayed for comparison in a system in which the target for the toxin was rat erythrocyte ghosts. Blood group A-active glycopeptides (A+ glycopeptides) were more potent inhibitors for the toxin binding than those lacking group A activity (A- glycopeptides). The mean values of the 50% inhibitory dose revealed that the A+ glycopeptide preparations were 6.6-fold-more potent inhibitors than the A- ones (P less than 0.001). The inhibitory capacity of the different A+ glycopeptide preparations was not directly proportional to the group A antigenic titer. The A+ glycopeptides showed a higher capacity than the A- glycopeptides to interact with the toxin as revealed by CT-glycopeptide complex formation, which could be detected by Sephacryl S-400 chromatography. This result suggests that glycopeptide inhibition of CT binding to the erythrocyte ghosts is mediated by a competition between the GM1 receptors and the glycopeptides for the toxin. The differential effect between both types of glycoconjugates was independent of the way of measuring the amount of glycopeptides used (dry weight, carbohydrate or protein content). The existence in the gastrointestinal tract of mucins not carrying or carrying different ABO blood group determinants, which could behave as more or less potent inhibitors of CT binding to membrane receptors, may help to explain the relationship between ABO blood groups and severity of cholera.
Departamento de Quimica Biologica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, CIQUIBIC-CONICET, Argentina.
C G
CG
Monferran
G A
GA
Roth
F A
FA
Cumar
D000017:ABO Blood-Group System; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002772:Cholera Toxin / Q000378:metabolism*; D000939:Epitopes; D005753:Gastric Mucosa / Q000276:immunology*; D006020:Glycopeptides / Q000276:immunology / Q000494:pharmacology*; D006023:Glycoproteins / Q000494:pharmacology*; D009077:Mucins / Q000276:immunology / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000378:metabolism*; D013552:Swine
D000017:ABO Blood-Group System; D000939:Epitopes; D006020:Glycopeptides; D006023:Glycoproteins; D009077:Mucins; D011971:Receptors, Immunologic; C047874:gastric mucus glycoproteins; D002772:Cholera Toxin