Calcium binding to biliary mucins is dependent on sodium ion concentration: relevance to cystic fibrosis.
Because hypersecretion of gallbladder (GB) mucus occurs in gallstone formation and because binding of Ca(2+) to biliary lipids only accounts for 50% of the total Ca(2+) in GB bile, we investigated the binding of Ca(2+) to human biliary mucin. Biliary mucin was purified from GB bile and binding to Ca(2+) studied. Scatchard plot analysis suggested two binding sites. Removal of sialic acid by neuraminidase resulted in 10% reduction of Ca(2+) binding, whereas, sulfatase treatment reduced Ca(2+) binding by 30%. Using a hypotonic NaCl solution, Ca(2+) binding to mucin increased curvilinearly with mucin concentration. However, binding decreased with increasing ionic strength of the NaCl solution. We conclude that binding of Ca(2+) to mucin is effected mainly through sulfate. Binding to Ca(2+) can be displaced by Na(+). Ca(2+) binding to mucins is enhanced in the setting of low Na(+) concentrations. This phenomenon has pathophysiologic implications for the formation of thick mucus in cystic fibrosis epithelia.
Kuver
Rahul
R
Division of Gastroenterology, University of Washington School of Medicine, Seattle, WA 98195, USA. kuver@u.washington.edu
Lee
Sum P
SP
D001646:Bile / Q000378:metabolism; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007477:Ions; D007700:Kinetics; D009077:Mucins / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000494:pharmacology; D009439:Neuraminidase / Q000378:metabolism; D011485:Protein Binding; D012794:Sialic Acids / Q000378:metabolism; D012964:Sodium / Q000737:chemistry / Q000378:metabolism*; D012965:Sodium Chloride / Q000737:chemistry; D013429:Sulfatases / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism; D013696:Temperature
D007477:Ions; D009077:Mucins; D012794:Sialic Acids; D013431:Sulfates; D012965:Sodium Chloride; D012964:Sodium; D013429:Sulfatases; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid; D002118:Calcium