Mucolysis of the colonic mucus barrier by faecal proteinases: inhibition by interacting polyacrylate.
1. Mucolytic (mucus solubilizing) activity in human faeces has been characterized with both purified human and pig colonic mucin and shown to be mediated by proteolysis. 2. Mucolytic activity was demonstrated by: (i) a drop in mucin viscosity; (ii) a substantial reduction in mucin size, from polymer to degraded subunit, as assessed by Sepharose CL-2B gel filtration; (iii) formation of new N-terminal peptides. 3. Mucolytic activity was also followed in faecal extracts by its proteolytic activity using standard succinyl albumin substrate. Proteolysis extended over the pH range 4.5-11.0. Proteolysis was inhibited at pH 7.5 by soybean trypsin inhibitor and phenylmethanesulphonyl fluoride, suggesting the presence of serine proteinases. 4. The polyacrylate carbomer (934P) inhibited both mucolysis of pig colonic mucin and proteolysis of succinyl albumin. 5. Interaction between the polyacrylate (carbomer 934P) and purified human and pig colonic mucin was demonstrated by a marked synergistic increase in solution viscosity (360% above control). 6. The results demonstrate the presence of a mucolytic activity in the human colonic lumen that has the potential to degrade the mucus barrier, and that polyacrylates inhibit this mucolysis and interact to strengthen the colonic mucus barrier. Polyacrylates may therefore have therapeutic potential in inflammatory bowel disease where luminal proteolytic activity can be raised.
Hutton
D A
DA
Department of Physiological Sciences, University of Newcastle upon Tyne, Medical School, U.K.
Pearson
J P
JP
Allen
A
A
Foster
S N
SN
D000180:Acrylic Resins / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000418:Albumins / Q000378:metabolism; D000818:Animals; D002850:Chromatography, Gel; D003106:Colon / Q000201:enzymology; D005243:Feces / Q000201:enzymology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D009077:Mucins / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013552:Swine; D014783:Viscosity
D000180:Acrylic Resins; D000418:Albumins; D009077:Mucins; D011480:Protease Inhibitors; D015842:Serine Proteinase Inhibitors; C006903:carbopol 940; D010447:Peptide Hydrolases