Comprehensive Physiology Wiley Online Library

Gastrointestinal Mucus

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Abstract

The sections in this article are:

1 Adherent Mucus Gel
1.1 In Vivo Continuity and Thickness
1.2 Physical and Permeability Properties
2 Isolated Mucin Glycoprotein
2.1 Technology
2.2 Mucin Carbohydrate Chain Structure
2.3 Protein Core of Mucins and Macromolecular Polymeric Structure
2.4 Gel‐Formation and Physical Properties of Mucins
2.5 Lipid and Protein Components of Mucus Secretions
3 Biosynthesis and Secretion of Mucus: Cellular Aspects
3.1 Mucus‐Secreting Cells
3.2 Mucin Biosynthesis
3.3 Secretion of Mucus
4 Secretion of Mucus: Measurement and Control
4.1 Measurement
4.2 Control of Secretion of Gastric Mucus
4.3 Control of Secretion of Intestinal and Colonic Mucus
5 Degradation of Mucus
6 Function of Mucus
Figure 1. Figure 1.

A: adherent gastric mucus viewed under bright field on a transverse section 1.6 mm thick) of rat gastric mucosa. Three distinct phases can be seen clearly: mucosa, mucus gel layer, and bathing solution. For method, see Kerss et al. 111. B: reepithelialized mucosa: rat gastric mucosa after exposure to 70% (vol/vol) ethanol for 45 s and rapid wash with 0.9% (wt/vol) sodium chloride followed by 0.9% (wt/vol) sodium chloride for 1 h. Mucosa was formalin fixed, embedded in paraffin wax, and sections were stained with periodic acid‐Schiff stain for mucin.

A courtesy of L. A. Sellers; B from Sellers et al. 209
Figure 2. Figure 2.

Diagram of a subunit of mucus glycoprotein structure showing glycosylated “bottle brush” and nonglycosylated regions. Subunits are joined by disulfide bridges to form overall linear polymeric mucins. Detailed tertiary structure of subunits within the polymeric mucin has not been elucidated.

Figure 3. Figure 3.

Composite diagram of proposed structures for typical branched oligosaccharides in human 223 and pig 219 gastric mucin glycoproteins showing the immunodeterminant blood group A and H (— — —) and I (‐ ‐ ‐) saccharide structures. Location of sulfate esters on the chains is not known. Fuc, fucose; Gal, galactose; GalNAc, N‐acetylgalactosamine; GlcNAc, N‐acetylglucosamine.

Figure 4. Figure 4.

Physical properties of pig gastric mucus in dilute solution (A) and in native mucus gel (B). A: dependence of solution viscosity of pig gastric mucus on glycoprotein concentration. Viscosity of the solution rises asymptotically with increased glycoprotein concentration until it assumes the properties of a gel at a glycoprotein concentration of ∼50 mg/ml 14,20. This can be explained by the large hydrated glycoprotein molecules at higher concentrations occupying the whole solution volume and their overlapping molecular domains interacting noncovalently to form the mucus‐gel matrix. Concentration of glycoprotein in gastric mucus (pig and human) is ∼50 mg/ml. Reduced or proteolytically degraded glycoprotein subunits have a low solution viscosity and do not form gel at high concentrations of glycoprotein. B: mechanical spectrum for pig gastric mucus showing a plot of elastic (storage modulus, —–) and viscous (loss modulus, —–) moduli against frequency of oscillatory deformations 20. Mucus gel is sandwiched between a flat plate and shallow cone and subjected to small deformations at different oscillatory frequencies without disrupting gel structure. From the magnitude and phase of stress generated in resistance to applied deformation the storage modulus G’ (elastic or solid component) and the loss modulus G” (viscous or liquid component) can be calculated. Native gastric mucus and mucus reconstituted from isolated glycoprotein have the behavior characteristic of a weak viscoelastic gel with the elastic modulus dominant over the viscous modulus. Reduced and proteolytically digested mucus has the behavior of viscous liquid where the viscous modulus is dominant over the loss modulus for much of the frequency range accessed.



Figure 1.

A: adherent gastric mucus viewed under bright field on a transverse section 1.6 mm thick) of rat gastric mucosa. Three distinct phases can be seen clearly: mucosa, mucus gel layer, and bathing solution. For method, see Kerss et al. 111. B: reepithelialized mucosa: rat gastric mucosa after exposure to 70% (vol/vol) ethanol for 45 s and rapid wash with 0.9% (wt/vol) sodium chloride followed by 0.9% (wt/vol) sodium chloride for 1 h. Mucosa was formalin fixed, embedded in paraffin wax, and sections were stained with periodic acid‐Schiff stain for mucin.

A courtesy of L. A. Sellers; B from Sellers et al. 209


Figure 2.

Diagram of a subunit of mucus glycoprotein structure showing glycosylated “bottle brush” and nonglycosylated regions. Subunits are joined by disulfide bridges to form overall linear polymeric mucins. Detailed tertiary structure of subunits within the polymeric mucin has not been elucidated.



Figure 3.

Composite diagram of proposed structures for typical branched oligosaccharides in human 223 and pig 219 gastric mucin glycoproteins showing the immunodeterminant blood group A and H (— — —) and I (‐ ‐ ‐) saccharide structures. Location of sulfate esters on the chains is not known. Fuc, fucose; Gal, galactose; GalNAc, N‐acetylgalactosamine; GlcNAc, N‐acetylglucosamine.



Figure 4.

Physical properties of pig gastric mucus in dilute solution (A) and in native mucus gel (B). A: dependence of solution viscosity of pig gastric mucus on glycoprotein concentration. Viscosity of the solution rises asymptotically with increased glycoprotein concentration until it assumes the properties of a gel at a glycoprotein concentration of ∼50 mg/ml 14,20. This can be explained by the large hydrated glycoprotein molecules at higher concentrations occupying the whole solution volume and their overlapping molecular domains interacting noncovalently to form the mucus‐gel matrix. Concentration of glycoprotein in gastric mucus (pig and human) is ∼50 mg/ml. Reduced or proteolytically degraded glycoprotein subunits have a low solution viscosity and do not form gel at high concentrations of glycoprotein. B: mechanical spectrum for pig gastric mucus showing a plot of elastic (storage modulus, —–) and viscous (loss modulus, —–) moduli against frequency of oscillatory deformations 20. Mucus gel is sandwiched between a flat plate and shallow cone and subjected to small deformations at different oscillatory frequencies without disrupting gel structure. From the magnitude and phase of stress generated in resistance to applied deformation the storage modulus G’ (elastic or solid component) and the loss modulus G” (viscous or liquid component) can be calculated. Native gastric mucus and mucus reconstituted from isolated glycoprotein have the behavior characteristic of a weak viscoelastic gel with the elastic modulus dominant over the viscous modulus. Reduced and proteolytically digested mucus has the behavior of viscous liquid where the viscous modulus is dominant over the loss modulus for much of the frequency range accessed.

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Adrian Allen. Gastrointestinal Mucus. Compr Physiol 2011, Supplement 18: Handbook of Physiology, The Gastrointestinal System, Salivary, Gastric, Pancreatic, and Hepatobiliary Secretion: 359-382. First published in print 1989. doi: 10.1002/cphy.cp060319