The stomach contains tetrameric mucins that create a sticky gel, which adheres to the stomach surface. Pepsins, enzymes that cleave disulfide bonds in the center of the tetramers, can break down this gel. When proteolysis occurs, fragments are released that cannot form gels, resulting in the dissolution of the protective mucous layer. To maintain this protective layer, new tetrameric mucins need to be continuously synthesized to replace the ones cleaved by pepsins.

Mucus is secreted at a significant rate in the stomach when it is at rest. The secretion of mucus is stimulated by the same factors that enhance the secretion of acid and pepsinogen, especially acetylcholine released from parasympathetic nerve endings near the gastric glands. Mechanical deformation of the gastric mucosa triggers neural reflexes that increase mucus secretion.

The regulation of gastric secretion is primarily influenced by parasympathetic innervation through the vagus nerve. Extrinsic efferent fibers connect with intrinsic neurons that innervate parietal cells, ECL cells responsible for histamine secretion, and endocrine cells that secrete gastrin. Vagal stimulation also leads to the secretion of pepsinogen, mucus, HCO3−, and intrinsic factor. While parasympathetic nervous system stimulation occurs during the cephalic and oral phases of a meal, the gastric phase produces the greatest stimulation of gastric secretion in the postprandial period.

The stimulation of gastric acid secretion is an example of a "feed-forward" response involving endocrine, paracrine, and neural pathways. Vagal efferent activity activates intrinsic neurons, leading to the release of various substances.

The structure of gastric mucins consists of a protein core that is protected from further proteolysis, a glycosylated part composed of carbohydrate chains attached to peptide cores (which are resistant to proteolysis), and a nonglycosylated part composed of peptide cores connected by disulfide bridges (which are the site of proteolysis). Before hydrolysis by pepsin, intact mucins are tetramers formed by four similar monomers weighing approximately 500,000 Da. The majority of each monomer is covered by carbohydrate side chains, which shield it from proteolytic degradation. The central portion of the mucin tetramer, near the disulfide cross-links, is more susceptible to proteolytic digestion. Pepsins cleave bonds near the center of the tetramers, releasing fragments of a similar size to monomers.
These tetrameric mucins form a sticky gel that adheres to the surface of the stomach. This gel is subject to proteolysis by pepsins that cleave disulfide bonds near the center of the tetramers. Proteolysis releases fragments that do not form gels and thus dissolves the protective mucous layer. Maintenance of the protective mucous layer requires continuous synthesis of new tetrameric mucins to replace the mucins cleaved by pepsins.
Mucus is secreted at a significant rate in the resting stomach. Secretion of mucus is stimulated by some of the same stimuli that enhance acid and pepsinogen secretion, especially acetylcholine released from parasympathetic nerve endings near the gastric glands. If the gastric mucosa is mechanically deformed, neural reflexes are evoked to enhance mucus secretion.
Regulation of Gastric Secretion
Parasympathetic innervation via the vagus nerve is the strongest stimulant of gastric H+ secretion. Extrinsic efferent fibers terminate on intrinsic neurons that innervate parietal cells, ECL cells that secrete the paracrine mediator histamine, and endocrine cells that secrete the hormone gastrin. In addition, vagal stimulation results in secretion of pepsinogen, mucus, HCO3 − , and intrinsic factor. Stimulation of the parasympathetic nervous system also occurs during the cephalic and oral phase of the meal. However, the gastric phase produces the largest stimulation of gastric secretion of the postprandial period (
Fig. 29.6
Stimulation of gastric acid secretion is an excellent example of a “feed-forward” (or cascade) response that uses endocrine, paracrine, and neural pathways. Activation of intrinsic neurons by vagal efferent activity results in release
Protein core: protected from further proteolysisGlycosylated part of by carbohydrate chains peptide cores (resistant to
Sheath of branched proteolysis) carbohydrate chains with average of 15 Nonglycosylated part of sugars per chain peptide cores with disulfide bridges joining subunits (site of proteolysis) • Fig.29.5Schematic representation of the structure of gastric mucins before and after hydrolysis by pepsin. Intact mucins are tetramers of four similar monomers of about 500,000 Da. Each monomer is largely covered by carbohydrate side chains that protect it from proteolytic degradation. The central portion of the mucin tetramer, near the disulfide cross-links, is more susceptible to proteolytic digestion. Pepsins cleave bonds near the center of the tetramers to release fragments about the size of monomers.