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.