Chief CellEdit
Chief cell
Chief cells are specialized exocrine cells of the stomach lining, best known for their role in initiating protein digestion. Located in the bases of the gastric glands, particularly within the fundic glands of the stomach body, these cells secrete pepsinogen, a zymogen that is activated to the proteolytic enzyme pepsin in the acidic environment of the stomach. In addition to pepsinogen, some chief cells contribute small amounts of other secretions such as gastric lipase, a digestive enzyme that aids fat digestion. The efficiency of protein digestion depends on the timely release of pepsinogen and its conversion to pepsin, a process tightly integrated with stomach acidity and neural-hormonal signaling.
Habitual arrangement and appearance
Chief cells occupy the deeper portions of the gastric glands, lying below the parietal cells that secrete gastric acid. Their cytoplasm is typically basophilic, reflecting a high content of rough endoplasmic reticulum involved in protein synthesis. They store secretory granules containing pepsinogen near the apical region of the cell, ready for regulated exocytosis into the glandular lumen. The histological appearance—a basophilic cytoplasm with apically located secretory granules—helps distinguish chief cells from neighboring cell types such as parietal cells and mucous cells within the same gland.
Biochemistry of secretion
The primary product of chief cells is pepsinogen. Upon release into the stomach lumen, pepsinogen encounters the acidic milieu generated mainly by parietal cells, which secrete hydrochloric acid via proton pumps and chloride channels. The low pH catalyzes the conversion of pepsinogen to pepsin, the active protease that begins the breakdown of dietary proteins into peptides. Gastric lipase, another enzyme present in the gastric milieu, contributes modestly to fat digestion in conjunction with bile salts later in the digestive tract. Pepsin remains active in a pH range typical of the stomach and becomes inactivated as chyme moves into the more neutral duodenum.
Regulation of secretion
Chief cell activity is governed by a combination of neural and hormonal signals. Acetylcholine, released from vagal nerve endings during cephalic phase and gastric stimulation, promotes exocytosis of pepsinogen-containing granules. Gastrin, produced by G cells in the antral mucosa, has a direct stimulatory effect on chief cells, increasing pepsinogen secretion in addition to its well-known actions on parietal and enterochromaffin-like cells. Histamine, acting primarily through H2 receptors on parietal and other glandular cells, supports an integrated secretory response that amplifies digestive secretions overall. The coordinated release of pepsinogen with acid ensures efficient initiation of protein digestion at the earliest stage of processing in the stomach.
Clinical and physiological significance
Understanding chief cells clarifies how the stomach prepares proteins for digestion. Disruptions to the regulation of chief cells—whether from altered neural input, hormonal signaling, or mucosal pathology—can impact the efficiency of protein breakdown. In some conditions, the gastric mucosa undergoes adaptive changes that affect the distribution or activity of chief cells, with downstream effects on digestion. The peptides generated by pepsin activity further influence downstream digestive processes in the small intestine, where brush-border enzymes and pancreatic proteases complete protein digestion.
See also