Gastrin is a peptide hormone that acts as a chemical messenger within the digestive system. It is produced primarily by specialized cells called G-cells, which are located predominantly in the lining of the stomach’s lower section, known as the gastric antrum. Once released into the bloodstream, gastrin travels to other parts of the stomach to prepare the organ for food digestion. By signaling the stomach to begin its major work, gastrin plays a central part in breaking down nutrients.
The Primary Role of Gastrin in Digestion
Gastrin’s main function is to trigger the secretion of hydrochloric acid (HCl) by the parietal cells, which are situated in the stomach’s upper body and fundus. Gastrin achieves this by directly binding to parietal cell receptors and by stimulating enterochromaffin-like (ECL) cells to release histamine. This histamine then acts locally to intensify acid production. The resulting highly acidic environment is necessary for breaking down food structures and activating digestive enzymes.
The strong acid environment causes proteins to unfold, a process called denaturation, making them more susceptible to enzymatic action. The acid also converts inactive pepsinogen, which is secreted by chief cells, into its active form, pepsin. Pepsin is an enzyme that begins the chemical digestion of proteins into smaller peptide fragments.
Beyond its secretory role, gastrin also acts as a trophic, or growth-promoting, hormone for the stomach lining. It stimulates the maturation and proliferation of the gastric mucosal cells, helping to maintain the health and thickness of the stomach wall. This trophic effect is particularly pronounced on the parietal and ECL cells. Gastrin also increases gastric motility, which helps to mix the food with the digestive juices and ensures the contents move efficiently into the small intestine.
Regulation of Gastrin Production
Gastrin secretion is controlled through neurological and hormonal signals corresponding to the three phases of digestion. The cephalic phase begins before food enters the stomach, initiated by the sight, smell, taste, or thought of food. This phase uses the vagus nerve to signal the G-cells to release a small amount of gastrin, preparing the stomach for the meal.
The most significant release of gastrin occurs during the gastric phase, activated once food is physically present in the stomach. The stomach wall distending from the meal and the presence of partially digested proteins, especially amino acids, directly trigger the G-cells to secrete large amounts of gastrin. This creates a positive feedback loop where increased protein breakdown leads to more gastrin and more acid, accelerating digestion.
Gastrin release is controlled by a negative feedback mechanism designed to prevent excessive acid production. When the stomach acid concentration becomes too high, dropping the pH below approximately 3, it signals a regulatory shift. This low pH stimulates D-cells in the stomach lining to release somatostatin, a hormone that inhibits the G-cells. This ensures that once the food is adequately processed, the gastric acid output is downregulated, protecting the stomach lining.
Understanding Gastrin Imbalances
An imbalance in gastrin levels, either too high or too low, can lead to digestive problems. Hypergastrinemia, or excess gastrin in the blood, most commonly results from Zollinger-Ellison Syndrome (ZES). This rare disorder is caused by a gastrinoma, a neuroendocrine tumor that secretes gastrin uncontrollably, regardless of the body’s regulatory signals.
The constant, excessive gastrin stimulation in ZES leads to overproduction of stomach acid, resulting in peptic ulcers that may form in unusual locations like the small intestine. The volume of acid can also overwhelm the small intestine, inactivating pancreatic enzymes and bile salts. This leads to chronic diarrhea and malabsorption of nutrients. The trophic effect of the excess gastrin can also cause the stomach lining to thicken and its cells to multiply.
Hypergastrinemia can also occur when acid levels are low, such as in atrophic gastritis or pernicious anemia. In these cases, the acid-producing cells are damaged, leading to a high stomach pH, which removes the normal low-pH inhibitory signal on the G-cells. The G-cells then attempt to compensate for the lack of acid by continuously secreting gastrin, driving up blood levels.
A functional deficiency, or insufficient gastrin activity, can lead to low stomach acid, known as hypochlorhydria. Without adequate gastrin stimulation, the stomach fails to produce enough HCl to maintain a properly acidic environment. This impaired acid production compromises the initial steps of protein digestion and prevents the activation of pepsin. The stomach’s reduced ability to kill ingested microbes can also increase the risk of intestinal infections, as the body’s natural sterile barrier is weakened.