Gastrin-releasing peptide (GRP) is a messenger molecule used by the body’s nervous and digestive systems. This neuropeptide is the human equivalent of bombesin, a substance first identified in amphibian skin. GRP is produced in the gastrointestinal tract and central nervous system, allowing it to participate in a wide range of bodily functions.
The peptide is formed from a larger precursor molecule called a preproprotein. This initial chain is processed and cut to create the final, active 27-amino-acid GRP molecule. This production occurs in specific nerve cells, allowing GRP to act as a targeted signal for nearby cells with the correct receptor.
The Role of GRP in Digestion
In the digestive system, gastrin-releasing peptide is a primary regulator of stomach acid secretion. When food enters the stomach, it triggers nerve endings of the vagus nerve in the stomach wall. These nerve endings release GRP, which then travels to specialized endocrine cells known as G-cells.
The arrival of GRP at the G-cells acts as a direct signal, causing them to secrete a hormone called gastrin into the bloodstream. Gastrin circulates and binds to another group of stomach cells, the parietal cells. This binding instructs the parietal cells to begin pumping hydrochloric acid into the stomach.
The resulting acidic environment, with a pH between 1.5 and 3.5, chemically breaks down complex proteins. This acidity also serves a protective function by destroying most bacteria and viruses ingested with food, reducing the risk of gastrointestinal infections.
Beyond acid secretion, GRP influences other digestive processes. It stimulates chief cells in the stomach to release pepsinogen, which becomes the active enzyme pepsin in acidic conditions. GRP also affects the smooth muscle contractions that churn and mix stomach contents.
GRP Functions in the Nervous System
Within the nervous system, gastrin-releasing peptide functions as a neurotransmitter with diverse roles. One of its most understood functions is in the sensation of itch. When an irritant affects the skin, specific nerves send a signal to the spinal cord, where GRP is released. It acts as a dedicated messenger for itch, transmitting the sensation to the brain without activating pain pathways.
GRP also plays a part in regulating appetite and feelings of fullness. After a meal, GRP is released in the brain, signaling the hypothalamus that the body has received sufficient nutrients. This contributes to the sensation of being full, which helps control food intake and prevent overeating.
The peptide is involved in the brain’s response to fear and the formation of related memories. Within the amygdala, a brain region for emotional processing, GRP modulates neural circuits. Its activity can influence fear conditioning, where the brain learns to associate a stimulus with a negative outcome, and contributes to anxiety-related behaviors.
GRP contributes to maintaining the body’s internal 24-hour clock, or circadian rhythm. It is found in the suprachiasmatic nucleus of the hypothalamus, the body’s master timekeeper. Here, GRP helps relay information about light from the eyes, assisting in synchronizing the internal clock with the external day-night cycle.
Clinical Significance and Medical Applications
The properties of gastrin-releasing peptide and its receptor (GRPR) have implications in oncology. Many cancer cells, including those in small-cell lung, prostate, breast, and colon cancers, express an abnormally high number of GRP receptors. This overexpression provides a target for both diagnosing and treating these diseases.
Scientists leverage this by creating synthetic molecules that mimic GRP and bind to its receptors. For imaging, a radioactive tracer is attached to these molecules. When injected, they accumulate on tumors, allowing them to be visualized on positron emission tomography (PET) scans to locate tumors and monitor treatment.
A similar strategy is used for treatment in peptide receptor radionuclide therapy (PRRT). Instead of a tracer, a powerful, cell-killing radioactive particle is attached to the GRP-mimicking molecule. This compound delivers a high dose of radiation directly to the tumor while largely sparing surrounding healthy tissues.