Duodenal Regulation (Enteric Inhibition)
The inhibition process is closely linked to the movement of food into the small intestine. When chyme enters the duodenum, its receptors respond to increased acidity and the presence of nutrient breakdown products. In response, endocrine cells in the intestinal mucosa release specific hormones into the bloodstream—secretin and cholecystokinin (CCK).
These substances exert a dissociated (divergent) effect on gastric glands:
- Inhibit the activity of parietal cells, sharply reducing hydrochloric acid production.
- Stimulate chief cells, enhancing the secretion of the enzyme pepsinogen.
Furthermore, if the environment in the duodenum becomes excessively acidic, hydrochloric acid secretion is inhibited simultaneously via two pathways: through the release of duodenal hormones and via reflex neural influences.
Humoral Inhibitors of Secretion
In addition to secretin and cholecystokinin, a wide range of substances in the body can suppress gastric gland activity. These humoral factors are delivered to target cells via the bloodstream and include the following compounds:
- Intestinal and pancreatic peptides: glucagon, gastric inhibitory peptide (GIP), vasoactive intestinal peptide (VIP), neurotensin.
- Tissue hormones and mediators: serotonin, somatostatin, gastrones (including bulbogastrone and cologastrone).
- Pituitary and thyroid hormones: vasopressin (antidiuretic hormone), oxytocin, thyrotropin-releasing hormone, calcitonin.
- Prostaglandins: specifically $PGE_2$, which not only suppresses acid production but also plays a key role in cytoprotection.
These substances provide fine-tuning of the digestive process, preventing the excessive secretion of aggressive gastric juice.
Autoregulation Mechanisms and Receptor Apparatus
Hydrochloric acid production is controlled by a strict negative feedback mechanism. The primary endogenous stimulant is the hormone gastrin, which is synthesized by G-cells located predominantly in the mucosa of the pyloric (antral) part of the stomach.
Gastrin release depends on the acidity level (pH-dependent autoregulation):
- When the antral pH drops to 3.0, gastrin secretion begins to be inhibited.
- If the pH drops to 1.0, hormone release stops completely, leading to a sharp decrease in glandular activity.
Clinical significance: surgical removal of the pyloric region deprives the body of the main pool of G-cells, resulting in a radical and persistent decrease in gastric secretion.
An important role in paracrine control is played by histamine, released by mast cells. It acts on $H_2$ receptors of parietal cells, inducing the secretion of acidic juice that is low in enzymes. Interestingly, high doses of histamine can exert an inhibitory effect on pepsinogen production by chief cells.
Protection of the Gastric Mucosa
The inhibition of aggressive factors always works in tandem with protective mechanisms. The gastric mucosa is protected from digestion by its own enzymes and acid through a robust barrier. This barrier consists primarily of insoluble mucus and bicarbonate ions ($HCO_3^-$), which create a neutralizing layer on the epithelial surface.
Key stimulators of bicarbonate and mucus production are prostaglandins ($PGE_2$ and $PGI_2$).
In clinical practice, this physiological mechanism is frequently disrupted by the use of nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs inhibit the enzyme cyclooxygenase-1 (COX-1), leading to a drop in prostaglandin levels. As a result, the protective bicarbonate-mucus barrier thins, acid secretion increases, and conditions favorable for ulcer formation are created.