From the Guidelines
Gastric acid secretion is primarily regulated by a complex interplay of hormones and neural pathways, with the most critical factor being the balance between stimulatory and inhibitory signals to prevent excessive acid production and maintain mucosal integrity. The process involves three phases: cephalic, gastric, and intestinal, each contributing to the regulation of acid secretion 1.
Key Regulatory Mechanisms
- The cephalic phase is initiated by the sight, smell, taste, or thought of food, triggering the vagus nerve to stimulate parietal cells directly and indirectly through gastrin-releasing cells.
- The gastric phase involves proteins stimulating G cells to release gastrin, which promotes acid secretion, and distension of the stomach activating local neural reflexes to enhance acid production.
- The intestinal phase provides negative feedback when acidic chyme enters the duodenum, involving hormones like secretin and cholecystokinin to suppress acid secretion.
Hormonal Regulation
- Gastrin stimulates acid secretion and promotes the proliferation of parietal cells, as seen in the context of rebound acid hypersecretion after discontinuation of proton pump inhibitors (PPIs) 1.
- Histamine, released from enterochromaffin-like (ECL) cells, acts as a powerful secretagogue on parietal cells via H2 receptors.
- Somatostatin inhibits both gastrin release and parietal cell function, playing a crucial role in limiting acid production.
Neural Pathways
- The vagus nerve directly stimulates parietal cells and indirectly through gastrin-releasing cells, with acetylcholine being a key neurotransmitter.
- The enteric nervous system and central connections via the vagus nerve regulate acid secretion, with neurotransmitters like vasoactive intestinal peptide (VIP) inhibiting acid production.
Clinical Implications
Understanding the regulation of gastric acid secretion is crucial for managing conditions like gastroesophageal reflux disease (GERD) and peptic ulcer disease, where the balance between acid production and mucosal defense is disrupted. The recent evidence on rebound acid hypersecretion after PPI discontinuation 1 highlights the importance of careful management and potential gradual tapering of PPI therapy to minimize symptoms and prevent complications.
From the FDA Drug Label
- Clinical Pharmacology 12. 1 Mechanism of Action Omeprazole belongs to a class of antisecretory compounds, the substituted benzimidazoles, that suppress gastric acid secretion by specific inhibition of the H+/K+ ATPase enzyme system at the secretory surface of the gastric parietal cell
- The regulation of gastric acid secretion is not directly described in terms of hormones and neural pathways in the provided text.
- The text only mentions that omeprazole inhibits both basal and stimulated acid secretion, but it does not specify the role of hormones and neural pathways in this process.
- Therefore, the information provided does not directly answer the question about the regulation of gastric acid secretion, including the role of hormones and neural pathways. The FDA drug label does not answer the question.
From the Research
Regulation of Gastric Acid Secretion
The regulation of gastric acid secretion is a complex process involving various central and peripheral pathways, including neural, hormonal, and paracrine mechanisms 2. These pathways regulate the acid-producing parietal cell directly and/or indirectly by regulating the secretion of histamine from enterochromaffin-like cells, gastrin from G cells, and somatostatin from D cells.
Role of Hormones
Several hormones play a crucial role in regulating gastric acid secretion, including:
- Gastrin: stimulates acid secretion and is also a trophic hormone that participates in carcinogenesis 3
- Histamine: stimulates the parietal cell directly via H(2) receptors and indirectly via H(3) receptors coupled to inhibition of somatostatin secretion 4
- Somatostatin: exerts a tonic restraint on parietal, enterochromaffin-like (ECL), and gastrin cells, inhibiting acid secretion 4
- Ghrelin: stimulates acid secretion 5
- Cholecystokinin: inhibits acid secretion 5
- Glucagon-like peptide-1: inhibits acid secretion 5
- Atrial natriuretic peptide: inhibits acid secretion 5
Neural Pathway
The neural pathway also plays a significant role in regulating gastric acid secretion, with:
- Acetylcholine: released from gastric postganglionic intramural neurons, stimulates the parietal cell directly via muscarinic M(3) receptors and indirectly by inhibiting somatostatin secretion 4
- Pituitary adenylate cyclase-activating polypeptide: stimulates histamine secretion from isolated ECL cells, but its physiologic role is not known 4
Physiologic and Pathophysiologic Regulation
Gastric acid secretion is physiologically regulated to facilitate digestion, absorption of nutrients, and killing of microorganisms 3. However, pathophysiologic regulation can lead to disorders such as gastroesophageal reflux disease, autoimmune gastritis, gastric cancer, and functional dyspepsia 6. The use of proton pump inhibitors can also affect gastric acid secretion, with concerns raised regarding dysbiosis, atrophic gastritis, hypergastrinemia, hypomagnesemia, and enteritis/colitis 5.