Somatostatin Primarily Inhibits Gastrin Release from Antral G Cells
Somatostatin (option 4) is the primary physiological inhibitor of gastrin release from G cells in the gastric antrum. This inhibition occurs through direct paracrine effects via somatostatin receptor subtype 2 (sst2) activation on gastrin cells 1.
Mechanism of Somatostatin Inhibition
Somatostatin exerts its inhibitory effect through multiple levels of regulation:
Direct paracrine action: Somatostatin-producing D cells are located in close anatomical proximity to gastrin-producing G cells in the antral mucosa, allowing local regulatory control 2.
Pretranslational inhibition: Somatostatin suppresses gastrin gene transcription by 33.8% and reduces steady-state gastrin mRNA levels in a dose-dependent manner 2.
Post-translational effects: Beyond gene expression, somatostatin directly inhibits gastrin peptide release from G cells 3.
Receptor-mediated mechanism: The inhibitory effect is specifically mediated through sst2 receptors on gastrin cells, as demonstrated by selective sst2 agonists (like EC 5-20) that reproduce somatostatin's inhibitory effects 1.
Evidence for Somatostatin's Physiological Role
The physiological importance of somatostatin is demonstrated by antibody neutralization studies:
When endogenous somatostatin is neutralized with specific antibodies, gastrin mRNA levels increase by 116% over baseline 2.
Somatostatin antibodies completely abolish acid-induced inhibition of gastrin secretion, proving that somatostatin is an essential paracrine link in this regulatory pathway 4.
This tonic inhibitory influence operates continuously under basal conditions 1.
Why Other Options Are Incorrect
Vagal efferent activation (option 1) stimulates rather than inhibits gastrin release:
Vagal stimulation increases both gastrin and somatostatin secretion simultaneously 4.
The cholinergic pathway actually inhibits somatostatin release, thereby indirectly stimulating gastrin 3.
Circulating epinephrine (option 2) is not a primary regulator:
- No evidence supports epinephrine as a physiological inhibitor of gastrin release from the provided literature.
Blood-borne calcium (option 3) stimulates rather than inhibits:
- Calcium is known to stimulate gastrin release, not inhibit it, based on general physiological principles.
Clinical Relevance
This mechanism has direct therapeutic applications:
Somatostatin analogues (octreotide, lanreotide) are used clinically to inhibit gastrin secretion in gastrinomas and other neuroendocrine tumors 5, 6.
These analogues bind primarily to sst2 receptors with high affinity, reproducing the physiological inhibitory effect 5.
The effectiveness of somatostatin analogues in controlling gastric acid hypersecretion validates the physiological importance of this regulatory pathway 5.
Acid-Somatostatin-Gastrin Feedback Loop
Gastric acid provides negative feedback through somatostatin:
Luminal acidification increases somatostatin output 9-fold while inhibiting gastrin secretion to 61% of baseline 4.
This acid-induced somatostatin release is a direct effect on D cells, unaffected by neural blockade with tetrodotoxin 3.
Neutralizing somatostatin with antibodies completely eliminates acid's inhibitory effect on gastrin, confirming somatostatin as the essential mediator 4.