Acetylcholine, gastrin and histamine all converge on the proton pump
Expansion
Three stimulatory receptors on the parietal cell:
- Muscarinic M3 - acetylcholine from the vagus
- CCK-B (gastrin) receptor - gastrin
- H2 receptor - histamine from enterochromaffin-like cells
The first two act through calcium, the third through cyclic AMP. Histamine also potentiates the other two, which is why H2 blockers reduce acid secretion even from vagal and gastrin stimulation.
All converge on the hydrogen-potassium ATPase (proton pump) on the apical membrane, which exchanges hydrogen for potassium and generates a luminal pH as low as 1, a millionfold gradient.
Inhibited by somatostatin and prostaglandin E2, both acting through reduced cyclic AMP. This is why NSAIDs, by blocking prostaglandin synthesis, remove a protective brake as well as impairing mucus and bicarbonate secretion.
For every hydrogen ion secreted, a bicarbonate ion enters the blood, producing the postprandial alkaline tide, and explaining the metabolic alkalosis of prolonged vomiting.