Parietal cells secrete HCl via the H+/K+-ATPase (proton pump) on the apical canalicular membrane. Three converging stimuli ramp the pump's activity: histamine (H2R, Gs → cAMP), acetylcholine (M3R, Gq → IP3 → Ca²⁺), gastrin (CCK2R, Gq). PPIs (omeprazole, pantoprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole) are acid-activated prodrugs that covalently inactivate the proton pump cysteine; effect outlasts plasma exposure. H2 blockers (famotidine, ranitidine — withdrawn 2020 for NDMA contamination, but slug retained) compete at H2R. M3 antagonists no longer used (broad anticholinergic side effects). Misoprostol is a PGE1 analog → mucosal cytoprotection + acid suppression; abortifacient at higher doses.
Organ Systems
digestive
Pathway Steps
parietal-cell-stimulation → h-k-atpase-activation — via histamine-H2/Gs, ACh-M3/Gq, gastrin-CCK2/Gq converge on apical pump. Three stimuli converge on the parietal cell: histamine (H2/Gs from ECL cells — the dominant amplifier), acetylcholine (M3/Gq, vagal), and gastrin (CCK2/Gq). This is why H2-blockers and vagotomy reduce acid; somatostatin is the physiologic brake.
h-k-atpase-activation → gastric-hcl-secretion — via H+ pumped into lumen → 1-4 M HCl in cannaliculi. The H⁺/K⁺-ATPase (proton pump) is the final common step, secreting H⁺ to make luminal HCl as low as ~pH 1. It is the irreversible target of proton-pump inhibitors, which bind only the activated pump — hence PPIs work best dosed before meals.