The HCl present in the gastric lumen is secreted by the parietal cells of the corpus and fundus. The mechanism of HCl production is depicted in Figure 27.6. An H+/K+-ATPase in the apical (luminal) cell membrane of the parietal cell actively pumps H+ out of the cell in exchange for
Plasma Parietal cell Lumen
Plasma Parietal cell Lumen
K+ entering the cell. The H+/K+-ATPase is inhibited by omeprazole. Omeprazole, an acid-activated prodrug that is converted in the stomach to the active drug, binds to two cysteines on the ATPase, resulting in an irreversible inacti-vation. Although the secreted H+ is often depicted as being derived from carbonic acid (see Fig. 27.6), the source of H+ is probably mostly from the dissociation of H2O. Carbonic acid (H2CO3) is formed from carbon dioxide (CO2) and H2O in a reaction catalyzed by carbonic anhydrase. Carbonic anhydrase is inhibited by acetazolamide. The CO2 is provided by metabolic sources inside the cell and from the blood.
For the H+/K.+ -ATPase to work, an adequate supply of K.+ ions must exist outside the cell. Although the mechanism is still unclear, there is an increase in K+ conductance (through K+ channels) in the apical membrane of the parietal cells simultaneous with active acid secretion. This surge of K+ conductance ensures plenty of K+ in the lumen. The H+/K+-ATPase recycles K+ ions back into the cell in exchange for H+ ions. As shown in Figure 27.6, the basolateral cell membrane has an electroneutral Cl~/HCO3~ exchanger that balances the entry of Cl_ into the cell with an equal amount of HCO3~ entering the bloodstream. The Cl_ inside the cell then leaks into the lumen through Cl" channels, down an electrochemical gradient. Consequently, HCl is secreted into the lumen.
A large amount of HCl can be secreted by the parietal cells. This is balanced by an equal amount of HCO3~ added to the bloodstream. The blood coming from the stomach during active acid secretion contains much HCO 3 , a phenomenon called the alkaline tide. The osmotic gradient created by the HCl concentration in the gland lumen drives water passively into the lumen, thereby, maintaining the iso-osmolality of the gastric secretion.
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