Regulation of Acid Secretion

Introduction

Parietal cells in the stomach secrete roughly two liters of acid a day in the form of hydrochloric acid. Acid in the stomach functions to kill bacteria, and to aid digestion by solubilizing food. The acid is also important to establish the optimal pH (between 1.8-3.5) for the function of the digestive enzyme pepsin.

A key protein for acid secretion is the H+/K+-ATPase (or proton pump). This protein, which is expressed on the apical membrane of parietal cells, uses the energy derived from ATP hydrolysis to pump hydrogen ions into the lumen in exchange for potassium ions.

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Stimulation of acid secretion involves the translocation of H+/K+-ATPases to the apical membrane of the parietal cell. When the cell is resting (not stimulated), H+/K+-ATPases are located in vesicles inside the cell. When the cell is stimulated, these vesicles fuse with the plasma membrane, thereby increasing the surface area of the plasma membrane and the number of proton pumps in the membrane.


acid-2.pngThere are three regulatory molecules that stimulate acid secretion (acetylcholine, histamine, gastrin) and one regulatory molecule that inhibits acid secretion (somatostatin). Acetylcholine is a neurotransmitter that is released by enteric neurons. Histamine is a paracrine that is released from ECL (enterochromaffin-like) cells. Gastrin is a hormone that is released by G cells, endocrine cells that are located in the gastric epithelium. Somatostatin is also secreted by endocrine cells of the gastric epithelium; it can act as either a paracrine or a hormone.

The figure (same as on the handout) shows how the positive and negative regulators interact to stimulate acid secretion. Acetylcholine and histamine directly stimulate parietal cells to increase acid secretion. Gastrin stimulates acid secretion by stimulating histamine release from ECL cells. (Gastrin also has a direct effect on parietal cells, which is to stimulate their proliferation).  When the pH of the stomach gets too low, somatostatin secretion is stimulated. Somatostatin inhibits acid secretion by direct effects on parietal cells, and also by inhibiting release of the positive regulators histamine and gastrin.  The balance of activity of the different regulators changes as food is consumed and passes through different segments of the upper GI tract.




Cephalic Phase

Cephalic phase stimuli are things like the sight, smell, taste or thought of food. These stimuli, processed by the brain, activate enteric neurons via parasympathetic preganglionic neurons traveling in the vagus nerve. ceph.jpg
  (Click on image to see figure in a new window.)

Gastric Phase

The primary factor during the gastric phase is that there is food in the stomach, which stimulates acid secretion. There are three different ways that this occurs. Food will stretch the walls of the stomach; this is sensed by mechanoreceptors, activating a neural reflex to stimulate acid secretion (purple). Peptides and amino acids in food stimulate G cells to release gastrin (blue). Food also acts as a buffer, raising the pH and thus removing the stimulus for somatostatin secretion (light blue-green). gast.jpg
  (Click on image to see figure in a new window.)

Intestinal Phase

Once chyme enters the duodenum, intestinal phase stimuli activate negative feedback mechanisms to reduce acid secretion and prevent the chyme from becoming too acidic. This occurs by neural reflexes and hormonal reflexes. Enterogastrones are hormones that inhibit stomach processes (in this case, acid secretion). In addition to their other actions, CCK, secretin, GLP-1, and GIP act as enterogastrones. intest.jpg
  (Click on image to see figure in a new window.)