Pepsin and Hydrochloric Acid Secretion

The parietal cells secrete H+, at a pH as low as 0.8, into the gastric lumen by primary active transport (involving carriers that function as an ATPase). These carriers, known as H+/K+ ATPase pumps, transport H+ uphill against a million-to-one concentration gradient into the lumen of the stomach while they transport K+ in the opposite direction (fig. 18.8).

At the same time, the parietal cell's basolateral membrane (facing the blood in capillaries of the lamina propria) take in Cl-against its electrochemical gradient by coupling its transport to

■ Figure 18.7 Gastric pits and gastric glands of the mucosa.

(a) Gastric pits are the openings of the gastric glands. (b) Gastric glands consist of several types of cells (including mucous cells, chief cells, and parietal cells), each of which produces a specific secretion.

the downhill movement of bicarbonate (HCO3-). The bicarbonate ion is produced within the parietal cell by the dissociation of carbonic acid, formed from CO2 and H2O by the enzyme carbonic anhydrase. Therefore, the parietal cell can secrete Cl- (by facilitative diffusion) as well as H+ into the gastric juice while it secretes bicarbonate into the blood (fig. 18.8).

The secretion of HCl by the parietal cells is stimulated by a variety of factors, including the hormone gastrin, secreted by the G cells, and acetylcholine (ACh), released by axons of the vagus nerve. Most of the effects of gastrin and ACh on acid secretion, however, are currently believed to be indirect. Gastrin and ACh from vagal axons stimulate the release of his-tamine from the ECL cells of the gastric mucosa, and hista-mine, in turn, acts as a paracrine regulator to stimulate the parietal cells to secrete HCl (see fig. 18.30). The endocrine regulation of the digestive system is discussed in detail later in this chapter.

People with gastroesophageal reflux disease, a common disorder involving the reflux of acidic gastric juice into the esophagus, are often treated with specific drugs (including Prilosec and Prevacid) that inhibit the K+/H+ pumps in the gastric mucosa. Since gastric acid secretion is stimulated by histamine released from the ECL cells, people with peptic ulcers can be treated with drugs that block histamine action. Drugs in this category, such as Tagamet and Zantac, specifically block the H2 histamine receptors in the gastric mucosa. This is a different receptor subtype than that blocked by antihistamines commonly used to treat cold and allergy symptoms.

The only stomach function that appears to be essential ■J for life is the secretion of intrinsic factor. This polypep-

n___ | ^ tide is needed for the absorption of vitamin B12 in the terminal portion of the ileum in the small intestine, and vitamin B|2 is required for maturation of red blood cells in the bone marrow. Following surgical removal of the stomach (gastrectomy), a patient has to receive B|2 injections or take B|2 orally, together with intrinsic factor. Without vitamin B|2, pernicious anemia will develop.

© The McGraw-Hill Companies, 2003

The Digestive System

Facilitative diffusion

Lumen of stomach

Facilitative diffusion

Primary active transport

(ATPase carrier)

Primary active transport

(ATPase carrier)

Parietal cell -



Secondary active transport HCO

Blood capillaries

■ Figure 18.8 Secretion of gastric acid by parietal cells. The apical membrane (facing the lumen) secretes H+ in exchange for K+ using a primary active transport carrier that is powered by the hydrolysis of ATP. The basolateral membrane (facing the blood) secretes bicarbonate (HCO3-) in exchange for Cl-. The Cl- moves into the cell against its electrochemical gradient, powered by the downhill movement of HCO3- out of the cell. This HCO3- is produced by the dissociation of carbonic acid (H2CO3), which is formed from CO2 and H2O by the action of the enzyme carbonic anhydrase (abbreviated CA). The Cl- then leaves the apical portion of the membrane by diffusion through a membrane channel. The parietal cells thus secrete HCl into the stomach lumen as they secrete HCO3- into the blood.

Lumen of stomach

Lumen of stomach

■ Figure 18.9 The activation of pepsin. The gastric mucosa secretes the inactive enzyme pepsinogen and hydrochloric acid (HCl). In the presence of HCl, the active enzyme pepsin is produced. Pepsin digests proteins into shorter polypeptides.

The high concentration of HCl from the parietal cells makes gastric juice very acidic, with a pH of less than 2. This strong acidity serves three functions:

1. Ingested proteins are denatured at low pH—that is, their tertiary structure (chapter 2) is altered so that they become more digestible.

2. Under acidic conditions, weak pepsinogen enzymes partially digest each other—this frees the fully active pepsin enzyme as small inhibitory fragments are removed (fig. 18.9).

3. Pepsin is more active under acidic conditions—it has a pH optimum (chapter 4) of about 2.0.

As a result of the activation of pepsin under acidic conditions, the fully active pepsin is able to catalyze the hydrolysis of peptide bonds in the ingested protein. Thus, the cooperative activities of pepsin and HCl permit the partial digestion of food protein in the stomach.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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