Fcp

Parietal cell

Substituted Benzimidazole (e.g., Omeprazole)

FIGURE 8-13 Model of agonist stimulation of a parietal cell leading to the secretion of acid. The parietal cell (outer cell membrane) has receptors for gastrin (G), acetylcholine (AC), and histamine (H), as well as for prostaglandins (PGE). The main stimulants of HC1 acid secretion are G, AC, and H; collectively they are believed to activate, via a G protein, adenylate cyclase, which eventually leads to an increase in intracellular [Ca2+], and protein kinases, which initiate by as yet unknown mechanisms the secretion of acid (see Figure 8-14). The secretion of HC1 can be blocked by PGE, proglumide, which blocks the gastrin receptor, atropine, which blocks the AC receptor, and certain drugs such as omeprazole which interacts with the H+,K+ ATPase. [This figure was adapted from Wolfe, M. M., and Soil, A. H. (1988). The physiology of gastric acid secretion, New Engl. ]. Med. 319, 1707-1715.]

priate cholinergic or peptidergic nerves leading to the pancreas can stimulate exocrine pancreatic secretions (see Figure 8-15).

Pancreatic secretions of electrolytes and H20 from the ductular and centroacinar cells are primarily under the influence of secretin. Secretin is known to stimulate intracellular cAMP in these cells, which activates unknown factors necessary to alter the secretory cell membrane permeability to sodium and hydrogen ions. Thus, there is an increased exchange of external Na+ ions for internal H+ ions. The increased concentration of extracellular H+ lowers the local pH, which then increases the production of C02 from circulating bicarbonate. This C02 then diffuses into the cells, where it combines with water to form carbonic acid (mediated by carbonic anhydrase) and results in the production of HC03", which can be utilized for secretion.

The pancreatic secretion of digestive enzymes occurs in the acinar cells of the exocrine pancreas under the influence of CCK. In the pancreatic acinar cells, CCK interacts with a receptor present on the outer cell membrane. This activates a G protein-coupled signal transduction pathway (see Figure 8-15) to ultimately stimulate the secretion of amylase, trypsinogen, and chymotrypsinogen stored in secretory granules.

2. Biliary Secretion

Hormonal regulation of bile secretion, primarily by CCK and secretin, occurs by action on the ductules and ducts of the gallbladder. Table 8-11 presents the

FIGURE 8-14 Schematic model describing the production of hydrochloric acid by the parietal cell. The H+ ions that are secreted are generated inside the parietal cell by the action of carbonic anhydrase-mediated conversion of COz + H20 into H2C03 —> H" + HCO, . The resulting bicarbonate is exported into the plasma compartment in a 1:1 exchange for CI . The H+ and Cr are then secreted into the lumen of the cell via the integrated actions of a Na+,H+ ATPase and a symport-combined transfer of K+CL to the lumen. Thus, for every H+Cr secreted, a K+ ion makes a round trip from the parietal cell —> lumen —> parietal cell. [Modified with permission from Rang, H. P., Dale, M. M., Ritter, J. M., and Gardener, P. (1995). "Pharmacology," pp. 386. Churchill-Livingstone, New York.]

FIGURE 8-14 Schematic model describing the production of hydrochloric acid by the parietal cell. The H+ ions that are secreted are generated inside the parietal cell by the action of carbonic anhydrase-mediated conversion of COz + H20 into H2C03 —> H" + HCO, . The resulting bicarbonate is exported into the plasma compartment in a 1:1 exchange for CI . The H+ and Cr are then secreted into the lumen of the cell via the integrated actions of a Na+,H+ ATPase and a symport-combined transfer of K+CL to the lumen. Thus, for every H+Cr secreted, a K+ ion makes a round trip from the parietal cell —> lumen —> parietal cell. [Modified with permission from Rang, H. P., Dale, M. M., Ritter, J. M., and Gardener, P. (1995). "Pharmacology," pp. 386. Churchill-Livingstone, New York.]

major components of human bile. These constituents are secreted into the intestinal lumen in response to dietary fat and they act as detergents to disrupt and

TABLE 8-10 Composition of Human Pancreatic Juice"

Components

TABLE 8-10 Composition of Human Pancreatic Juice"

Components

Cations

Na+, K+,

Ca2+, Mg2+, pH «8.0

Anions

hco3-

, CI", SO42-, HP042"

Digestive enzymes

Activator

Substrate

Trypsinogen

Enteropeptides Proteins, polypeptides

Chymotrypsinogen

Trypsin

Proteins, polypeptides

Prolactases

Trypsin

Elastin, other proteins

Procarboxypeptidase A

Trypsin

Proteins, polypeptides

Procarboxypeptidase B

Trypsin

Proteins, polypeptides

Prolipase

Trypsin

Fat droplets

Pancreatic lipase

Trypsin

Triglycerides

Cholesterol ester

Trypsin

Cholesterol esters

hydrolase

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