Oxyntic cell

Figure 18-17 Schematic diagram of an acid-producing oxyntic gland of the stomach. The normal human stomach contains about 109 parietal (oxyntic) cells located in the walls of these glands. From Wolfe and Soil.279 Modified from Ito. These glands also produce mucus, whose role in protecting the stomach lining from the high acidity is uncertain.280...

Parietal (oxyntic) cells located predominantly in the body and fundus of the stomach secrete hydrochloric acid. The gastric pH is not constant owing to variation in acid secretion and gastric content. The pH in the stomach at different states of feeding and various parts of the small intestine is shown in Table 2.1. The mucus layer restricts the diffusion of hydrogen ions secreted by the intestinal epithelial cells. As a result, the pH of this 700- m-thick microclimate region is on the order 5.8 to... 

The involvement of the proton pump (H+, K+-ATPase) in the regulation of gastric acid secretion by the parietal (oxyntic) cell is well established. 

Proton pump inhibitors inhibit the H/K-ATPase (proton pump) in oxyntic cells of the stomach, the final common pathway in the secretion of gastric acid in response to a variety of stimuli, such as gastrin and histamine. Their use in acid-related disorders has been extensively reviewed (1-3). 

The acid. secretory unit of the gastric mucosa is the parietal (oxyntic) cell. Parietal cells contain a hydrogen ion pump, a unique -ATPase system that secretes HjO in... 

A Ganser, J. F orte (110) Discovery of H /K -ATPase in oxyntic cells of the bullfrog... 

In 1882 Phillip Stohr of Wurzburg described vacuoles in oxyntic cells, but in 1898 Erik Muller of the Karolinska Institute in Stockholm demonstrated that the vacuoles are really parts of a canalicular system within the cells that communicates directly with the lumen of the gland s tubule or indirectly by means of a secretory capillary lying between chief cells. In Muller s Figure 6, the intracellular canaliculi of a rabbit s parietal cell are particularly well demonstrated by a Golgi stain."... 

Not everyone agreed on how the oxyntic cells discharge their responsibility of secreting acid. Some thought the cells directly secrete the acid that appears on the surface of the mucosa others thought the cells secrete a precursor that yields acid only in the tubules or on the surface of the mucosa. 

The third requirement is the demonstration of a complete biochemical and biophysical machinery to accomplish secretion of acid in one direction and an equivalent amount of base in the other. Albert Mathews of the University of Cincinnati proposed that oxyntic cells secrete ammonium chloride, and that as a solution of ammonium chloride passes up the gastric tubules, ammonium ions are absorbed and replaced by hydrogen ions. He did not show that oxyntic cells produce ammonium chloride or that the tubule cells consume ammonium. 

I wanted carbonic anhydrase to be found only in the oxyntic cells, but no matter how I reexamined my data, I found an excess of the enzyme that could only be accounted for by its presence in epithelial cells (Fig. 1-17). 

Figure 1-16. Ordinates, carbonic anhydrase concentration in arbitrary units in slices of oxyntic mucosa of the cat. Abscissae, 1,000 oxyntic cells in adjacent slices of the oxyntic mucosa of the cat. (From Davenport H W. Gastric carbonic anhydrase. I Physiol Lond 97 32-43, 1939.)... 

Figure 1-18. Left, abscissae, concentration of thiocyanate in mM ordinates, ratio of inactive to active carbonic anhydfase in the solution. Center abscissae, concentration of active carbonic anhydrase in arbitrary units in the presence of 1.78 mM thiocyanate ordinates, concentration of inactive carbonic anhydrase in the solution in the same arbitrary units. Right abscissae, concentration of thiocyanate in the oxyntic cells calculated as described in the text ordinates, hydrogen ion concentration in gastric juice as a percentage of uninhibited concentration under maximal histamine stimulation. The dotted line is the regression line calculated from the data. The solid line is the theoretical line derived from the assumptions described in the text. (From Davenport HW. The inhibition of carbonic anhydrase and of gastric acid secretion by thiocyanate. Am / Physiol 129 505-514, 1940.)...

When Roughton himself was working at the Harvard Fatigue Laboratory during the war, he and his collaborators found that only when human blood concentration of sulfanilamide is 3 to 4 mg% is there some evidence that during extreme exercise the limit of carbonic anhydrase s ability to catalyze dehydration of plasma bicarbonate has been approached. Later I found that more than 99.5% of the carbonic anhydrase of erythrocytes must be inhibited before there is 50% inhibition of the catalyzed uptake of carbon dioxide."" There is 1,000 times more enzyme in the erythrocytes than is required, and the same is true of oxyntic cells (Fig. 1-20). 

Conway, like everyone else who constructed a theory of the mechanism of acid secretion, believed that the crucial reaction separating hydrogen ions from the interior of the yeast or oxyntic cell occurs in an outer region of the cell. Until about 1970, that outer region of the yeast cell or the canalicular membrane in which separation occurs was nothing more than a single or double line on a piece of paper. The properties attributed to it were entirely hypothetical. 

Conway adduced no experimental evidence of his own to support his theory of the behavior of oxyntic cells, and his evidence for a redox reaction in the yeast cell that exchanges hydrogen for potassium ions was, in contrast to the elaborate nature of his argument, extremely sketchy. Oxygen is required, and so is an oxidizable substrate secretion is inhibited by azide, monoiodoacetate, and 2,4-dinitrophenol and that is all. 

Davies s first paper, published in 1948, began with an elaborate demonstration of what no one seriously doubted that for every hydrogen ion the mucosa secretes, it takes up one molecule of carbon dioxide provided either by its own metabolism or by ambient carbon dioxide. After it is hydrated and the resultant carbonic acid ionized, the oxyntic cell then has a hydrogen ion to maintain intracellular neutrality and a bicarbonate ion to exchange for chloride.Davies and F. J. W. Roughton... 

Davies stressed the importance of an adequate supply of carbon dioxide for optimal secretion for the reason that some investigators, notably myself, performed similar experiments in which tied sacs of mucosa were incubated in phosphate-buffered salt solution with no carbon dioxide in the gas phase. Davies allowed that in such an experimental situation, carbon dioxide produced by the tissue s metabolism could be recycled so that phosphate could become the ultimate determinant of the oxyntic cells internal neutrality, but he repeatedly asserted that the gastric mucosa does not secrete acid at its maximal rate in the absence of exogenous carbon dioxide. 

Everyone who studied the mechanism of acid secretion after 1941 attempted to identify the means by which thiocyanate inhibits acid secretion. At one time Davies thought SCN might plug the pores through which Cr passes into oxyntic cells. 

It is difficult to partition electrolytes between intracellular and extracellular spaces, because the calculated volume of extracellular space depends upon the marker used for its estimation. The volume of distribution of "C-inulin (MW about 5,000) in the mucosa is greater than that of radioiodinated serum albumin (RISA, MW 68,000), and the distribution of both is smaller than that of nonme-tabolized "C-arabinose (Fig. 1-29). The volumes of distribution of "C-mannitol and "C-sucrose are the same as those of arabinose. It is likely that the volume of distribution of inulin or RISA is close to the true volume of extracellular space, although it is possible that RISA is excluded from some extracellular water containing collagenous tissue. Calculations based on the conventional assumption that all sodium is extracellular and that RISA space is the true extracellular space are given in Table 1-7.1 concluded that oxyntic cells contain some sodium. 

In the next 5 years, David Click in Milwaukee and Susumu Ito s students at Harvard refined the procedure of layering oxyntic cells. Click demonstrated that his oriented layer was stimulated to transport chloride by histamine and carbachol and was inhibited by prostaglandin Ito s students obtained a monolayer of mouse oxyntic cells on a Millipore membrane, and they demonstrated by electron microscopy that the cells were oriented with their canaliculi continuous with the fluid on one side of the membrane. The cells transferred chloride against an electrical gradient. 

Andrew Soil s brilliant work, demonstrating acid secretion by dog isolated oxyntic cells, was just beginning in 1975. It will not be described here. ... 

---