We are talking about the cells found in the gastric mucosa.
Oxyntic cells, or parietal cells, are the cells of the stomach epithelium that secrete gastric acid and intrinsic factor acetylcholine (M3 receptors) and gastrin (CCK2 receptors).
Histamine receptors act by increasing intracellular cAMP, while muscarinic and gastrin receptors increase intracellular Ca2 + levels.
Both cAMP and Ca2 + act through protein kinases to increase acid transport to the stomach.
Gastrin is more important indirectly by increasing histamine synthesis in ECL cells, since gastrin has no effect on maximal histamine-stimulated gastric acid secretion.
Parietal cells contain an extensive secretory network (called canaliculi) from which HCl is secreted by active transport in the stomach.
The enzyme hydrogen potassium ATPase (H + / K + ATPase) is unique to parietal cells and transports H + against a concentration gradient of approximately 3 million to 1, which is the steepest ion gradient formed in the human body.
Parietal cells also produce intrinsic factor. Intrinsic factor is necessary for the absorption of vitamin B12 in the diet.
A long-term deficiency of vitamin B12 can lead to megaloblastic anemia, characterized by large fragile red blood cells.
Pernicious anemia is a condition in which intrinsic factor is not produced and leads to the same type of anemia.
Atrophic gastritis, particularly in the elderly, will cause an inability to absorb B12 and can lead to deficiencies such as decreased DNA synthesis and nucleotide metabolism in the bone marrow.
Physiology of Oxyntic Cells
Oxyntic cells parietal cells secrete acid and intrinsic factor, a glycoprotein that is required for the absorption of cobalamin (vitamin B 12) in the ileum.
Oxyntic cells have a very distinctive morphology. These are large, triangular cells with a central nucleus, a large number of mitochondria, intracellular tubulovesicular membranes, and canalicular structures.
Oxyntic cells have two characteristic membrane systems. Mammalian intracellular canaliculi are specialized networks of narrow channels lined with numerous microvilli. The other common to all oxyntic cells are the tubulovesicles, a system of tubules and vesicles.
The tubulovesicular compartment is drastically depleted during peak gastric acid secretion and this coincides with an increase in cell surface membrane area.
A plausible explanation for this process is the fusion and transfer of the tubulovesicular membranes to the plasma membrane.
However, for many years there was no convincing evidence of connections between these two membrane systems.
How tubulovesicular membranes transform into plasma membranes without demonstrable connections has been an enigma for electron microscopists.
A canaliculus is an adaptation found in gastric oxyntic cells.
It is a small channel, which serves to increase the surface area, for example, for secretion.
The oxyntic cell membrane is dynamic; The numbers of canaliculi increase and decrease according to the secretory need.
This is accomplished by fusing the canalicular precursors, or “tubulovesicles,” with the membrane to increase surface area, and reciprocal endocytosis of the canaliculi (reforming the tubulovesicles) to decrease it.
- Oxyntic cell hyperplasia.
- Peptic ulcers.
- Pernicious anemia.
Acid secretion mechanism
The best known component of gastric juice is hydrochloric acid, the secretory product of oxyntic or parietal cells. The stomach’s ability to secrete HCl is known to be almost linearly related to oxyntic cell numbers.
When stimulated, parietal cells secrete HCl at a concentration of approximately 160 mM (equivalent to a pH of 0.8). Acid is secreted in large cannallicles, deep invaginations of the plasma membrane that are continuous with the lumen of the stomach.
When acid secretion is stimulated, there is a dramatic change in the morphology of the oxyntic cell membranes.
The cytoplasmic tubulovesicular membranes that are abundant in the resting cell virtually disappear in concert with a large enlargement of the cannalicular membrane.
It appears that the proton pump as well as the potassium and chloride conductance channels initially reside in the intracellular membranes and are transported and fused in the cannalicular membrane just prior to acid secretion.
The stomach lining is inherently resistant to the damaging effects of gastric acid and other insults. However, excessive gastric acid secretion is a major problem in human populations and, to a lesser extent, in animals, leading to gastritis, gastric ulcers, and peptic acid disease.
As a consequence, the parietal cell and the mechanisms it uses to secrete acid have been extensively studied, leading to the development of several drugs useful for suppressing acid secretion.
Acid secretion mechanism
The concentration of hydrogen ions in parietal cell secretions is approximately 3 million higher than in blood, and chloride is secreted against both the concentration and the electrical gradient. Therefore, the ability of the partial cell to secrete acid is dependent on active transport.
The key player in acid secretion is an H + / K + ATPase or “proton pump” located in the cannalicular membrane. This ATPase is magnesium dependent, and it is not inhibited by ouabain. The current model to explain acid secretion is as follows:
Hydrogen ions are generated within the parietal cell from the dissociation of water. The hydroxyl ions formed in this process quickly combine with carbon dioxide to form a bicarbonate ion, a reaction cataylized by carbonic anhydrase.
Bicarbonate is transported outside the basolateral membrane in exchange for chloride. The release of bicarbonate into the blood results in a slight rise in the pH of the blood, known as the “alkaline tide.” This process serves to maintain intracellular pH in the parietal cell.
Chloride and potassium ions are transported to the channel lumen by conductance channels, and this is necessary for acid secretion.
The hydrogen ion is pumped out of the cell, into the lumen, in exchange for potassium through the action of the proton pump; Potassium is thus effectively recycled.
The accumulation of osmotically active hydrogen ions in the cannaliculus generates an osmotic gradient across the membrane that produces an external diffusion of the water; the resulting gastric juice is 155 mM HCl and 15 mM KCl with a small amount of NaCl.
A key substrate in gastric acid production is CO 2, and diffusion of CO 2 across the basal parietal surface appears to be the rate-limiting step in acid synthesis. Interestingly, this biochemical principle has been validated by studying gastric function in alligators.
These reptiles produce enormous amounts of gastric acid after ingestion of a large carcass, and the abundant acid appears to be important in speeding up bone digestion.
Alligators have a vascular bypass that diverts CO 2-rich venous blood to the stomach rather than directly back to the lungs, increasing the amount of CO 2 diffused into the parietal cells and thus increasing synthesis acid.
Control of acid secretion
Parietal cells have receptors for three stimulators of acid secretion, reflecting a triumphalate of neural, paracrine, and endocrine control:
- Acetylcholine (muscarinic-like receptor).
- Histamine (H2 receptor).
The histamine of enterochromaffin-like cells may be the primary modulator, but the magnitude of the stimulus appears to be the result of an additive complex or multiplicative interaction of signals of each type.
For example, the low amounts of histamine that are constantly released from mast cells in the gastric mucosa only weakly stimulate acid secretion, and similarly for low levels of gastrin or acetylcholine.
However, when low levels of each are present, acid secretion is strongly forced. Furthermore, pharmacological antagonists of each of these molecules can block acid secretion.
The effect of histamine on the parietal cell is to activate adenylate cyclase, leading to elevated intracellular cyclic AMP concentrations and activation of protein kinase A (PKA).
One effect of PKA activation is the phosphorylation of cytoskeletal proteins involved in the transport of ATPase H + / K + from the cytoplasm to the plasma membrane. The binding of acetylcholine and gastrin results in an elevation of intracellular calcium concentrations.
Several additional mediators have been shown to produce gastric acid secretion when injected into animals and people, including calcium, enkephalin, and bombesin.
Calcium and bombesin simulate gastrin release, while opiate receptors have been identified in parietal cells. It is not clear whether these molecules have a significant physiological role in parietal cell function.
A variety of substances are capable of reducing gastric acid secretion when administered intravenously, including prostaglandin E 2 and various peptide hormones, including secretin, gastric inhibitory peptide, glucagon, and somatostatin.
PGE 2, secretin, and somatostatin can be physiological regulators. Somatostatin inhibits gastrin and histamine secretion, and appears to have a direct inhibitory effect on the parietal cell.