What Do Parietal Cells Secrete

Vivo Pathophysiology

The Parietal Cell: Machinery of Acid Secretion

The best-known component of gastric juice is hydrochloric acid, the secretory production of the parietal, or oxyntic cell. It is known that the chapters of the stomach to secrete HCl is almost linearly related to parietal jail cell numbers.

When stimulated, parietal cells secrete HCl at a concentration of roughly 160 mM (equivalent to a pH of 0.8). The acid is secreted into large cannaliculi, deep invaginations of the plasma membrane which are continuous with the lumen of the stomach.

When acid secretion is stimulated at that place is a dramatic change in the morphology of the membranes of the parietal cell. Cytoplasmic tubulovesicular membranes which are arable in the resting cell virtually disappear in concert with a large increase in the cannalicular membrane. It appears that the proton pump besides as potassium and chloride conductance channels initially reside on intracellular membranes and are transported to and fused into the cannalicular membrane but prior to acid secretion.

The epithelium of the stomach is intrinsically resistant to the damaging effects of gastric acrid and other insults. Nonetheless, excessive secretion of gastric acrid is a major problem in human and, to a lesser extent, animal populations, leading to gastritis, gastric ulcers and peptic acrid affliction. Every bit a consequence, the parietal cell and the mechanisms it uses to secrete acid have been studied extensively, leading to evolution of several drugs useful for suppressing acid secretion.

Mechanism of Acid Secretion

The hydrogen ion concentration in parietal cell secretions is roughly 3 million fold college than in blood, and chloride is secreted against both a concentration and electric gradient. Thus, the power of the partietal cell to secrete acid is dependent on agile transport.

The key player in acid secretion is a H+/Grand+ ATPase or "proton pump" located in the cannalicular membrane. This ATPase is magnesium-dependent, and not inhibitable past ouabain. The current model for explaining acid secretion is as follows:

Hydrogen ions are generated inside the parietal cell from dissociation of water. The hydroxyl ions formed in this process apace combine with carbon dioxide to form bicarbonate ion, a reaction cataylzed by carbonic anhydrase.
Bicarbonate is transported out of the basolateral membrane in commutation for chloride. The outflow of bicarbonate into claret results in a slight elevation of blood pH known equally the "alkaline metal tide". This process serves to maintain intracellular pH in the parietal cell.
Chloride and potassium ions are transported into the lumen of the cannaliculus by conductance channels, and such is necessary for secretion of acrid.
Hydrogen ion is pumped out of the jail cell, into the lumen, in exchange for potassium through the activity of the proton pump; potassium is thus effectively recycled.
Aggregating of osmotically-active hydrogen ion in the cannaliculus generates an osmotic gradient beyond the membrane that results in outward diffusion of h2o - the resulting gastric juice is 155 mM HCl and fifteen mM KCl with a small amount of NaCl.

A primal substrate in the production of gastric acid is CO₂, and diffusion of CO₂ through the basal surface of the parietal appears to be the rate limiting pace in acid synthesis. Interestingly, this biochemical principle has been validated past studying gastric function in alligators. These reptiles produce huge amounts of gastric acid later on ingestion of a large carcass, and abundant acid seems to be important in speeding digestion of bone. Alligators have a vascular shunt that diverts CO₂-rich venous claret to the stomach rather than straight back to the lungs, increasing the amount of CO₂ that diffuses into parietal cells and thereby enhancing synthesis of acrid.

Control of Acrid Secretion

Parietal cells bear receptors for three stimulators of acid secretion, reflecting a triumverate of neural, paracrine and endocrine control:

Acetylcholine (muscarinic type receptor)
Gastrin
Histamine (H2 type receptor)

Histamine from enterochromaffin-similar cells may well be the primary modulator, but the magnitude of the stimulus appears to outcome from a complex additive or multiplicative interaction of signals of each type. For example, the depression amounts of histamine released constantly 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, acrid secretion is strongly forced. Additionally, pharmacologic antagonists of each of these molecules tin can cake acid secretion.

Histamine's upshot on the parietal jail cell is to activate adenylate cyclase, leading to peak of intracellular cyclic AMP concentrations and activation of protein kinase A (PKA). 1 result of PKA activation is phosphorylation of cytoskeletal proteins involved in transport of the H+/K+ ATPase from cytoplasm to plasma membrane. Binding of acetylcholine and gastrin both issue in meridian of intracellular calcium concentrations.

Several additional mediators have been shown to issue in gastric acid secretion when infused into animals and people, including calcium, enkephalin and bombesin. Calcium and bombesin both simulate gastrin release, while opiate receptors have been identified on parietal cells. Information technology is unclear whether these molecules have a significant physiologic function in parietal jail cell function.

A variety of substances are capable of reducing gastric acid secretion when infused intravenously, including prostaglandin Eastward_ii and several peptides hormones, including secretin, gastric inhibitory peptide, glucagon and somatostatin. PGE_two, secretin and somatostatin may be physiologic regulators. Somatostatin inhibits secretion of gastrin and histamine, and appears to have a directly inhibitory effect on the parietal cell.

References and Reviews

Farmer CG, Uriona TJ, Olsen DB, Steenblik M, Sanders Thou. The right-to-left shunt of crocodilians serves digestion. Physiol Biochem Zool 2008; 81:125-137.
Forte JG, Zhu L. Apical Recycling of the Gastric Parietal Prison cell H,K-ATPase. Annu Rev Physiol 72:273–96, 2010
Kidder GW, Montgomery CW. CO2 improvidence into frog gastric mucosa as charge per unit-limiting gene in acid secretion. Am J Physiol 1974; 227:300–304.
Samuelson LC, Hinkle KL: Insights into the regulation of gastric acid secretion through analysis of genetically engineered mice. Annu Rev Physiol 65:383-400, 2003.
Yao 10, Forte JG: Prison cell biology of acid secretion by the parietal prison cell. Annu Rev Physiol 65:103-131, 2003.

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