Editing Parietal cell (section)

==Function==
===Hydrochloric acid secretion===
Hydrochloric acid is formed in the following manner:
* Hydrogen ions are formed from the dissociation of carbonic acid. Water is a very minor source of hydrogen ions in comparison to carbonic acid. Carbonic acid is formed from [[carbon dioxide]] and water by [[carbonic anhydrase]].
* The bicarbonate ion (HCO<sub>3</sub><sup>−</sup>) is exchanged for a chloride ion (Cl<sup>−</sup>) on the basal side of the cell and the bicarbonate diffuses into the venous blood, leading to an [[alkaline tide]] phenomenon.
* [[Potassium]] (K<sup>+</sup>) and chloride (Cl<sup>−</sup>) ions diffuse into the [[Parietal cell#Canaliculus|canaliculi]].
* Hydrogen ions are pumped out of the cell into the canaliculi in exchange for potassium ions, via the [[hydrogen potassium ATPase|H<sup>+</sup>/K<sup>+</sup>-ATPase]]. These pumps are increased in number on luminal side by fusion of tubulovesicles during activation of parietal cells and removed during deactivation. This pump maintains a million-fold difference in proton concentration.<ref>{{cite journal |last1=Abe |first1=Kazuhiro |last2=Irie |first2=Katsumasa |last3=Nakanishi |first3=Hanayo |last4=Suzuki |first4=Hiroshi |last5=Fujiyoshi |first5=Yoshinori |title=Crystal structures of the gastric proton pump |journal=Nature |date=April 2018 |volume=556 |issue=7700 |pages=214–218 |doi=10.1038/s41586-018-0003-8}}</ref> ATP is provided by the numerous mitochondria.

[[File:Parietal cells.jpg|thumb|Human parietal cells (pink staining) – stomach.]]
As a result of the cellular export of hydrogen ions, the gastric lumen is maintained as a highly acidic environment. The acidity aids in digestion of food by promoting the unfolding (or [[Denaturation (biochemistry)|denaturing]]) of ingested [[protein]]s.  As proteins unfold, the [[peptide bonds]] linking component [[amino acids]] are exposed.  Gastric HCl simultaneously cleaves [[pepsinogen]], a [[zymogen]], into active [[pepsin]], an endopeptidase that advances the digestive process by breaking the now-exposed peptide bonds, a process known as [[proteolysis]].

===Regulation===

Parietal cells [[secretion|secrete]] acid in response to three types of [[stimulus (physiology)|stimuli]]:<ref>{{cite book|last=Boulpaep|first=Walter|title=Medical Physiology|year=2009|publisher=Saunders|location=Philadelphia|isbn=978-1-4160-3115-4|pages=898–899}}</ref>
* [[Histamine]], stimulating [[Histamine H2 receptor|H<sub>2</sub> histamine receptors]] (most significant contribution).
* [[Acetylcholine]] (ACh), from [[parasympathetic]] activity via the [[vagus nerve]] and enteric nervous system, stimulating [[Muscarinic acetylcholine receptor M3|M<sub>3</sub> receptors]].<ref name="M3 receptor">{{cite web|title=Gastric acid secretion - Homo sapiens|url=http://www.genome.jp/dbget-bin/show_pathway?hsa04971+1131|publisher=KEGG|access-date=June 1, 2011}}</ref>
* [[Gastrin]], stimulating [[Cholecystokinin B receptor|CCK2 receptors]] (least significant contribution, but also causes histamine secretion by local [[Enterochromaffin-like cell|ECL cells]]).
Activation of histamine through H<sub>2</sub> receptor causes increases in the intracellular [[Cyclic adenosine monophosphate|cAMP]] level, while ACh through M<sub>3</sub> receptor and gastrin through CCK2 receptor increases intracellular calcium level. These receptors are present on basolateral side of membrane.

Increased cAMP level results in increased protein kinase A. Protein kinase A phosphorylates proteins involved in the transport of [[Hydrogen potassium ATPase|H<sup>+</sup>/K<sup>+</sup>-ATPase]] from the cytoplasm to the [[cell membrane]].  This causes resorption of K<sup>+</sup> ions and secretion of H<sup>+</sup> ions. The [[pH]] of the secreted fluid can fall by 0.8.

Gastrin primarily induces acid-secretion indirectly, increasing histamine synthesis in [[Enterochromaffin-like cell|ECL cells]], which in turn signal parietal cells via histamine release and H<sub>2</sub> stimulation.<ref>Waldum, Helge L., Kleveland, Per M., et al. (2009)'Interactions between gastric acid secretagogues and the localization of the gastrin receptor', Scandinavian Journal of Gastroenterology, 44:4,390—393.</ref> Gastrin itself has no effect on the maximum histamine-stimulated gastric acid secretion.<ref>Kleveland PM, Waldum HL, Larsson M. Gastric acid secretion in the totally isolated, vascularly perfused rat stomach. A selective muscarinic-1 agent does, whereas gastrin does not, augment maximal histamine-stimulated acid secretion. Scandinavian Journal of Gastroenterology, 1987;22:705–713.</ref>

The effect of histamine, acetylcholine and gastrin is synergistic, that is, effect of two simultaneously is more than additive of effect of the two individually. It helps in non-linear increase of secretion with stimuli physiologically.<ref>{{Cite book|title = Ganong's Review of Medical Physiology 24th edition|publisher = Lange}}</ref>

===Intrinsic factor secretion===
Parietal cells also produce a [[glycoprotein]] known as [[intrinsic factor]]. Intrinsic factor is required for the absorption of [[Vitamin B12|vitamin B{{sub|12}}]] in the diet.  A long-term [[Vitamin B12 deficiency|deficiency in vitamin B<sub>12</sub>]] can lead to [[megaloblastic anemia]], characterized by large fragile [[red blood cells]]. [[Pernicious anaemia]] results from autoimmune destruction of gastric parietal cells, precluding the synthesis of intrinsic factor and, by extension, absorption of vitamin B<sub>12</sub>. Pernicious anemia also leads to megaloblastic anemia. [[Atrophic gastritis]], particularly in the elderly, will cause an inability to absorb B<sub>12</sub> and can lead to deficiencies such as decreased DNA synthesis and [[nucleotide]] metabolism in the bone marrow.