Editing Parietal cell (section)

===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>