Editing Α-Ketoglutaric acid (section)

====OXGR1 receptor-dependent bioactions====
OXGR1 (also known as GPR99) is a [[G protein-coupled receptor]], i.e., a [[Receptor (biochemistry)|receptor]] located on the [[Cell membrane|surface membrane of cells]] that binds certain [[Ligand (biochemistry)|ligands]] and is thereby stimulated to activate [[G proteins]] that elicit pre-programmed responses in their parent cells. OXRG1 was identified as a receptor for: '''a)''' α-ketoglutarate in 2004;<ref name="pmid36919698">{{cite journal | vauthors = Zeng YR, Song JB, Wang D, Huang ZX, Zhang C, Sun YP, Shu G, Xiong Y, Guan KL, Ye D, Wang P | title = The immunometabolite itaconate stimulates OXGR1 to promote mucociliary clearance during the pulmonary innate immune response | journal = The Journal of Clinical Investigation | volume = 133 | issue = 6 | pages = | date = March 2023 | pmid = 36919698 | pmc = 10014103 | doi = 10.1172/JCI160463 | url = }}</ref><ref name="pmid38448252">{{cite journal | vauthors = Ye D, Wang P, Chen LL, Guan KL, Xiong Y | title = Itaconate in host inflammation and defense | journal = Trends in Endocrinology and Metabolism | volume = | issue = | pages = | date = March 2024 | pmid = 38448252 | doi = 10.1016/j.tem.2024.02.004 | url = }}</ref> '''b)''' three [[leukotrienes]] viz., [[leukotriene E4|leukotrienes E4]], [[leukotriene C4|C4]], and [[Leukotriene D4|D4]] in 2013.<ref name="pmid23504326">{{cite journal | vauthors = Kanaoka Y, Maekawa A, Austen KF | title = Identification of GPR99 protein as a potential third cysteinyl leukotriene receptor with a preference for leukotriene E4 ligand | journal = The Journal of Biological Chemistry | volume = 288 | issue = 16 | pages = 10967–72 | date = April 2013 | pmid = 23504326 | pmc = 3630866 | doi = 10.1074/jbc.C113.453704 | doi-access = free | url = }}</ref><ref name="pmid31135881">{{cite journal | vauthors = Sasaki F, Yokomizo T | title = The leukotriene receptors as therapeutic targets of inflammatory diseases | journal = International Immunology | volume = 31 | issue = 9 | pages = 607–615 | date = August 2019 | pmid = 31135881 | doi = 10.1093/intimm/dxz044 | url = }}</ref> and '''c)''' [[itaconate]] in 2023.<ref name="pmid36919698"/><ref name="pmid38448252"/> These ligands have the following relative potencies in stimulating responses in OXGR1-bearing cells (Note that LTE4 can stimulate OXGR1 at concentrations far lower than those of the other four ligands):

:::LTE4 >> LTC4 = LTD4 > α-ketoglutarate = itaconate.

It may be difficult to determine if an OXGR1-stimulating agent elicits a functional response by activating OXGR1 as opposed to some other mechanism. To make this distinction, studies have shown that the action of an OXGR1-activating agent on cultured cells, cultured tissues, or animals does not occur or is reduced when these cells, tissues, or animals have been altered so that they do not express or express greatly reduced levels of the OXGR1 protein,<ref name="pmid36919698"/><ref name="pmid38448252"/><ref name="pmid23504326"/><ref name="pmid34179130">{{cite journal | vauthors = Guerrero A, Visniauskas B, Cárdenas P, Figueroa SM, Vivanco J, Salinas-Parra N, Araos P, Nguyen QM, Kassan M, Amador CA, Prieto MC, Gonzalez AA | title = α-Ketoglutarate Upregulates Collecting Duct (Pro)renin Receptor Expression, Tubular Angiotensin II Formation, and Na+ Reabsorption During High Glucose Conditions | journal = Frontiers in Cardiovascular Medicine | volume = 8 | issue = | pages = 644797 | date = 2021 | pmid = 34179130 | pmc = 8220822 | doi = 10.3389/fcvm.2021.644797 | doi-access = free | url = }}</ref> or when their actions are inhibited by an OXGR1 [[receptor antagonist]]s. OXGR1 is inhibited by [[Montelukast]], a well-known inhibitor of the [[cysteinyl leukotriene receptor 1]], i.e., the receptor for LTD4, LTC4, and LTE4. Montelukast also blocks the binding of these leukotrienes to, and thereby inhibits their activation of, OXGR1. One study presented evidence suggesting that α-ketoglutarate binds to OXGR1. It is assumed that Montelukast similarly blocks α-ketoglutarate's binding to,  and thereby inhibits its activation of OXGR1.<ref name="pmid23504326"/><ref name="pmid34179130"/>