Editing Α-Ketoglutaric acid (section)

====Kidney functions====
The [[pendrin]] protein promotes the [[electroneutral exchange]] of tissue [[chloride]] (Cl<sup>−</sup>) for urinary [[bicarbonate]] (HCO<sub>3</sub><sup>−</sup>) in the apical surfaces (i.e., surfaces facing the urine) of the kidney's renal β-intercalated cells (also termed type B intercalated cells) and non-α non-β intercalated cells (also	termed non-A non-B intercalated cells) in the kidney's [[collecting duct system]] (i.e., CDS).<ref name="pmid38110744">{{cite journal | vauthors = Brazier F, Cornière N, Picard N, Chambrey R, Eladari D | title = Pendrin: linking acid base to blood pressure | journal = Pflügers Archiv | volume = 476 | issue = 4 | pages = 533–543 | date = April 2024 | pmid = 38110744 | doi = 10.1007/s00424-023-02897-7 | url = }}</ref> A study in mice found that OXGR1 colocalizes with [[pendrin]] in the [[Collecting duct system#Intercalated cells|β-intercalated cells and non-α non-β intercalated cells]] lining the [[tubules]] of their kidney's CDS. The intercalated cells in the CDS tubules isolated from mice used pendrin in cooperation with the [[electroneutral sodium bicarbonate exchanger 1]] protein to mediate the Cl<sup>−</sup> for HCO<sub>3</sub><sup>−</sup> exchange. α-Ketoglutarate stimulated the rate of this exchange in CDS tubules isolated from control mice (i.e., mice that had the ''Oxgr1'' gene and protein) but not in CDS tubules isolated from ''Oxgr1'' [[gene knockout]] mice (i.e., mice that lacked the ''Oxgr1'' gene and protein). This study also showed that the α-ketoglutarate in the blood of mice filtered through their kidney's [[glomeruli]] into the [[proximal tubules]] and [[loops of Henle]] where it was reabsorbed. Mice drinking water with a [[Basic (chemistry)|basic]] [[pH]] (i.e., >7) due to the addition of [[sodium bicarbonate]] and mice lacking the ''Oxgr1'' gene and protein who drink water without sodium bicarbonate had urines that were more basic (i.e., pH about 7.8) and contained higher levels of urinary α-ketoglutarate than control mice drinking water without this additive. Furthermore, ''Oxgr1'' gene knockout mice drinking sodium bicarbonate-rich water developed [[metabolic alkalosis]] (body tissue pH levels higher than normal) that was associated with blood bicarbonate levels significantly higher and blood chloride levels significantly lower than those in control mice drinking the sodium bicarbonate-rich water.<ref name="pmid23934124"/> Several other studies confirmed these findings and reported that cells in the proximal tubules of mice synthesize α-ketoglutarate and either broke it down thereby reducing its urine levels or secreted it into the tubules' lumens thereby increasing its urine levels.<ref name="pmid28771454">{{cite journal | vauthors = Grimm PR, Welling PA | title = α-Ketoglutarate drives electroneutral NaCl reabsorption in intercalated cells by activating a G-protein coupled receptor, Oxgr1 | journal = Current Opinion in Nephrology and Hypertension | volume = 26 | issue = 5 | pages = 426–433 | date = September 2017 | pmid = 28771454 | doi = 10.1097/MNH.0000000000000353 | url = }}</ref> Another study showed that '''a)''' ''[[In silico]]'' [[computer simulation]]s strongly suggested that α-ketoglutarate bound to mouse OXGPR1; '''b)''' suspensions of canal duct cells isolated from the collecting ducts, loops of Henle, [[Vasa recta (kidney)|vasa recta]], and [[interstitium]] of mouse kidneys raised their cytosolic ionic calcium, i.e., Ca<sup>2+</sup> levels in response to α-ketoglutarate but this response (which is an indicator of cell activation) was blocked by pretreating the cells with Montelukast; and '''c)''' compared to mice not treated with [[streptozotocin]], streptozotocin-induced diabetic mice (an [[animal disease model]] of [[diabetes]]) urinated only a small amount of the ionic sodium ({{chem2|Na+}}) that they drank or received by intravenous injections; Montelukast reversed this defect in the streptozotocin-pretreated mice.<ref name="pmid34179130"/> These results indicate that in mice: '''a)''' α-ketoglutarate stimulates kidney OXGR1 to activate pendrin-mediated reabsorption of sodium and chloride by type B and non-A–non-B intercalated cells; '''b)''' high [[alkaline]] (i.e., sodium bicarbonate) intake produces significant increases in urine pH and α-ketoglutarate levels and impairs secretion of bicarbonate into the CDS tubules' lumens; '''c)''' the [[Acid–base homeostasis|acid–base balance]] (i.e., levels of acids relative to their bases) in the face of high alkali intake depends on the activation of OXGR1 by α-ketoglutarate;<ref name="pmid23934124"/><ref name="pmid28771454"/> '''d)''' alkaline loading directly or indirectly stimulates α-ketoglutarate secretion into the kidney's proximal tubules where further down these tubules it activates OXGR1 and thereby the absorption and secretion of various agents that contribute to restoring a physiologically normal acid-base balance;<ref name="pmid28771454"/> and '''e)''' α-ketoglutarate stimulates OXGR1-bearing CDS cells to raise their levels of cytosolic Ca<sup>2+</sup>) and in diabetic mice (and presumably other conditions involving high levels of blood and/or urine glucose) to increase these cells uptake of {{chem2|Na+}}.<ref name="pmid23934124"/><ref name="pmid34179130"/><ref name="pmid38110744"/><ref name="pmid28771454"/>