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Pendrin mediates both base secretion in response to systemic base load and Cl<jats:sup>\u2212<\/jats:sup> reabsorption in response to systemic volume depletion, manifested as decreased nephron salt and water delivery to the distal nephron. Pendrin\u2010mediated Cl<jats:sup>\u2212<\/jats:sup>\/HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> exchange in the apical membrane is upregulated through stimulation of the \u03b2\u2010IC apical membrane G protein\u2010coupled receptor, 2\u2010oxoglutarate receptor 1 (OXGR1\/GPR99), by its ligand \u03b1\u2010ketoglutarate (\u03b1KG). \u03b1KG is both filtered by the glomerulus and lumenally secreted by proximal tubule apical membrane organic anion transporters (OATs). OXGR1\u2010mediated regulation of Pendrin by \u03b1KG has been documented in transgenic mice and in isolated perfused CCD. However, aspects of the OXGR1 signaling pathway have remained little investigated since its original discovery in lymphocytes. Moreover, no ex vivo cellular system has been reported in which to study the OXGR1 signaling pathway of Type B\u2010IC, a cell type refractory to survival in culture in its differentiated state. As <jats:italic>Xenopus<\/jats:italic> oocytes express robust heterologous Pendrin activity, we investigated OXGR1 regulation of Pendrin in oocytes. Despite functional expression of OXGR1 in oocytes, co\u2010expression of Pendrin and OXGR1 failed to exhibit \u03b1KG\u2010sensitive stimulation of Pendrin\u2010mediated Cl<jats:sup>\u2212<\/jats:sup>\/anion exchange under a wide range of conditions. We conclude that <jats:italic>Xenopus<\/jats:italic> oocytes lack one or more essential molecular components or physical conditions required for OXGR1 to regulate Pendrin activity.<\/jats:p>","DOI":"10.14814\/phy2.15362","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T05:30:04Z","timestamp":1658208604000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Activation of 2\u2010oxoglutarate receptor 1 (<scp>OXGR1<\/scp>) by \u03b1\u2010ketoglutarate (<scp>\u03b1KG<\/scp>) does not detectably stimulate Pendrin\u2010mediated anion exchange in <i>Xenopus<\/i> oocytes"],"prefix":"10.14814","volume":"10","author":[{"given":"John F.","family":"Heneghan","sequence":"first","affiliation":[{"name":"Division of Nephrology Beth Israel Deaconess Medical Center  Boston Massachusetts USA"},{"name":"Department of Medicine Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amar J.","family":"Majmundar","sequence":"additional","affiliation":[{"name":"Division of Nephrology Boston Children's Hospital  Boston Massachusetts USA"},{"name":"Department of Pediatrics Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alicia","family":"Rivera","sequence":"additional","affiliation":[{"name":"Division of Nephrology Beth Israel Deaconess Medical Center  Boston Massachusetts USA"},{"name":"Department of Medicine Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay G.","family":"Wohlgemuth","sequence":"additional","affiliation":[{"name":"Quest Diagnostics  Secaucus New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey S.","family":"Dlott","sequence":"additional","affiliation":[{"name":"Quest Diagnostics  Secaucus New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. 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