Activation of 2-oxoglutarate receptor 1 (OXGR1) by α-ketoglutarate (αKG) does not detectably stimulate Pendrin-mediated anion exchange in Xenopus oocytes
© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society..
SLC26A4/Pendrin is the major electroneutral Cl- /HCO3- exchanger of the apical membrane of the Type B intercalated cell (IC) of the connecting segment (CNT) and cortical collecting duct (CCD). Pendrin mediates both base secretion in response to systemic base load and Cl- reabsorption in response to systemic volume depletion, manifested as decreased nephron salt and water delivery to the distal nephron. Pendrin-mediated Cl- /HCO3- exchange in the apical membrane is upregulated through stimulation of the β-IC apical membrane G protein-coupled receptor, 2-oxoglutarate receptor 1 (OXGR1/GPR99), by its ligand α-ketoglutarate (αKG). αKG is both filtered by the glomerulus and lumenally secreted by proximal tubule apical membrane organic anion transporters (OATs). OXGR1-mediated regulation of Pendrin by αKG 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-IC, a cell type refractory to survival in culture in its differentiated state. As Xenopus oocytes express robust heterologous Pendrin activity, we investigated OXGR1 regulation of Pendrin in oocytes. Despite functional expression of OXGR1 in oocytes, co-expression of Pendrin and OXGR1 failed to exhibit αKG-sensitive stimulation of Pendrin-mediated Cl- /anion exchange under a wide range of conditions. We conclude that Xenopus oocytes lack one or more essential molecular components or physical conditions required for OXGR1 to regulate Pendrin activity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Physiological reports - 10(2022), 14 vom: 30. Juli, Seite e15362 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Heneghan, John F [VerfasserIn] |
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| Links: |
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| Themen: |
Anions |
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| Anmerkungen: |
Date Completed 21.07.2022 Date Revised 11.12.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.14814/phy2.15362 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Heneghan, John F |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Activation of 2-oxoglutarate receptor 1 (OXGR1) by α-ketoglutarate (αKG) does not detectably stimulate Pendrin-mediated anion exchange in Xenopus oocytes |
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| 520 | |a © 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society. | ||
| 520 | |a SLC26A4/Pendrin is the major electroneutral Cl- /HCO3- exchanger of the apical membrane of the Type B intercalated cell (IC) of the connecting segment (CNT) and cortical collecting duct (CCD). Pendrin mediates both base secretion in response to systemic base load and Cl- reabsorption in response to systemic volume depletion, manifested as decreased nephron salt and water delivery to the distal nephron. Pendrin-mediated Cl- /HCO3- exchange in the apical membrane is upregulated through stimulation of the β-IC apical membrane G protein-coupled receptor, 2-oxoglutarate receptor 1 (OXGR1/GPR99), by its ligand α-ketoglutarate (αKG). αKG is both filtered by the glomerulus and lumenally secreted by proximal tubule apical membrane organic anion transporters (OATs). OXGR1-mediated regulation of Pendrin by αKG 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-IC, a cell type refractory to survival in culture in its differentiated state. As Xenopus oocytes express robust heterologous Pendrin activity, we investigated OXGR1 regulation of Pendrin in oocytes. Despite functional expression of OXGR1 in oocytes, co-expression of Pendrin and OXGR1 failed to exhibit αKG-sensitive stimulation of Pendrin-mediated Cl- /anion exchange under a wide range of conditions. We conclude that Xenopus oocytes lack one or more essential molecular components or physical conditions required for OXGR1 to regulate Pendrin activity | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Majmundar, Amar J |e verfasserin |4 aut | |
| 700 | 1 | |a Rivera, Alicia |e verfasserin |4 aut | |
| 700 | 1 | |a Wohlgemuth, Jay G |e verfasserin |4 aut | |
| 700 | 1 | |a Dlott, Jeffrey S |e verfasserin |4 aut | |
| 700 | 1 | |a Snyder, L Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Hildebrandt, Friedhelm |e verfasserin |4 aut | |
| 700 | 1 | |a Alper, Seth L |e verfasserin |4 aut | |
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