Figure 4.

Role of α-ketoglutarate and its receptor, OXGR1, in the regulation of renal Na⁺ transport. α-ketoglutarate (αKG) is freely filtered by the glomerulus. During alkalosis, Na⁺ reabsorption in the proximal segment is reduced and the reabsorption of αKG is blunted, increasing its concentration in the lumen. This high level of αKG delivered to the distal tubule may activate its receptor in the B-intercalated cells. The signalling pathway triggered by this activation is still unknown but activates the Pds/NDBCE system, leading to an increased Na⁺ reabsorption. In case of acidosis, the filtered pool of αKG is reabsorbed by the proximal tubule, decreasing its luminal concentration and blunting the activation of OXGR1 in the CD. In this case, the reabsorption of Na⁺ in the distal nephron is not stimulated. CD: Collecting duct; NDBCE: Na⁺-driven bicarbonate/Cl^- exchanger; OXGR1: 2-oxoglutarate receptor 1; αKG: α-ketoglutarate.