Abstract
In mammalian kidneys, NHE3 (luminal type of Na+/H+ exchangers) mediates both net bicarbonate reabsorption at the proximal tubule and H+ excretion for urine acidification at the thick ascending limb. We investigated localization of NHE3 along the nephron and the level of expression in response to acidification. Methods: Expression of NHE1-4 mRNAs was assessed by in situ hybridization through the nephron, such as proximal convoluted tubule (PCT), proximal straight tubule (PST), discending thin limb (DTL), cortical and medullary thick ascending limbs (cTAL and mTAL), distal convoluted tubule (DCT), and collecting ducts (CD). Abundance of NHE3 mRNA was assessed by the same technique under the condition of chronic metabolic acidosis. Results: Blood pH and [HCO3−] were significantly decreased from 7.37 (control, n=5) to 7.17 (acidosis, n=5) and from 23.4 to 12.3 (mmol/L), respectively, on the second day of the experiment, but they returned to a normal level on the 6th day. In control, NHE1 mRNA was ubiquitously present along the nephron. NHE2 mRNA strongly expressed at the TAL and DCT. NHE3 mRNA was present at the PCT, DTL and TAL. NHE4 mRNA was present through the distal part of the nephron. Under chronic (6 d) metabolic acidosis, expression of NHE1, 2, 4 mRNAs were unchanged, but NHE3 mRNA increased dramatically only at mTAL. Conclusion: NHE3 at the mTAL, NOT at the PCT, may play an important role for body pH regulation at least during acidosis. [J Physiol Sci. 2008;58 Suppl:S82]