Stimulation of renal sulfate secretion by metabolic acidosis requires Na+/H+ exchange induction and carbonic anhydrase.
The acute effect of metabolic acidosis on SO(4)(2-) secretion by the marine teleost renal proximal tubule was examined. Metabolic acidosis was mimicked in primary cultures of winter flounder renal proximal tubule epithelium (fPTCs) mounted in Ussing chambers by reducing interstitial pH to 7.1 (normally 7.7). fPTCs with metabolic acidosis secreted SO(4)(2-) at a net rate that was 40% higher than in paired isohydric controls (pH 7.7 on interstitium). The stimulation was completely blocked by the carbonic anhydrase inhibitor methazolamide (100 microM). Although Na(+)/H(+) exchange (NHE) isoforms 1, 2, and 3 were identified in fPTCs by immunoblotting, administering EIPA (20 microM) to the interstitial and luminal bath solutions had no effect on net SO(4)(2-) secretion by fPTCs with a normal interstitial pH of 7.7. However, EIPA (20 microM) blocked most of the stimulation caused by acidosis when applied to the lumen but not interstitium, demonstrating that induction of brush-border NHE activity is important. In the intact flounder, serum pH dropped 0.4 pH units (pH 7.7 to 7.3, at 2-3 h) when environmental pH was lowered from 7.8 to approximately 4.3. Whereas serum [SO(4)(2-)] was not altered by acidosis, renal tubular SO(4)(2-) secretion rate was elevated 200%. Thus metabolic acidosis strongly stimulates renal sulfate excretion most likely by a direct effect on active renal proximal tubule SO(4)(2-) secretion. This stimulation appears to be dependent on inducible brush-border NHE activity.
Pelis
Ryan M
RM
Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA.
Edwards
Susan L
SL
Kunigelis
Stan C
SC
Claiborne
James B
JB
Renfro
J Larry
JL
D000136:Acid-Base Equilibrium / Q000502:physiology; D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002256:Carbonic Anhydrases / Q000378:metabolism*; D005432:Flounder; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008871:Microvilli / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism*; D013997:Time Factors
D017923:Sodium-Hydrogen Exchangers; D013431:Sulfates; D002256:Carbonic Anhydrases