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.