Submitted on December 27, 2004
Accepted on February 24, 2005
Stimulation of renal sulfate secretion by metabolic acidosis requires Na+/H+ exchange induction and carbonic anhydrase
Ryan M. Pelis1, Susan L Edwards2, Stan C. Kunigelis3, James B. Claiborne4, and J. Larry Renfro1*
1 Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA; Mount Desert Island Biological Laboratory, Salisbury Cove, ME, USA
2 Department of Physiology and Pharmacology, James Cook University, Cairns, QLD, Australia; Mount Desert Island Biological Laboratory, Salisbury Cove, ME, USA
3 Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA
4 Department of Biology, Georgia Southern University, Stateboro, GA, USA; Mount Desert Island Biological Laboratory, Salisbury Cove, ME, USA
* To whom correspondence should be addressed. E-mail: larry.renfro{at}uconn.edu.
The acute effect of metabolic acidosis on SO4
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 SO4
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 (CA) inhibitor methazolamide (100 µM).
Although Na+/H+ exchange (NHE) isoforms 1, 2, and 3 were identified in fPTCs by
immunoblotting, administering EIPA (5-(N-Ethyl-N-isopropyl)amiloride; 20 µM) to the
interstitial and luminal bath solutions had no effect on net SO4
2- secretion by fPTCs with a
normal interstitial pH of 7.7. However, EIPA (20 µM) 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 2-3h) when environmental pH was lowered from 7.8 to ~4.3. Whereas serum
[SO4
2-] was not altered by acidosis, renal tubular SO4
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 S4
2- secretion. This stimulation appears to be dependent on
inducible brush-border NHE activity.
