Metabolic acidosis regulates rat renal Na-Si cotransport activity.
Recently, we cloned a cDNA (NaSi-1) localized to rat renal proximal tubules and encoding the brush-border membrane (BBM) Na gradient-dependent inorganic sulfate (Si) transport protein (Na-Si cotransporter). The purpose of the present study was to determine the effect of metabolic acidosis (MA) on Na-Si cotransport activity and NaSi-1 protein and mRNA expression. In rats with MA for 24 h (but not 6 or 12 h), there was a significant increase in the fractional excretion of Si, which was associated with a 2.4-fold decrease in BBM Na-Si cotransport activity. The decrease in Na-Si cotransport correlated with a 2.8-fold decrease in BBM NaSi-1 protein abundance and a 2.2-fold decrease in cortical NaSi-1 mRNA abundance. The inhibitory effect of MA on BBM Na-Si cotransport was also sustained in rats with chronic (10 days) MA. In addition, in Xenopus laevis oocytes injected with mRNA from kidney cortex, there was a significant reduction in the induced Na-Si cotransport in rats with MA compared with control rats, suggesting that MA causes a decrease in the abundance of functional mRNA encoding the NaSi-1 cotransporter. These findings indicate that MA reduces Si reabsorption by causing decreases in BBM Na-Si cotransport activity and that decreases in the expression of NaSi-1 protein and mRNA abundance, at least in part, play an important role in the inhibition of Na-Si cotransport activity during MA.
Puttaparthi
K
K
Department of Internal Medicine, University of Texas Southwestern Medical Center and Department of Veterans Affairs Medical Center, Dallas, Texas 75216, USA.
Markovich
D
D
Halaihel
N
N
Wilson
P
P
Zajicek
H K
HK
Wang
H
H
Biber
J
J
Murer
H
H
Rogers
T
T
Levi
M
M
D000138:Acidosis / Q000378:metabolism*; D000643:Ammonium Chloride / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001158:Arteries; D001639:Bicarbonates / Q000097:blood; D001790:Blood Physiological Phenomena; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D027682:Cation Transport Proteins; D004032:Diet; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008871:Microvilli / Q000378:metabolism; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077003:Sodium Sulfate Cotransporter; D013431:Sulfates / Q000652:urine; D027981:Symporters
D001639:Bicarbonates; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D012333:RNA, Messenger; D000077003:Sodium Sulfate Cotransporter; D013431:Sulfates; D027981:Symporters; D000643:Ammonium Chloride