LOCALIZATION AND ACTIVITY OF RENAL CARBONIC-ANHYDRASE (CA) IN CA-II DEFICIENT MICE

被引:58
作者
BRECHUE, WF [1 ]
KINNESAFFRAN, E [1 ]
KINNE, RKH [1 ]
MAREN, TH [1 ]
机构
[1] MAX PLANCK INST SYST PHYSIOL,W-4600 DORTMUND,GERMANY
关键词
CARBONIC ANHYDRASE; URINARY ELECTROLYTE; RENAL ACIDIFICATION; METHAZOLAMIDE; (MOUSE); BRUSH-BORDER; INHIBITION; MEMBRANES; KIDNEY; CELLS;
D O I
10.1016/0005-2736(91)90187-D
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A null allele at the mouse Car 2 locus was induced by ethylnitrosourea; mice homozygous for the new allele lack the carbonic anhydrase (CA)-II isoenzyme. The expression of this genetic lesion was investigated by: (1) using tissue fractionation techniques to determine localization and activity of CA in the kidney, and (2) examining renal response to CA inhibition in CA-II deficient mice (CAD), in normal (N) mice and in heterozygous litter mates (LM). N and LM mice had CA activity in proximal tubule brush border membranes and cytosol. CA activity was also localized to membranes and cytosol of the outer medullary region. CAD mice lacked cytosolic activity but had normal CA activity in all membranes examined. All membrane associated CA had 2-8-fold lower sulfonamide sensitivity than cytosolic CA. These inhibition characteristics suggest that the membrane enzyme is CA-IV. Baseline urinary excretion of Na+, K+, and HCO3- was similar in all groups. Urine pH and Cl- excretion were higher and titratable acid output was lower in CAD mice. Inhibition of CA (methazolamide, 25 mg/kg) led in all groups to equivalent increments of urine pH, urine flow, and HCO3-, Na+, and K+ excretion. Cl- excretion was unchanged. Thus the extent of the genetic deficiency of CA-II mice extends to the kidney cytosol but does not alter membrane localization or levels of CA, probably CA-IV. The similar response to CA inhibition in CAD mice suggests that CA-IV, the membrane bound isoenzyme is the important isoenzyme in proximal tubule HCO3- reabsorption.
引用
收藏
页码:201 / 207
页数:7
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