Localization and activity of renal carbonic anhydrase (CA) in CA-II deficient mice.
Localization and activity of renal carbonic anhydrase (CA) in CA-II deficient mice.
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CA-II 缺陷小鼠肾碳酸酐酶 (CA) 的定位和活性。
DOI：
10.1016/0005-2736(91)90187-d
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Thomas H. Maren
中科院分区：
文献类型：
--
作者：
W. Brechue;E. Kinne;R. Kinne;Thomas H. Maren
用乙基硝基脲诱导小鼠car 2位点的一个空等位基因；新等位基因纯合的小鼠缺乏碳酸酐酶(CA)-II同工酶。该基因病变的表达通过以下方法进行研究：(1)使用组织分离技术确定CA在肾脏中的定位和活性；(2)在CA- ii缺陷小鼠（CAD）、正常小鼠(N)和杂合子产仔（LM）中检测肾脏对CA抑制的反应。N和LM小鼠近端小管刷边膜和细胞质中均有CA活性。CA活性也局限于外髓区膜和细胞质。CAD小鼠缺乏细胞质活性，但在所有检查的膜中具有正常的CA活性。所有膜相关CA的磺胺敏感性都比胞质CA低2 - 8倍。这些抑制特征表明膜酶是CA- iv。在所有组中，Na+、K+和HCO3−的基线尿排泄相似。CAD小鼠的尿pH值和Cl -排泄量较高，可滴定酸排泄量较低。CA （methazolamide, 25 mg/kg）的抑制作用导致所有组的尿液pH值、尿流量、HCO3−、Na+和K+排泄均有相当的增加。Cl -排泄量没有变化。因此，CA- ii小鼠遗传缺陷的程度延伸到肾细胞质，但不会改变CA的膜定位或水平，可能是CA- iv。CAD小鼠对CA抑制的类似反应表明，膜结合同工酶CA- iv是近端小管HCO3−重吸收的重要同工酶。
A null allele at the mouseCar 2locus was induced by ethylnitrosurea; 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.
犬肾皮质膜结合碳酸酐酶的动力学和抑制。
DOI：
10.1016/0005-2744(81)90136-4
发表时间：
1981
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Sanyal,G;Pessah,NI;Maren,TH
通讯作者：
Maren,TH