Function of proximal tubule carbonic anhydrase defined by selective inhibition.
Function of proximal tubule carbonic anhydrase defined by selective inhibition.
复制标题
通过选择性抑制定义近端小管碳酸酐酶的功能。
DOI：
10.1152/ajprenal.1983.245.4.f443
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发表时间：
1983
期刊：
影响因子：
--
通讯作者：
DuBoseJr,TD
中科院分区：
文献类型：
--
作者：
Lucci,MS;Tinker,JP;Weiner,IM;DuBoseJr,TD
管腔碳酸酐酶在近端小管重吸收碳酸氢盐中的具体作用尚未确定，因为很难选择性地抑制管腔酶而不同时抑制细胞质酶。本实验采用体内微灌注，微量热法，和微电极技术，以确定管腔应用的葡聚糖结合的碳酸酐酶抑制剂（DBI）对碳酸氢盐重吸收率（JtCO 2）和管腔内pH值在大鼠近曲小管的影响。用人工超滤液以20 nl/min灌注肾小管。将无酶抑制剂活性的氨基乙基葡聚糖（AED）加入到对照灌注液中，并测定未与葡聚糖结合的母体抑制剂STZ的作用。DBI和STZ均显著降低JtCO 2，从138 μ g/ml 10 pmol X mm-1 X min-1（对照）分别降至30 μ g/ml 4和30 μ g/ml 9。与对JtCO 2的不可区分的影响相反，在DBI灌注期间靠近灌注部位测量的管腔内pH为6.80 μ g/ 0.02，而STZ灌注的pH为7.24 μ g/0.04（P小于0.001）。使用收集的灌注液总CO2浓度和60 mmHg的肾皮质PCO 2，计算该溶液的平衡pH值为7.27。因此，DBI仅抑制管腔碳酸酐酶。我们的结论是，管腔碳酸酐酶与近端小管液的功能性接触，是必要的，至少80%的碳酸氢盐重吸收由这段。（250字处删节）
The specific role of luminal carbonic anhydrase in bicarbonate reabsorption by the proximal tubule has not been established because it has been difficult to inhibit selectively the luminal enzyme without simultaneous inhibition of the cytoplasmic enzyme. The present experiments employed in vivo microperfusion, microcalorimetry, and microelectrode techniques to determine the effects of luminal application of a dextran-bound carbonic anhydrase inhibitor (DBI) on bicarbonate reabsorptive rate (JtCO2) and intraluminal pH in the rat proximal convoluted tubule. Tubules were perfused at 20 nl/min with an artificial ultrafiltrate. Aminoethyl dextran (AED) with no enzyme-inhibitor activity was added to the control perfusate, and the effects of the parent inhibitor STZ not bound to dextran were also determined. Both DBI and STZ significantly reduced JtCO2 from 138 ⁺/⁻ 10 pmol X mm-1 X min-1 (control) to 30 ⁺/⁻ 4 and 30 ⁺/⁻ 9, respectively. In contrast to the indistinguishable effects on JtCO2, intraluminal pH measured close to the site of perfusion was 6.80 ⁺/ 0.02 during DBI perfusion, whereas with STZ perfusion the pH was 7.24 ⁺/⁻ 0.04 (P less than 0.001). Using the collected perfusate total CO2 concentration and a renal cortical PCO2 of 60 mmHg, the calculated equilibrium pH for this solution was 7.27. DBI inhibited only luminal carbonic anhydrase, therefore. We conclude that luminal carbonic anhydrase is in functional contact with proximal tubule fluid and is necessary for at least 80% of bicarbonate reabsorption by this segment.(ABSTRACT TRUNCATED AT 250 WORDS)