Nioka S, Henry R P, Forster R E
Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia 19104-6085.
J Appl Physiol (1985). 1988 Nov;65(5):2236-44. doi: 10.1152/jappl.1988.65.5.2236.
The rate of exchange of 18O between alveolar CO2 and lung water was measured in isolated perfused guinea pig lungs to quantify carbonic anhydrase (CA) activity. The average lung CA activity, with a reaction velocity constant of 5.32 +/- 2.2 s-1, is sufficient to accelerate CO2 reactions in lung water by two orders of magnitude over the uncatalyzed rate at 22 degrees C and a PCO2 of 40 Torr. Three sulfonamide inhibitors of CA with different human erythrocyte membrane permeabilities were used to determine the availability of the enzyme to the perfusate. Ethoxzolamide, the most permeable at 0.1 microM (100 times its inhibition constant, of Ki) inhibited 85% of enzyme activity after exposure of the lung for 3 min and 94% of enzyme activity after 30 min, whereas 1.25 microM (320 times its Ki) acetazolamide (1/165 as permeable) only inhibited CA 28% at 3 min and 75% at 30 min. Benzolamide (less than 1/1,000 as permeable) at 4 microM (1,000 times its Ki) inhibited only approximately 17% of control CA activity by 5 min and 48% by 30 min after the start of perfusion. These data indicate the CA available to pulmonary capillary plasma is approximately 10% of the total lung CA activity, in agreement with published measurements on the homogenized lung.
在离体灌注的豚鼠肺中测量肺泡二氧化碳与肺水之间(18O)的交换速率，以量化碳酸酐酶（CA）的活性。平均肺CA活性的反应速度常数为(5.32±2.2 s^{-1})，足以使肺水中的二氧化碳反应在(22^{\circ}C)和(40 Torr)的二氧化碳分压下比未催化的速率加快两个数量级。使用三种对人红细胞膜通透性不同的CA磺酰胺抑制剂来确定酶对灌注液的可用性。乙氧唑胺在(0.1 microM)（其抑制常数(Ki)的(100)倍）时通透性最高，肺暴露(3)分钟后抑制了(85%)的酶活性，(30)分钟后抑制了(94%)的酶活性；而(1.25 microM)（其(Ki)的(320)倍）的乙酰唑胺（通透性为乙氧唑胺的(1/165)）在(3)分钟时仅抑制CA活性的(28%)，(30)分钟时抑制(75%)。灌注开始后(5)分钟，(4 microM)（其(Ki)的(1000)倍）的苯磺酰胺（通透性小于乙氧唑胺的(1/1000)）仅抑制对照CA活性的约(17%)，(30)分钟时抑制(48%)。这些数据表明，肺毛细血管血浆中可利用的CA约占肺总CA活性的(10%)，这与对匀浆肺的已发表测量结果一致。
