NEW PHARMACOLOGY ASPECTS RELATED TO CARBONIC ANHYDRASE

制定了一个五重方案，其中心主题是 碳酸酐酶（C.A.），它的化学性质、抑制作用和 某些器官系统，目前未知。 之间的连续性 生物化学和生理学事件被强调。 我们计划研究 如下：I.碳酸酐酶在肌肉、子宫、卵子和 内淋巴的分泌。 这也引出了一些基本问题， 这些器官的生理机能 特别是在肌肉中，我们将研究二氧化碳 酶抑制后的输出;在子宫内着床 在卵中，辐射冠的分散;在内淋巴中， 分泌的速率和特征。 二.我们将研究二氧化碳在 中性分泌物（NaCl）和是否有肾脏H+输出 独立于二氧化碳系统。 三.新的磺酰胺抑制剂组合 将开发脂溶性和水溶性。 药酶研究 将研究动力学，注意“非竞争性”抑制， 三个CA之间的差异同工酶 四.我们希望描述 线粒体CA，以及脑髓磷脂中的酶， Kcat、Km和对磺胺类药物抑制的敏感性。 五、我们计划 为了研究两栖纲动物的气体交换和酸碱平衡， plethodent，缺乏肺和鳃，完全通过呼吸 皮肤 它们也是唯一缺乏红细胞CA的成年脊椎动物。

A five-fold program has been developed in which the central theme is the enzyme carbonic anhydrase (C.A.), its chemistry, inhibition, and role in certain organ systems, presently unknown. The continuity between biochemical and physiological events is stressed. We plan to study the following: I. The role of carbonic anhydrase in muscle, uterus, ova, and secretion of endolymph. This introduces also fundamental questions about the physiology of these organs. Particularly, in muscle we shall study CO2 output after inhibition of the enzyme; in uterus the implantation evironment; in ova the dispersion of the corona radiata; in endolymph the rate and character of secretion. II. We shall study the role of CO2 in neutral secretions (NaCl) and whether there can be renal H+ output independent of the CO2 system. III. New sulfonamide inhibitors combining lipid and water solubility will be developed. Studies of drug-enzyme kinetics will be pursued, with attention ot "uncompetitive" inhibition, and differences between the three C.A. isozymes. IV. We wish to characterize mitochondrial C.A., and also the enzyme in brain myelin, with respect to Kcat, Km, and susceptibility to inhibition by the sulfonamides. V. We plan to study gas exchange and acid-base balance in sub-order of Amphibia, the plethodonts, which lack both lungs and gills, and respire entirely through the skin. They are also the only adult vertebrates that lack red cell C.A.