Activation of carbonic anhydrase isozymes.

CA inhibition by sulphanilamide, discovered in England by Mann and Keilin (1940) and its activation by different classes of compounds, reported in Germany by Leiner (1940), although simultaneous, had completely different consequences for CA research. Whereas CA inhibitors (CAIs) were extensively studied in the next decades, leading to a detailed understanding of the catalytic and inhibition mechanisms, but also to several valuable pharmacological agents (Maren, 1967; Supuran, 1994), CA activators (CAAs) constituted a controversial issue immediately after they were first described (Kiese 1941a,b, 1942; Leiner and Leiner, 1941a, b; van Goor, 1948). Thus, activation of crude human red cell enzyme by diverse tissue extracts or by selected pure compounds, such as histamine, amino acids and some purine derivatives has been reported and retracted several times by the above-mentioned and other authors (reviewed by van Goor, 1948; Main and Locke, 1941; Bakker, 1943), without arriving to a clear-cut answer regarding the mere existence of such a class of CA activity modulators. This topic, then, received little attention from the scientific community in the period from 1950 for at least two reasons: (i) the statement by Clark and Perrin (1951) that activators of CA do not exist, and (ii) the idea that the reported activation is not a phenomenon per se, but an artefact generally due to restoration of CA activity possibly lost in the presence of