Effect of antirheumatic drugs on cathepsin B1 from bovine spleen.

The inhibitory effect on cathepsin B1 of 39 antirheumatic and other agents has been studied. The enzyme was purified from bovine spleen (specific activity 2.8 units/ml/E280 unit) and the effect of the drugs measured by determining the decrease of enzyme activity towards BANA as substrate. Analgesics, antimalarials, cytostatic agents, steroids as well as d-penicillamine, colchicine, allopurinol, chlorzoxazone and chlorpromazine either had no effect on cathepsin B1 or inhibited it to a very small extent. Typical anti-inflammatory and antirheumatic agents like gold and pyrazolone derivatives (with the exception of sulfinpyrazone) suppressed the activity of the enzyme at a concentration of 10(-6) M. Two others, indomethacin and diclofenac, suppressed it at a concentration of 10(-5) M. Two sulfonated polysaccharides, arteparon and pentosan polysulfate (SP54), were also potent inhibitors. Salicylates, however, inhibited cathepsin B1 only at much higher concentrations (10(-2) M. Higher concentrations of cysteine (2 mM) decreased the inhibitory effect of some otherwise effective drugs. Inhibition of cathepsin B1 may be one way in which some of the drugs tested exercise their therapeutic effect in rheumatic diseases.