Differential Effects of Anti-Inflammatory Agents on Lysosomal Cysteine Proteinases Cathepsins B and H from Rat Spleen

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The reactivity and specificity of commonly used anti-inflammatory agents with lysosomal cysteine proteinases cathepsins B and H purified from rat spleen have been investigated. Of the different agents tested, flufenamic acid and indomethacin were known to be potent inhibitors of cathepsin B. A half-maximal inhibition of the activity of cathepsin B was achieved at drug concentrations of 7.6×10^-5 M of flufenamic acid and 4.0×10^-4 M of indomethacin. The inhibition by these two agents was of a non-competitive type with benzyloxy-carbonyl-phenylalanyl-arginine-4-methyl-7-coumarylamide (Z-Phe-Arg-MCA) as a substrate. The maximal inhibitory potencies of these agents for the cathepsin B activity were observed at pH 7.0. At pH values between 4.5 and 6.5, the inhibitory potencies were less than at pH 7.0. No preincubation time was needed for the reaction between these agents and cathepsin B. In contrast, cathepsin H was not affected by these two drugs even at the drug concentration of 10^-3 M at pH values between 4.5 and 8.0. Other anti-inflammatory agents including aspirin, sodium salicylate, phenylbutazone and prednisolone were found to be poorly or scarcely inhibitory for both cathepsins B and H.