Differential effects of non-steroidal anti-inflammatory drugs on cathepsins D and E from rat spleen.

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  • YAMAMOTO Kenji
    Department of Pharmacology, Nagasaki University School of Dentistry
  • TAKEDA Mitsue
    Department of Pharmacology, Nagasaki University School of Dentistry
  • KATO Yuzo
    Department of Pharmacology, Nagasaki University School of Dentistry

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  • 非ステロイド性抗炎症薬のＣａｔｈｅｐｓｉｎ　Ｄ及びＣａｔｈｅｐｓｉｎ　Ｅにおよぼす影響について
  • ヒ ステロイドセイ コウ エンショウヤク ノ Cathepsin D オヨビ

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Abstract

The reactivity and specificity of commonly used non-steroidal anti-inflammatory drugs (NSAID) towards two major intracellular aspartic proteinases, cathepsins D and E, were investigated. Of the different drugs tested, indomethacin and flufenamic acid were shown to be potent inhibitors of cathepsin D. Sodium salicylate (SA) and aspirin also inhibited cathepsin D, although the apparent inhibition was observed at the concentrations of 5mM or above. The inhibitions by these drugs were pH-dependent. The maximal inhibitory potencies of indomethacin and aspirin against cathepsin D activity were observed at pH values below 4.0, whereas that of flufenamic acid was at pH values above 7.0. The Lineweaver-Burk plots showed that the inhibition of cathepsin D by these drugs was of a non-competitive type. On the other hand, all NSAID tested, except for SA, had no inhibitory effect on cathepsin E. SA alone inhibited cathepsin E at concentrations above 50mM. The inhibition of cathepsin E by SA was of the non-competitive type. Of the three monohydroxy benzoates, the inhibitory potency of the ortho isomer (SA) against cathepsin E was greater than those of the meta and para isomers.

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