Inhibitory Activities of Metal Chelators on Endothelin-Converting Enzyme. I. In Vitro Studies

概要

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The effects of various metal chelators on endothelin (ET)-converting enzyme (ECE) activity were examined in vitro. Three chelators, 2,3-dimercapto-1-propanol (DMP), toluene-3,4-dithiol (TDT) and 8-mercaptoquinoline (8-MQ), were found to dose-dependently inhibit ECE activity, but this inhibition was much weaker compared with EDTA. In the presence of Zn^<2+>, the inhibitory activity of all these compounds, including EDTA, was abolished. The addition of Ca^<2+> and Mg^<2+> markedly attenuated the inhibitory activity of EDTA, but the other three chelators were still able to inhibit ECE. ECE, once inactivated by EDTA or 8-MQ, was reactivated by the addition of divalent cations such as Zn^<2+> and Mn^<2+>. These compounds also inhibited angiotensin-converting enzyme activity in a manner similar to the inhibition exhibited towards ECE. Chelate-titration indicated that DMP, TDT and 8-MQ chelate Zn^<2+> but not Ca ^<2+> and Mg^<2+>. These results suggest that the ECE inhibition exhibited by these compounds is mainly attributable to their chelating activities. The metal-selective chelating activity by DMP, TDT and 8-MQ may contribute to the retention of ECE inhibition in the presence of Ca^<2+> and Mg^<2+>.
社団法人日本薬学会の論文
1994-02-15