Ca^<2+> Enhancement of Hemolysis Induced by the Topical Anesthetic Oxethazaine in Vitro

概要

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Oxethazaine (OXZ), a potent topical anesthetic, was found to induce red blood cell (RBC) lysis in vitro, depending upon concentrations of OXZ, RBC and Ca^<2+>. In a 2% RBC suspension, 100 μM OXZ caused almost complete hemolysis in the presence of 1.3 mM Ca^<2+> with only a minimal effect in its absence, while higher concentrations of OXZ (400 μM<) produced hemolysis without Ca^<2+>. The hemolysis induced by OXZ plus Ca^<2+> was poreceded by a rapid increase in ^<45>Ca^<2+> uptake by RBCs, with both the hemolysis and Ca^<2+> uptake being inhibited by 1 mM CoCl_2,NiCl_2,and quinine. Together with the Ca^<2+> influx, rapid influx of Na^+ and efflux of K^+ occurred, and an increasing external K^+/Na^+ concentration ratio inhibited both hemolysis and Ca^<2+> influx. Morphologically, OXZ plus Ca^<2+> caused rapid transformation to spheroechinocytes, the formation of blebs and the pinching-off of blebs, whereas OXZ alone produced membrane invagination. SDS-PAGE analysis of the ghosts prepared from the RBCs treated with OXZ plus Ca^<2+> revealed derangement of cytoskeletal components. OXZ is a rate drug that exhibits a Ca^<2+> ionophore-like action, increasing the Ca^<2+> permeability of plasma membranes.
1998-12-15