| 2553987 |
Kaneko M, Lee SL, Wolf CM, Dhalla NS: Reduction of calcium channel antagonist binding sites by oxygen free radicals in rat heart. J Mol Cell Cardiol. 1989 Sep;21(9):935-43.
In view of the importance of Ca2+-channels in controlling the entry of Ca2+ into the myocardium, this study was undertaken to examine the effects of oxygen free radicals on the binding of Ca2+-channel antagonists in rat heart by employing [3H]-nitrendipine as a ligand. Isolated heart membranes were incubated with xanthine + xanthine oxidase (a superoxide anion radicals generating system), hydrogen peroxide (an activated species of oxygen), or hydrogen peroxide + Fe2+ (a hydroxyl radicals generating system). The assay of the [3H]-nitrendipine binding activity revealed that the maximal number of binding sites (Bmax) were reduced in a time-dependent manner by superoxide radicals without any changes in the binding constant (Kd); a significant reduction of Bmax was seen after incubating membranes with xanthine + xanthine oxidase for a 10-min-period. Superoxide dismutase showed a protective effect on the superoxide radicals induced reduction in Bmax. Both hydrogen peroxide and hydroxyl radicals also depressed the Bmax for [3H]-nitrendipine binding without any significant change in Kd; catalase and mannitol showed protective effects on hydrogen peroxide or hydroxyl radicals induced depression in Bmax, respectively. These results indicate that oxygen free radicals may reduce the number of Ca2+-channels in the cell membrane and this change may contribute towards decreasing the voltage-dependent Ca2+ influx in the cardiac cell. |
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