Effect of rubratoxin B on adenosine triphosphatase activities in the mouse

Abstract

The effect of rubratoxin B on the ATPase activities in mouse brain, kidney, and liver was examined both in vitro and in vivo. The fraction used contained nerve endings, mitochondria, and endoplasmic reticulum. ATPase activities in brain were inhibited in vitro with ID50 values of 1.17, 2.57, and 8.35 μ m rubratoxin B for Na +K + and oligomycin-sensitive and -insensitive Mg 2+ ATPases, respectively; inhibition in all cases was dose dependent. Kidney ATPases also showed similar dose-dependent inhibition by rubratoxin B in vitro, and the ID50 values were 2.26, 2.10, and 9.12 μ m for Na +K + and oligomycin-sensitive and -insensitive Mg 2+ ATPase activities, respectively. Oligomycin-sensitive Mg 2+ ATPase in liver preparation was inhibited by rubratoxin B with an ID50 of 4.5 μ m. No in vitro inhibition of oligomycin-insensitive Mg 2+ ATPase was observed in the liver preparation. Brain ATPase activities were inhibited at 2 hr after in vivo treatment with rubratoxin B. Na +K + and oligomycin-sensitive Mg 2+ ATPases in brain showed more pronounced sensitivity to the toxin than oligomycin-insensitive Mg 2+ ATPase activity. Similarly, rubratoxin B showed a significant inhibition of liver Mg 2+ ATPases in vivo. These results indicate that ATPase inhibition by rubratoxin B may be involved in the biochemical mechanism for its toxic action.