EFFECT OF PENICILLIC ACID ON ADENOSINE-TRIPHOSPHATASE ACTIVITY IN THE MOUSE

The effect of penicillic acid on mouse tissue ATPase was examined both in vitro and in vivo. Penicillic acid inhibited in vitro the (Na+, K+)-activated ATPase in the 13,000g (B) fraction in a dose-dependent manner with calculated I50 values of 2.5 and 3.3 × 10-5 m for brain and kidney, respectively. Similar inhibition in the microsomal fraction also was observed with I50 values of 6.0 and 1.0 × 10-5 m for brain and kidney tissues, respectively. Brain and kidney (Na+, K+)-ATPase activity also was inhibited by penicillic acid in vivo. An inhibition time response of (Na+, K+)-stimulated ATPase in brain and kidney tissue from mice receiving 80 mg/kg penicillic acid in saline was noted while a dose-dependent effect was demonstrated in the brain microsomal fraction and in the kidney B and microsomal fractions. Mg2+-Activated ATPase activity was not significantly impaired except for oligomycin-insensitive Mg2+-ATPase in the brain B fraction. Thus, in vitro and in vivo results suggested a possible correlation between inhibition of (Na+, K+)-ATPase activity and penicillic acid-mediated toxicity. © 1979.