The effects of anticholinesterases on oxidative phosphorylation in brain, and their relation to potassium loss and nerve degeneration

Abstract

The effect of diisopropyl phosphorofluoridate (DFP), eserine and Nu 1250 (a prostigmine analogue) on O2 uptake and CO2 evolution by slices of chicken brain was related to the K loss from the slices induced by these compounds. In every case when K loss has occurred, either O, uptake has been inhibited or CO2 evolution has been stimulated. Concentrations of DFP, eserine and Nu 1250, similar to those which produce K loss from slices, caused an inhibition of oxidative phosphorylation (as measured by P/O ratios) of homogenates of chicken brain. In addition to these inhibitors, the effects of NN''-diiso-propylphosphorodiamidic fluoride (mipafox), NN''-diisopropylphosphoro-diamidic anhydride and tetracethyl pyrophosphate on oxidative phosphorylation were also investigated. The inhibition of oxidative phosphorylation obtained with the 6 anticholinesterases is discussed in relation to the degenerative changes which certain of these compounds produce in the nervous system.