ACTION OF ANTICHOLINESTERASES, DRUGS AND INTERMEDIATES ON RESPIRATION AND ELECTRICAL ACTIVITY OF THE ISOLATED FROG BRAIN

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Abstract
The isolated frog brain (and nerve) were used to study the effect of several substances on its function, as indicated by O2 consumption and cholinesterase activity. Na and methyl fluoroacetates (NaFA and MFA), inhibitors of carbohydrate metabolism, and the fluorophosphates (diisopropyl fluorophosphate, DFP), poly-phosphate esters (tetraethyl pyrophosphate, TEP), eserine, and atropine, recognized as acting on the acetylcholine-cholinesterase (ACh-ChE) system, affect the function and metabolism in comparable ways, not in different ones. At concns. in each case (except eserine sulfate or salicylate) which alter electrical activity, respiration is inhibited 20-50% (about 50% when electrical waves are abolished) but ChE inhibition may be absent or nearly complete. Results with these drugs, caffeine, and ACh are tabulated. There is no summation of the actions of TEP and MFA or of TEP and ACh. Eserine can largely or fully protect brain and nerve from DFP depression of both function and respiration. Atropine does not protect against TEP or DFP nor is its own action prevented by them. Caffeine in small doses increases electrical activity and O2 consumption, in larger doses depresses both. Inhibitors combined with caffeine similarly increase or decrease function and respiration in parallel at appropriate concns. Fumarate can protect against MFA action and it, with several other dicarboxylic acids at low concns. (glutamic, alpha-ketoglutaric, oxalacetic, aspartic, and succinic; valine, pyruvate and glucose are inert) are able to initiate large convulsive potentials in the isolated brain. These effects were variable. The evidence favors a significant role of the tricar -boxylic acid cycle in brain metabolism, one related to the maintenance of function. The results on frog brain and nerve as well as those in the literature on rats and other animals, indicate that DFP and TEP disturb function by mechanisms independent of the simple inhibition of ChE. An interference with oxidative metabolism is indicated.