Acetylcholine metabolism in the central nervous system

Abstract

Addition of K+ (0.027[image]) to a medium containing eserine and in which brain slices are respiring brings about a large increase in the rate of formation of acetylcholine. The value may reach 40-50 [gamma] per g. wet weight of tissue. High concs. of K+ inhibit acetylcholine synthesis by brain. The accelerating effect of K+ does not take place in a substrate-free medium and is confined only to the free acetylcholine. The amount of "combined" acetylcholine is either unchanged or diminished. The accelerating action of K+ is neutralized by Ca++ or Mg.++ Rb+ and Cs+ behave similarly to K+. Addition of K+ to minced brain tissue does not stimulate acetylcholine synthesis as markedly as with brain slices. Addition of K+ to either minced or intact brain under conditions where no synthesis is occurring diminishes the amt. of combined acetylcholine and correspondingly increases the free acetylcholine. This takes place anaerobically as well as aerobically. The effect of K+ is to increase the permeability of the nerve cell so that acetylcholine diffuses through the cell membrane faster than in the absence of K+. An equilibrium exists in the nerve cell between free and "combined" acetylcholine. Addition of acetylcholine depresses synthesis of acetylcholine by brain tissue, this only being clearly seen in presence of K+. NH4+ acts similarly to K+ but has a greater secondary inhibitory action on acetylcholine synthesis.