The isolation of endogenous modulators of the affinity of acetylcholinesterase to cholinergic ligands

Abstract

By help of a batchwise affinity chromatography procedure the binding of cholinergic ligands to AChE obtained from caudate nucleus from calf brain was studied. The affinity of edrophonium to a crude as compared to a pure enzyme was about 50 times higher. After addition of material isolated from the crude preparation the enzyme was changed to the high affine form. The dissociation constant of the crude enzyme-edrophonium complex determined in the affinity chromatographic experiments was 1.5 X 10(-5) M and in enzymatic experiments 1.8 X 10(-7) M. It is proposed that there is present in mammalian neuronal tissue a factor that increases the affinity of certain cholinergic ligands to a site other than the catalytic site on AChE.

Uptake of Acetylcholinesterase by Neurons in the Substantia Nigra

“…On the other hand, since the post morrem release of AChE is markedly decreased, a similar reduction in secretion of protease (or some other endogenous inhibitor of AChE activity) could account for the observed effects. Certainly, it is known that aminopeptidase is secreted from nigral neurons (Greenfield and Shaw, 1982), and an unidentified endogenous modulator of AChE-ACh binding has been reported in the striatum (Hollunger and Niklasson, 1981). In the present experiments, when exogenous AChE was added to the nigral perfusate, the chemiluminescent signal obtained was the same as that of the same concentration of the enzyme in unperfused medium; it would therefore appear that no comparable modulatory substance is present in the nigral perfusate.…”