Anticholinesterases / W.D.M. Paton.

  • Paton, William D. M.
Date:
[1954?]
Catalogue details

Licence: In copyright

Credit: Anticholinesterases / W.D.M. Paton. Source: Wellcome Collection.

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    mission, unless the accumulation of transmitter went to excess and began itself to cause synaptic block. Given these facts of cholinergic transmission and apprecia¬ ting the importance of an enzyme for destroying acetylcholine once released (to allow independent repeated shocks, and to prevent block by accumulation) then one might expect to describe the situation in the following simple terms: (1) there would be a single enzyme whose action is specific to acetylcholine and which acts on acetylcholine with great rapidity and in high dilution; (2) this enzyme would be localized at the sites of acetyl¬ choline action only: (3) the enzyme would be specifically antagonized by a num¬ ber of inhibitors which resemble the transmitter chemically; (4) the effect of these inhibitors of the enzyme would all be due to the accumulation of unhydrolysed acetylcholine and the intensity of their effects would be in proportion to the degree of enzyme inhibition. As a framework for the discussion we shall take each of these simple statements in turn, and see how far they have come to need expansion or qualification. The Enzymes Destroying Acetylcholine It was quite early recognized that more than one enzyme in the body could destroy acetylcholine. Since these observations were made, a considerable literature has grown up, a good deal of which is concerned with what the enzymes should be called (for reviews see Augustinsson (1942) and Whittaker (1951) ). This has tended to make the subject rather confusing, but it can be simplified somewhat if one relates each proposed nomenclature to the particular point of interest of the investigator concerned. First was Mendel and Rudney, who studied two crude enzymes both of which could at first split aliphatic esters as well as choline esters. When they purified these preparations, how¬ ever, they found that one ceased to hydrolyse the aliphatic esters, while the other continued to do so. O11 the basis of this and other evidence they concluded that the first enzyme was really and truly concerned with hydrolysing acetylcholine so