Anticholinesterases / W.D.M. Paton.

  • William Paton
Date:
[1954?]
Catalogue details

Licence: In copyright

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

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    also be identified in the cholinergic electric organ of Electro- phorus, in cholinergic nerves, in autonomic ganglia (chiefly but not only localized in the preganglionic nerve terminals), in the adrenal medulla, in the central nervous system (particularly the basal nuclei) as well as in ganglia in the intestine. These sites are reasonable; within nervous tissue, particularly in the brain, its presence can be taken as a sign (along with choline-acetylase activity, and the presence of acetylcholine itself) of cholinergic activity by the nerves in which it is found. But it is less easy to understand why an enzyme conforming accurately to true cholinesterase should also exist in two nerve-free tissues, the placenta and the red cell, as well as in such unexpected materials as cobra venom (Koelle, 1951; Whittaker, 1951). Pseudo-cholinesterase has a wider, indeed almost universal, distribution. Our simple picture of an enzyme being localized only at the sites of acetylcholine released must therefore be modified; and we have instead to think of ‘true’ cholinesterase being localized at cholinergic synapses in the way expected, but also of true cholinesterase also occurring in other places, and of pseudo¬ cholinesterase being distributed very widely indeed (for reasons still not understood). A number of suggestions about the role of the latter can be made; if, as Professor Burn has suggested, acetylcholine is concerned in spontaneous rhythmic activity of tissues such as heart muscle, then pseudo-cholinesterase might have some important non-synaptic role there. Or secondly, it may be that pseudo-cholinesterase Tacks up’ the true enzyme, particularly if (as Koelle (1953) points out) it can help the latter when high concentrations of acetylcholine occur. But it is much too early to discuss this in detail. The Inhibitors of Cholinesterase A useful way of summarizing these is to relate pharmacological action to their structural resemblance to acetylcholine (Fig. 1). I[t is now believed (largely from Nachmanssohn, Wilson and pergmann’s work on Electrophorus esterase) that the molecule of liicetylcholine reacts with the enzyme at least at two sites: an Lnionic site, negatively charged, which associates with the
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