Central and synaptic transmission in the nervous system (pharmacological aspects) / by W.D.M. Paton.

  • Paton, William D. M
Date:
[1958?]
Catalogue details

Licence: In copyright

Credit: Central and synaptic transmission in the nervous system (pharmacological aspects) / by W.D.M. Paton. Source: Wellcome Collection.

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    Reprinted from ANNUAL REVIEW OF PHYSIOLOGY Vol. 20, 1958 CENTRAL AND SYNAPTIC TRANSMISSION IN THE NERVOUS SYSTEM (PHARMACOLOGICAL ASPECTS)12 By W. D. M. Paton Royal College of Surgeons of England, London, England Criteria for Chemical Transmission Across Synapses The swing of the pendulum, by which the theory of chemical transmission has come to assume a dominant role in concepts of central transmission, has continued. The reviewer believes that the transmission process at central nervous synapses may indeed be in principle chemical, and that the role of electrotonic potentials imposed by one neurone on another may be that of modulating the effects of specific chemical substances. But viewed pharmaco¬ logically, the evidence now accepted for central chemical transmission is often weak, certainly weaker than that put forward many years ago to sup¬ port the theory of chemical transmission at neuromuscular or ganglionic synapses, when it was not generally received. The evidence for the latter junctions was essentially as follows:—that the presynaptic neurone could (a) synthesize the transmitter and (b) release it in pharmacologically identifi¬ able form; and that its action on the postsynapticcell should (c) reproduce the specific events of normal transmission, and (d) be antagonized by competitive blocking agents. That there should exist (e) an enzyme destroying the trans¬ mitter is also important, although the significance of its presence in the pre¬ synaptic endings is less clear than when it is found (as at the motor endplate) in close association with the postsynaptic receptor site. For rigorous proof, none of this evidence can be dispensed with; its force lies in its conjunction. Thus the placenta contains acetylcholine; cobra venom and red cells are rich in cholinesterase; and acetylcholine and drugs like it can not only excite sensory and other nerve endings but be antagonized at these sites by d-tubo- curarine or hexamethonium. But at none of these sites is a cholinergic synapse concerned. Enzyme inhibitors also lead to ambiguties. Eserine, for instance, inhibits both true and pseudocholinesterase, has some atropine-like action, and can paralyze transmission in nerve (331). The phosphorous anti¬ esterases inhibit not only cholinesterase but proteolytic enzymes and ali- esterases (235) and may well have a concealed anaesthetic potency (313). To obtain specific effects by the use of drugs, in short, demands as much care and pharmacological insight as the use of stimulating or recording electrodes demands of electrophysiological knowledge and experience. The most decisive evidence for chemical transmission, i.e., collection and identification of the 1 The survey of literature pertaining to this review was completed in June, 1957. 2 In this chapter, subscript i or o denotes respectively intracellular or extracellular concentration of an ion.