INHIBITORY TRANSMITTERS — A REVIEW 365 



transmitter, namely Factor I extracts for the mammalian central nervous 

 system and Substance I for crustacean inhibitory neurons, are uncharac- 

 terized as yet. It seems to me possible, however, that some chemical relation- 

 ship to acetylchohne may be a feature of the active ingredient of either or both 

 materials, for it is striking in how many situations the actions of these extracts 

 either antagonize or mimic the effects of applied acetylchohne. This point 

 is brought out by the data of Table 2, in which the interactions of Factor I 

 and of the extracts studied by Pfeifer and Pataky and by Lissak and End- 

 roczi, with acetylchohne are set forth. 



The implication that the "Fs" and acetylchohne are competing for the same 

 receptor sites in these various tissues, sometimes with parallel and sometimes 

 with antagonistic effects, is very strong, and the corollary is that some struc- 

 tural relationship between them may exist. As mentioned earlier the dis- 

 tinction between Factor I and Substance I is one of definition only at present 

 and it may be that the active component of each is identical. The extracts 

 prepared by Lissak and Endroczi and by Pfeifer and Pataky have been less 

 studied but it is evident that they too show anti-acetylcholine properties. 



In conclusion, it is obvious that the search for inhibitory transmitter sub- 

 stances is far from over. The electrical events associated with activation of 

 inhibitory synapses have now been well described for a number of organs, 

 both in vertebrates and in invertebrates, and show considerable similarities 

 in the situations studied. The characteristic change is a transient increase in 

 the polarization of the cell membrane, due to an increased membrane per- 

 meabihty to potassium and/or to chloride ions. These effects are mimicked 

 by Factor I at mammahan motor neurons, by Substance I for peripheral 

 inhibition in Crustacea and by acetylcholine for the vertebrate heart. There is 

 some evidence for beheving that the "I" extracts may owe their activity to a 

 compound related structurally to acetylcholine. It is reasonable to assume 

 that the two nervous tissue extracts, which may or may not owe their activity 

 to the same chemical substance, in fact crntain a transmitter substance active 

 at inhibitory synapses. 



REFERENCES 



Amin, a. H., Crawford, T. B. B. and Gaddum, J. H. (1954) The distribution of Substance 

 P and 5-hydroxytryptamine in the central nervous system of the dog. J. Physiol. 

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Angelucci, L. (1956) Experiments with perfused fro^ "^ spinal cord. Biit. J. Pharmacol. 

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AsANO, M., NoRO, T. and Kuriaki, K. (1960) Inhibitory ac ions of ;'-aminobutyryIcholine. 

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Bazemore, a. W., Elliott, K. A. C. and Florey, E. (1957) Isolation of Factor I. J. 

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BoiSTEL, J. and Fatt, P. (1958) Membrane permeability change during inhibitory trans- 

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