358 H. MCLENNAN 



Substance P 



The third substance which should briefly be mentioned here is the poly- 

 peptide substance P. Its occurrence and distribution in the brain have been 

 studied by Kopera and Lazarini (1953) and by Amin et al. (1954). In general 

 its distribution resembles that of 5HT, with the addition that significant 

 amounts are to be found in the first neuron of the posterior columns of the 

 spinal cord. 



The effect of intraventricular administration of substance P is not striking. 

 Changes in the rate and depth of respiration have been reported, as well as 

 shght behavioural changes described as "a general inhibition of spontaneity" 

 (von Euler and Pernow, 1956). Zetler (1956) has reported also that substance 

 P caused sedation in mice, and that it antagonized the "central stimulating 

 effects" of strychnine and picrotoxin. His conclusion was that substance P 

 could play a physiological role as a transmitter substance of inhibitory 

 neurons, but the evidence is shght and indirect. 



To summarize : the distributions in the central nervous system of the three 

 substances here considered is very similar, as is also their action upon appli- 

 cation to the brain. The distribution pattern itself would tend perhaps to cast 

 doubt upon the hkeUhood of their partaking in synaptic events, for many 

 areas of the brain appear to be completely lacking in them while the activity 

 of inliibitory neurons is most probably a generahzed one. For none of these 

 compounds, however, have studies been made to elucidate their effects upon 

 the electrical responses of single neurons when they are introduced into the 

 extracellular space, and until that is done no definitive answers can be given. 

 At the moment I should tentatively assign to them all actions as "depressors" 

 rather than as transmitters. The fact that sympathin certainly, and the other 

 two possibly, can function as transmitters of excitation under certain circum- 

 stances of course does not rule out their possible role as inhibitors at other 

 sites. 



y-Aminobutyrylcholine 



The existence of this compound in the brain was demonstrated by Kuriaki 

 et al. (1958). It has been reported to have actions antagonistic to those of 

 acetylchohne in a number of situations — on the isolated mammafian intestine 

 (Kuriaki et «/., 1958); on the isolated sea urchin oesophagus (Florey and 

 McLennan, 1959); and at the mammahan neuromuscular junction (Asano 

 et al, 1960). It has also been reported that y-aminobutyrylchohne acted to 

 reduce evoked potentials in the cerebral cortex (Takahashi et o/., 1958); 

 however, this effect could not be confirmed by Honour and McLennan 

 (1960), and Curtis and Watkins (1960) have found the compound without 

 action on the neurons of the spinal cord. It seems unlikely therefore that it 

 can have a role to play as an inhibitory transmitter. 



