IDENTIFICATION OF MAMMALIAN INHIBITORY TRANSMITTERS 347 



be disregarded. Again, the detection of these enzymes is a histochemical 

 problem but the use of enzyme inhibitors, by prolonging the action of both 

 synaptically released transmitter and iontophoretically applied agents, would 

 indicate a similarity between these substances. 



D. DEMONSTRATION OF THE RELEASE OF THE 



TRANSMITTER SUBSTANCE FOLLOWING STIMULATION 



OF THE APPROPRIATE NERVE FIBERS 



Because of the difficulty of stimulating a particular inhibitory pathway in 

 isolation and also of collecting a suitable effluent from the region where the 

 transmitter is released, the requirements for satisfying tliis criterion are 

 formidable. In addition, if enzymes are present for the inactivation of the 

 transmitter, inhibition of these may be necessary before detectable amounts 

 of the substance could be collected. In the spinal cord it appears that inhibitory 

 neurons have short axons (cf. Eccles, 1957) and consequently it is unhkely 

 that such cells could be excited without prior activation of excitatory neurons 

 having synaptic terminals upon them. Consequently, in the event of a per- 

 fusate or an effluent being collected, presumably from veins or possibly from 

 the surface of the tissue, any method of assay would have to distinguish 

 between excitatory and inhibitory transmitters. 



E. DEMONSTRATION THAT THE PHARMACOLOGY OF 



THE SYNAPTIC INHIBITORY PROCESS WAS IDENTICAL 



WITH THAT OF THE APPLIED SUBSTANCE 



The possibility that the inhibition of enzymes responsible for the destruction 

 of transmitter substances might aid in the identification of the chemical nature 

 of these agents has been mentioned above. The identification of acetylchohne 

 as the transmitter at a particular synapse is indicated by the abiUty of d- 

 tubocurarine to block transmission at the junction. As yet, little is known 

 about the pharmacology of central synaptic transmission and, apart from 

 acetylchohne, an excitatory transmitter or Renshaw cells, no other central 

 transmitter has been identified. When administered intravenously, strychnine 

 depresses all forms of synaptic inhibition within the spinal cord (Eccles, 1957; 

 Curtis, 1959) whhout affecting excitatory synaptic action. It has been assumed 

 that strychnine hinders the access of the inhibitory transmitter to the special- 

 ized subsynaptic receptors and in so doing has an action similar to that of 

 curare at cholinoceptive synaptic receptors (cf. Eccles, 1957, 1959). However, 

 the alternative explanation that strychnine prevents the release of the 

 inhibitory transmitter, ahhough unlikely, has not been disproved. If strychnine 

 has a postsynaptic site of action, the blockage of the inhibitory effect of an 

 apphed chemical substance would indicate certain structural similarities 



