410 ANNALS NEW YORK ACADEMY OF SCIENCES 



the assumption that ACh may have the same function there as in 

 other nerves. 



The oxidation products of amino acids, i.e., a-keto acids, have a 

 strong inhibitory effect on the formation of ACh, when present in con- 

 centrations of 10-^ to 10"* M. So far, pyruvic, phenylpyruvic, oxy- 

 phenyl pyruvic acid, and a-keto glutaric acid have been tested.^^' •'*° 



ACh formation has also been studied in extracts prepared from 

 peripheral nerve fibers, in order to determine whether or not choline 

 acetylase is present in the peripheral fibers, as well as in brain. •■'^' ^* 

 This should be the case, if the new concept of the role of the ester in the 

 axon is correct. It has been found that choline acetylase may be ex- 

 tracted from peripheral nerve fibers, as well as from brain. The rate 

 of formation of ACh in extracts prepared from the sciatic nerve of the 

 rabbit was found to be 70 to 90 /xg. per gram and hour. The sciatic 

 contains a large amount of inactive tissue (connective tissue, fat, and 

 myelin). On the assumption that this tissue forms about two-thirds 

 of the total weight, which is a conservative estimate, the amount of 

 ACh which can be formed in the axon of the rabbit sciatic may, thus, 

 be about 250 fxg. per gram per hour, and is probably higher. 



It appeared of special interest to determine the activity of choline 

 acetylase during degeneration, and to test how this metabolism is re- 

 lated to the nerve function, i.e., to conductivity. Conduction is still 

 maintained two days after section, whereas, after three days, it has 

 disappeared. If the release of ACh is responsible for conductivity, 

 formation of ACh should be possible at a rate not too far below normal, 

 as long as the nerve is capable of conducting. 



Forty-eight hours after the section of the sciatic, choline acetylase 

 activity has decreased only about 20 to 25 per cent. After seventy- 

 two hours, when conductivity has disappeared, the decrease is marked, 

 but still about one-third of the enzyme is present. The results are 

 consistent with the assumption that enzyme mechanism is required for 

 conduction. 



C. Nerve Action Potential and Inhibition of Cholinesterase 



In a third line of investigation, cholinesterase activity and nerve 

 action potential could be directly correlated in experiments on the 

 peripheral axon. One of the essential facts in support of the theory 

 of "neuro-humoral" or "synaptic" transmission was the observation 

 that ACh, when applied to synaptic regions, may have a stimulating ac- 

 tion. No action has yet been obtained with the ester, when applied 

 to the axon. Lorente de N6^^ kept bullfrogs' sciatic nerve in a two 



