COMMENTS ON THE 

 EXCITINE-INHIBITINE HYPOTHESIS 



Takashi Hayashi 



Department of Physiology, School of Medicine, Keio University, Tokyo 



During and after the second world war, we began to study the mechanism 

 of excitation of muscle and nerve from the standpoint of chemical physiology. 

 The fundamental idea of the mechanism of excitation which we arrived at, 

 was a statement expressed in the following equation: 



excitine-inhibitine _^ excitine -p inhibitine (1) 



(rest) ^~ (excitation) 



The idea was based on our experiments on the "salt contraction" — the 

 long continued spontaneous twitches of an excised skeletal muscle bathed in 

 isotonic sodium chloride solution (Hayashi, 1956). 



The equation (1) means that the excitation of muscle is due to a sudden 

 dissociation of a certain chemical agent at the site of the excitable tissue. The 

 two components of this agent are called "excitine" and "inhibitine". 



In the early phase of our study, we identified the excitine as carnosine 

 (jS-alanyl-L-histidine) and the inhibitine as carnitine (betaine of y-amino-/S 

 hydroxybutyric acid). Since then we succeeded in synthesizing DL-carnitine as 

 well as L-carnosine, and on repeating the early experiments once ascertained 

 that these substances do not have exciting or inhibiting actions by themselves, 

 but that they cause excitation or inhibition if they are mixed with each other 

 at certain ratios (Hayashi, 1960). But now we have to revise it. Carnitine 

 corresponds to excitine, carnosine to inhibitine. If the two combinations are 

 mixed, their actions are neutrahzed and they have no affect on excised muscle. 



The following experimental results were obtained : 



(1) If DL-carnitine in Ringer's solution (0-066-0T47 %) is dropped on to an 

 excised sartorius muscle of toad a sequence of twitches result. If small 

 amounts of glutamic acid, aspartic acid, taurine, cysteine or acetylchoHne are 

 added to the carnitine solution, concentrations of 0-0066-0-0147% of this 

 compound are sufficient to induce muscle contractions. The substances which 

 potentiate the action of DL-carnitine are normal constituents of ordinary 

 vertebrate skeletal muscles. Their concentrations in this tissue are indicated 

 in Table 1. It should be mentioned that they do not cause muscle contractions 

 by themselves. 



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