CHAPTER VII 



Autonomic neuroefFector transmission 



U. S. V O N E U L E R I Department of Physiology, Faculty of Medicine, Stockholm, Sweden 



CHAPTER CONTENTS 



Development of the Concept 

 Anatomical Considerations 

 Humoral Versus Electrical Transmission 

 T'^e Adrenergic Nerve Transmitter 

 dentification 

 Occurrence, Biosynthesis and Storage of Adrenergic Nerve 



Transmitter 

 Release 



Influence of stimulation frequency 

 Effects on remote organs 

 Stimulation of isolated nerves 

 Exhaustibility 

 Removal of Transmitter 

 Possible Adrenergic Nerve Transmitters Other Than Norepi- 

 nephrine 

 The Cholinergic Nerve Transmitter 

 Identification 



Occurrence, Biosynthesis and Storage 

 Release in Organs 



Release from isolated nerves 

 Removal of Transmitter 

 Mechanism of Action of Neurotransmitters 

 Neurotransmitters in Blood and Urine 



DEVELOPMENT OF THE CONCEPT 



THE IDEA OF CHEMICAL TRANSMISSION of nerve im- 

 pulses was apparently first expressed by Elliott (41) 

 who in 1904 suggested the possibility that when the 

 sympathetic nerve impulse reached the target cell it 

 caused an action by liberating epinephrine "on each 

 occasion when the impulse arrives at the periphery." 

 This hypothesis was based on the similarities in action 

 of epinephrine and sympathetic nerve activity, 

 irrespective of whether the action was activation or 

 inhibition. 



Elliott's idea, although representing an entirely 

 new concept, must have struck many as plausible, and 

 it was not surprising that thinking should proceed 



along similar lines. Thus Dixon & Hamill (36) ap- 

 plied the idea to parasyinpathetic nerves, comparing 

 their action with that of muscarine, and after this 

 time it became primarily a matter of skillful experi- 

 mentation to prove the correctness of the theory and 

 to carry the new concept to general acceptance. This 

 task proved more difficult than was perhaps antici- 

 pated. It was chiefly due to the precision of observa- 

 tion and judgment of Dale (25) and the ingenious 

 experimentation of Loewi (83) that the postulate of 

 chemical transmission became tran.sformed into an 

 accepted concept. Acetylcholine gradually moved into 

 the center of interest as a possible candidate for 

 parasympathetic nerve transmission. In Dale's paper 

 concerning the action of injected acetylcholine, he 

 stated that it caused "pronounced vagus-like inhibi- 

 tion of the heart, and various other effects of stimu- 

 lating nerves of the cranial and sacral divisions of the 

 autonomic system — secretion of saliva, contraction of 

 the oesophagus, stomach and intestine and of the 

 urinary bladder." 



The direct experimental proof was provided by 

 Loewi (83) who showed that the fluid collected from 

 an isolated frog's heart during vagus stiinulation 

 inhibited a second heart (fig. i). The effect of the 

 "Vagusstoff" was annulled by atropine and in a large 

 series of experiments it could be shown that the 

 liberated substance behaved in every respect, phar- 

 macologically and chemically, like a choline ester. It 

 is generally assumed that it is acetylcholine. 



Stimulation of the sympathetic nerves in Loewi's 

 experiments caused the release of a factor which 

 accelerated the heart and had properties similar to 

 those of epinephrine. Chemical transmission of 

 sympathetic nerve impulses was independently dem- 

 onstrated by Cannon & Uridil (21) who found that 

 the stimulation of hepatic nerves increased the rate 

 of the denervated heart and rai^d the arterial pres- 



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