AUTONOMIC NEUROEFFECTOR TRANSMISSION 



12 



0-8 



4 



Frequency (stimuli/eec.) 



J I I L 



I I I I I 





 12 - 



0-8 



20 



40 



60 



80 100 



200 800 



4 



Frequency (per sec.) 



10 



2U 



30 



40 



50 



FIG. lo. --1; Mean output per stimulus of 'sympathin' plotted 

 against the frequency of stimulation. At all frequencies of 

 stimulation the total number of pulses was 2oq. The vertical 

 lines represent the standard errors of the means. Figures for 

 loo, 200 and 300 pulses per sec. are single observations. B: 

 First part of the graph in A with an extended scale for frequency. 

 The individual results from three animals previously given 

 dibenamine are shown. The output per stimulus at 10 pulses 

 per sec. has increased and equals the maximum in the un- 

 treated animal. There is no obvious variation with frequency. 

 [From Brown & Gillespie (14).] 



work on 'sympathin'. While the study of the trans- 

 mitter release in this manner, by recording the effect 

 on sensitized remote target organs, was valuable in 

 the elucidation of the transmission mechanism as 

 such, its physiological significance is doubtful. Even 

 though Cannon and Rosenblueth and their co- 

 workers obtained increases in heart rate, dilatation of 

 the pupil and contraction of the nictitating membrane 

 in denervated organs after stimulation of sympathetic 

 nerves in other parts of the body, the appearance of 

 remote effects caused by transportation of the re- 

 leased transmitter by the blood is by no means a 

 constant phenomenon. 



The failure of some authors (22) to observe remote 

 effects even on the highly sensitized denervated 

 nictitating membrane in spite of intense stimulation 

 of sympathetic nerves has been taken to indicate the 

 presence of peripheral inactivation mechanisms which 

 largely eliminate an overflow of transmitter. How- 

 ever, a physiologically occurring overflow in the 

 meaning of Cannon and Rosenblueth cannot be 

 denied for the following reason. If the catechol amines 

 are estimated in urine from adrenalectomized pa- 

 tients the amounts of epinephrine are very low while 

 the norepinephrine content tends to be even higher 

 than in normal subjects (129). The only possibility 

 for norepinephrine to occur in the urine then is a 

 release from some source in the body other than the 

 adrenals. Since the adrenergic nerves are known to 

 contain large amounts of this transmitter, it appears 

 legitimate to assume that during the incessant ac- 

 tivity of the adrenergic system a certain overflow of 

 transmitter takes place continuously. 



As to the value of the remote effects studied by 

 Cannon and Rosenblueth as a proof of chemotrans- 

 mission from nerves, it should be borne in mind that 

 nervous stimulation might also cause a release from 

 chrornaffin cells present in the tissues. This criticism 

 does not invalidate their conclusions in principle 

 since there is good evidence in some of Cannon and 

 Rosenblueth's experiments that at least some of the 

 effects are due to the release of norepinephrine. 



It is interesting to note that the so-called inhibitory 

 sympathin is obtained when the splanchnics are 

 stimulated but not when the hepatic nerves are stimu- 

 lated (fig. 1 1). It is known that the s£lanchnic_nerves 

 may innervate groups of chromaitiin-cells^at various 

 sites. Their secretory products may then be carried 

 by the blood stream to excite the denervated organ. 

 In case of the hepatic nerves there was only a stim- 

 ulating effect but no inhibitory effect on the dener- 

 vated uterus of the cat, indicating that practically only 

 nore£ine£hrine was released in this case. As far as 

 can be ascertained at the present time this norepi- 

 nephrine is released from adrenergic nerve endings. 



The question whether reflex liberation of the 

 adrenergic transmitter could be large enough to 

 cause actions on remote organs has al.so been studied 

 (80). As a result of afferent sciatic or brachial nerve 

 stimulation it was possible to demonstrate a contrac- 

 tion of the denervated nictitating membrane in the 

 adrenalectomized cat. It has also been possible to 

 show a reflex liberation of the adrenergic transmitter 

 by action on remote organs, for instance after excite- 

 ment and struggle (103). The slower development of 



