2l8 



HANDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOGY I 



argument is further that single stimuli are not capable 

 of eliciting contractions. Whether the negative results 

 of stimulating the denervated adrenal medulla (114) 

 can be used as support for the thesis of inexcitability of 

 denervated target cells is open to doubt. 



The inexcitability of autonomic effectors has also 

 been studied by 'chemical denervation,' by use of 

 drugs which block the action of the autonomic nerves 

 on the target cells. Such experiments have been made 

 on the piloerectors after ergotoxin (20) and on the 

 salivary gland cells after chlorpromazine (42). 



It may therefore be concluded that the smooth mus- 

 cle cell lacks the ability to respond to direct electrical 

 stimulation. Since there is ample evidence to show 

 that these cells respond readily to the chemical 

 stimuli which are known to Ije released from the 

 terminal parts of the autonomic postganglionic nerves, 

 there .seems to be no need to postulate electrical 

 transmission for functional reasons. 



For a detailed discussion of the dual theory of 

 chemical and electrical transmission advocated by 

 Monnier & Bacq (100) see Cannon & Rosenblueth 

 (20}. While there is no evidence for electrical trans- 

 mission from the postganglionic autonomic nerve 

 fiber to the effector cell, the situation may be different 

 in the case of autonomic synapses (loi). 



Smooth muscle thus differs fundamentally from 

 skeletal mu.scle in that the latter is rapidly activated 

 by a trigger mechanism requiring direct contact i:)e- 

 tween the nerve fiber and the effector and working on 

 the all-or-none principle. The sustained activity of 

 the smooth muscle appears to operate on the entirely 

 different principle of graded responses (115). More 

 data are required, however, before the activity of the 

 single smooth muscle cell in response to physiological 

 stimuli can be ascertained. 



by biological tests and by colorimetric methods (1^9)- 

 For the identification of the transmitter the differ- 

 entiation from epinephrine became of primary im- 

 portance. On most target cells the actions of epineph- 

 rine and norepinephrine are qualitatively similar, 

 but the relative activity varies from one organ to 

 another. Thus the action of epinephrine may be 

 over one hundred times that of norepinephrine on the 

 rat's uterus and on the fowl's rectal cecum while the 

 two amines ha\e about the same activity on the iso- 

 lated heart. By comparing the actions of the purified 

 extracts containing the neurotransmitter on a series 

 of test preparations it is possible to ascertain whether 

 the relative actions of the unknown compound go 

 parallel with one or the other of the standard sub- 

 stances. Though norepinephrine passed unnoticed 

 by chemical tests in the so-called pure crystalline 

 epinephrine prepared from suprarenals for nearly 

 50 years, the amines are now readily separated by 

 chromatography (73). 



Generally a single pair of test objects showing 

 sufficiently large differences in the activity' ratio be- 

 tween epinephrine and norepinephrine suffice for 

 differentiation between the two amines. Suitable 

 pairs are for instance the cat's arterial pressure and 

 the fowl's rectal cecum. On the former preparation 

 norepinephrine is from i to 5 times more active as a 

 pressor agent than epinephrine, while it has only ' 4 

 to J200 of the activity of epinephrine on the fowl's 

 rectal cecum (fig. 4). 



The virgin uterus of the cat, and the iris are 5 to 10 

 times more sensitive to epinephrine than to norepi- 

 nephrine and may be u.sed for differentiating pur- 

 poses. The rat's uterus under certain conditions is 

 stimulated by norepinephrine and relaxed by epi- 

 nephrine (fig. 5). 



THE ADRENERGIC NERVE TRANSMITTER 



Identification 



As outlined in the introductory section, Loewi's 

 experiments in 1921 supported the idea that the 

 sympathetic (adrenergic) transmitter was epineph- 

 rine-like. The suggestions by Barger & Dale (9), Bacq 

 (4) and Greer, Pinkston, Baxter & Brannon (58) that 

 norepinephrine conformed better with the actions of 

 the sympathetic transmitter than did epinephrine re- 

 ceived little attention until it was shown by von Euler 

 (124) that the adrenergic nerves contained not epi- 

 nephrine but norepinephrine. The identification of 

 the transmitter with le\'o-norepinephrine was proved 



FIG. 4. Effect of epinepfirine (/-adr), norepinephrine (/- 

 nor-adr) and extract of beef splenic nerves (Spl. n.) on the 

 arterial pressure of the cat and on the isolated rectal cecum of 



the fowl. [From von Euler (128).] 



