AUTONOMIC NEUROEFFECTOR TRANSMISSION 



229 



ration by chromatography and biological estimation 

 on the rat's arterial pressure the following results 

 (expressed as micrograms per heart in 40 min.) were 

 obtained. 



Electrically drisen 

 Xorepinephrine Epinephrine 



Mean: 0.01 ± o.oi 0.08 ± 0.02 



Spontaneously beating 

 Mean: 0.02 ± 0.0 1 0.08 ± 0.02 



These results are of interest since they clearly show 

 that the proportion of epinephrine is far higher than 

 that occurring in extracts of hearts or in the coronary 

 blood plasma after stimulation of cardiac sympa- 

 thetic nerves (129). The reason for the large release 

 of epinephrine in the spontaneously beating heart is 

 obscure, howe\'er. It therefore appears justified to 

 conclude that the epinephrine released probably 

 originates from chromaffin cells. On the other hand 

 the norepinephrine left in an organ after postgangli- 

 onic denervation constitutes such a small part of the 

 total amount found in the organ with its nerves intact 

 that the amount normally released on sympathetic 

 nerve stimulation must come from the adrenergic 

 nerves. Analysis of the urine from adrenalectomized 

 patients has also shown that the amount of epineph- 

 rine is exceedingly small compared with that of 

 norepinephrine (129). Moreover, no increase in the 

 epinephrine output was observ-ed in the adrenalecto- 

 mized patients subjected to tilting head-up which 

 doubled the norepinephrine output. This speaks 

 strongly against the assumption that epinephrine is 

 released from adrenergic nerves in man. Moreover, 

 the epinephrine content of splenic nerves is as a rule 

 extremely low, a fact .suggesting that the small epi- 

 nephrine amounts found in spleen extracts (129) or 

 sometimes in the effluent blood from the spleen after 

 stimulation of its nerves (108) is not part of the 

 neurotransmitter. For a discussion of the adrenoxine 

 theory of Bacq & Heirman (5) the reader is referred 

 to the survey on this subject by the same authors. 



It is clearly a matter of choice whether the epi- 

 nephrine released from chromaffin cells in the tissue 

 upon sympathetic nerve stimulation should be re- 

 garded as a chemical transmitter. If one agrees to 

 that terminology, the release of suprarenal medullary 

 hormones should likewise be called chemical trans- 

 mission. This, however, is apt to cause confusion of 

 the concepts. It must still be left an open question 

 whether the epinephrine-like actions observed upon 



stimulation of sympathetic fibers to the skin (57) are 

 due to a release from chromaffin cells. 



The possibility of dopamine serving as a neurotrans- 

 mitter requires further study. Holtz, Credner & 

 Koepp (66) showed that it occurred normallv in 

 urine. Its formation was explained as an action of 

 /-dopadecarboxylase on dopa. Later dopamine was 

 demonstrated by Goodall (55) in extracts of the 

 suprarenal gland and in extracts of mammalian heart. 



.Since the presence of catechol amines in organs is 

 correlated with their adrenergic nerves or chromaffin 

 cells, it might be expected that the former aLso con- 

 tain dopamine. This has been shown to be the case; 

 dopamine was found in comparatively large amounts 

 in extracts of splenic nerves (i 17). It seems reasonable 

 to assume that the dopamine found in organs is pres- 

 ent in their adrenergic nerves. If this assumption is 

 correct the question arises as to how dopamine is 

 stored and whether it is released upon nerve stimula- 

 tion. Generally the amount of dopamine in an organ 

 is hardly large enough to cause biological efifects 

 comparable to those caused by the norepinephrine. 

 However, the bovine lung contains large amounts of 

 dopamine in comparison with norepinephrine (132), 

 and it cannot be ruled out that dopamine exerts bio- 

 logical actions in this case. After chromatographic 

 separation the amount of dopamine was found by bio- 

 logical and chemical methods to be 0.5 to i fig per 

 gm tis.sue while the norepinephrine was o.oi to 0.03 

 Mg per gm. Since the biological activity of the two 

 substances is approximately in the proportion 50 to 

 100: 1, it is obvious that dopamine may be biologicallv 

 significant in the lung. 



It has been claimed that isopropylnorepinephrine 

 occurs in small amounts in extracts of the adrenal 

 gland (81). Apparently the amounts are too small to 

 permit detection with the usual colorimetric and bio- 

 logical methods, since these give very good agree- 

 ment with the figures for epinephrine and norepi- 

 nephrine. However, it has been reported that it can 

 be separated by chromatographic technic, a certain 

 fraction showing the characteristic biological action 

 of the isopropyl compound. 



It has been reported that, after stimulation of the 

 sympathetic nerves to the lungs, the isopropyl com- 

 pound appears in the effluent blood (82). Chromato- 

 graphic separation of catechol compounds in extracts 

 of up to 1000 gm bovine lungs have failed to detect 

 this fraction, although catechol acetic acid, dopamine 

 and norepinephrine are readily identified (132). 



