AUTONOMIC NEUROEFFECTOR TRANSMISSION 



219 



0.2 ng 0.2 (IF, 0.1 ug 0.2 |ig 



Koradr. Adr. Ijore.dr. Adr. 



FIG. 5. Rat uterus, 3 hours post partum. o.i and 0.2 Mg 

 norepinephrine stimulates, 0.2 Mg epinephrine inhibits the 

 uterus. [From GreetT & Hokz (56).] 



It has been observed for some time that although 

 the actions of epinephrine on the arterial pressure of 

 the cat may be reversed by antisympathomimetic 

 substances (ergotoxine, yohimbine, benzodioxane, 

 dibenamine, phentolamine), the effects of sympa- 

 thetic nerve stimulation are at the most weakened or 

 annulled but never reversed. The explanation was 

 obtained when it was observed that the action of 

 norepinephrine on the arterial pressure is not re- 

 versed but only diminished by doses which reverse 

 the action of epinephrine. This difference has been 

 utilized for the classification of the adrenergic neuro- 

 transmittor both in vitro (124, 129) and in vivo (20, 48). 



The identification has subsequently been con- 

 firmed by other methods, notably by paper and 

 column chromatography, allowing separation from 

 other catechol amines and characterization by 

 specific color or fluorescence reactions. Extracts of 

 heart yield fractions on column chromatography 

 which show the same R-value as pure norepinephrine 

 and the same biological actions (55)- A particularly 

 good source of the adrenergic transmitter is the 

 splenic nerves, from which norepinephrine can be 

 separated by column chromatography and identified 

 by location and by analysis of the active fractions 

 (fig. 6). Venous blood from the spleen collected dur- 



ing stimulation of the adrenergic nerves contains 

 practically pure norepinephrine (98, 108). 



The effects of reflex activation of sympathetic 

 nerves as well as the effects of direct nerve stimulation 

 show all the characteristics of norepinephrine actions 

 (9. 48, 52, 58)- 



The release of an active substance on stimulation 

 of the nerves to an organ does not necessarily mean 

 that this substance is the corresponding chemotrans- 

 mitter. In the experiments of Loewi in 1921 it is likely 

 that the effects observed were due to released epineph- 

 rine, for which good evidence was obtained later (84, 

 124). There is no evidence, however, that epineph- 

 rine serves as adrenergic nerve transmitter in any 

 animal. In the frog the spleen contains chiefly nor- 

 epinephrine (105), and it can not be excluded that 

 the epinephrine released on sympathetic nerve stimu- 

 lation originates from chromaffin cells and not from 

 adrenergic nerve endings. In such a case the substance 

 released from the heart (which lacks coronary vessels 

 in the frog) is not a neurotransmitter proper and the 

 mechanism involved would be analogous to the re- 

 lease of epinephrine from the suprarenals on stimula- 

 tion of its preganglionic nerves. 



Although the theory of Cannon and Rosenblueth 

 concerning the two sympathins is chiefly of historical 

 interest is may be briefly outlined here. [For a de- 

 tailed discussion see Cannon & Rosenblueth (20), 

 and Rosenblueth (113).] According to this theory 

 epinephrine is the adrenergic nerve transmitter, which 

 on reaching the target cells combines with some 



20 25 30 



NUMBER OF TUBE 



FIG. 6. Column chromatogram of extract of beef splenic 

 nerves after adsorption on aluminium oxide and elution, show- 

 ing a maximum for norepinephrine. [From von Euler & 

 Lishajko (132).] 



