text: Thanks to Holtz and Blaschko it was clear that animals synthesized noradrenaline. What was needed to attribute a transmitter role to it was proof of its presence in tissues at effective concentrations and not only as a short-lived intermediate. On April 16, 1945, Ulf von Euler of Karolinska Institute in Stockholm, who had already discovered or co-discovered substance P and prostaglandins, submitted to Nature the first of a series of papers that gave this proof. After many bioassays and chemical assays on organ extracts he concluded that mammalian sympathetically innervated tissues as well as, in small amounts, the brain, but not the nerve-free placenta, contained noradrenaline and that noradrenaline was the sympathy of Cannon and Rosenblueth, the ″physiological transmitter of adrenergic nerve action in mammals″. Overflow of noradrenaline into the venous blood of the cat's spleen upon sympathetic nerve stimulation two years later bore out the conclusion. In amphibian hearts, on the other hand, the transmitter role of adrenaline was confirmed.
  The war prevented Peter Holtz and his group in Rostock from being recognized side by side with von Euler as discoverers of the second catecholamine transmitter noradrenaline. Their approach was different. They sought for catecholamines in human urine and found a blood pressure-increasing material Urosympathin that they identified as a mixture of dopamine, noradrenaline and adrenaline. “As to the origin of Urosympathin we would like to suggest the following. Dopamine in urine is the fraction that was not consumed for the synthesis of sympathin E and I. … Sympathin E and I, i.e. noradrenaline and adrenaline, are liberated in the region of the sympathetic nerve endings when these are excited.” The manuscript was received by Springer-Verlag in Leipzig on October 8, 1944. On October 15, the printing office in Braunschweig was destroyed by an airstrike. Publication was delayed to volume 204, 1947, of Naunyn-Schmiedebergs Archiv für Pharmakologie und Experimentelle Pathologie. Peter Holtz later used to cite the paper as ″Holtz et al. 1944/47″ or ″Holtz, Credner and Kroneberg 1944/47″.
  Remembering his and Barger's structure-activity analysis of 1910, Dale wrote in 1953: “Doubtless I ought to have seen that nor-adrenaline might be the main transmitter – that Elliott’s theory might be right in principle and faulty only in this detail. … It is easy, of course, to be wise in the light of facts recently discovered; lacking them I failed to jump to the truth, and I can hardly claim credit for having crawled so near and then stopped short of it.”
  The next step led to the central nervous system. It was taken by Marthe Vogt, a refugee from Germany who at that time worked with John Henry Gaddum in the Institute of Pharmacology of the University of Edinburgh. ″The presence of noradrenaline and adrenaline in the brain has been demonstrated by von Euler (1946) and Holtz (1950). These substances were supposed, undoubtedly correctly, to occur in the cerebral vasomotor nerves. The present work is concerned with the question whether these sympathomimetic amines, besides their role as transmitters at vasomotor endings, play a part in the function of the central nervous tissue itself. In this paper, these amines will be referred to as sympathin, since they were found invariably to occur together, with noradrenaline representing the major component, as is characteristic for the transmitter of the peripheral sympathetic system.″ Vogt created a detailed map of noradrenaline in the dog brain. Its uneven distribution, not reflecting the distribution of vasomotor nerves, and its persistence after removal of the superior cervical ganglia made it ″tempting to assign to the cerebral sympathin a transmitter role like that which we assign to the sympathin found in the sympathetic ganglia and their postganglionic fibers.″ Her assignment was confirmed, the finishing touch being the visualization of the noradrenaline as well as adrenaline and  dopamine pathways in the central nervous system by Annica Dahlström and  with the formaldehyde fluorescence method developed by Nils-Åke Hillarp (1916–1965) and Bengt Falck (born 1927) in Sweden and by immunochemistry techniques.