Vagusstoff

Abstract: The cornerstone of the neurohumoral theory of synaptic transmission (Elliott, 1905; Dixon, 1907) is the ability of nerves to release an active neurotransmitter on stimulation. The experiments of Loewi demonstrated the release of Vagusstoff (later shown to be acetylcholine) or a sympathin (later shown to be epinephrine) on stimulation of frog cardiac nerves and the effect of these substances to slow or accelerate, respectively, a second isolated heart (e.g., Loewi, 1921). These experiments were later applied to the mammalian heart by Rylant (1927), and made more specifically pertinent to sympathetic nerves by Cannon and his colleagues (Cannon and Uridil, 1921; Cannon and Rosenblueth, 1937). These classical experiments in neuropharmacology were essentially the application of sensitive and quite specific bioassays to demonstrate the release of active hormone on stimulation of a peripheral nerve. The identity of neural “sympathin” in mammalian sympathetic neurons (norepinephrine) as the desmethylated congener of the catecholamine originally extracted from the adrenal gland (e.g., Abel, 1899) (epinephrine) was suspected in the 1920s and 1930s (e.g., Bacq, 1934), but depended on the application of suitable quantitative biochemical and bioassay methods for its definitive demonstration, notably by von Euler (1946).

Abstract: IT is now just over half a century since Otto Loewi provided the first conclusive evidence of the humoral, or chemical, transmission of nerve impulses, a concept that had been suggested by DuBois-R...

Abstract: The action of acetylcholine at muscarinic receptors on excitable tissues has profoundly influenced the development of ideas on chemical transmission. Much of the early progress was the result of the availability and long historical use of belladonna alkaloids. In experiments never published, carried out in 1906, Dixon showed that atropine blocked the inhibitory effect on the exposed frog heart of an extract partially purified from the heart of a dog under vagal inhibition (Dale, 1934). In 1921, Loewi of Graz in Austria reported his experiments on the effects of vagusstoff, providing convincing evidence for chemical transmission. However, even in those long ago days, it was clear to some that the muscarinic actions of esters of choline were not uniformly inhibitory; Sir Henry Dale was “struck by the remarkable fidelity with which [acetylcholine] reproduced the various effects of parasympathetic nerves, inhibitor on some organs and augmentor on others” (Dale, 1934).

Abstract: This paper is concerned with some of the events in physiology that followed Otto Loewi's description of a substance that he named "Vagusstoff"; events that led eventually to the establishment of acetylcholine as a transmitter substance in the nervous system. Much of the work achieving this recognition of acetylcholine as a neurotransmitter took place in the middle third of the twentieth century; a period that witnessed the dislocation of many people as a result of National Socialist policies in Germany, that country's expansionist conquests, and the Second World War. A few of the people who were obliged to emigrate from Europe played prominent roles in these discoveries. This paper describes some of their achievements and, in a way, pays tribute to them.