Adrenergic neurotransmitter functions

Chemical neurotransmission as a concept is generally attributed to Elliott 1 (1904) who emphasized the similarity between the action of adrenaline and sympathetic nerve stimulation. The experimental proof was not provided until 1921, however, by the classical experiments of Loewi 2 and by Cannon and Uridil 3. Loewi, working on frogs, correctly concluded that the active-principle in this case was adrenaline. However, he could hardly suspect at that time that the adrenergic neurotransmitter in this species was an exception rather than the rule, and it was only some 25 years later that it became clear that the active substance which serves this function in mammals and most other animals was the nonmethylated homologue of adrenaline (Von Euler 4,5 1946, 1948). A study of extracts of adrenergic nerves, such as the spenic nerves, and of organs supplied by such nerves, revealed certain differences between the active compound in this material and adrenaline, and with the aid of pharmacological tools and by noting certain chemical characteristics it could be identified as noradrenaline. This primary amine, which was synthesized by Stolz 6 in 1904, was independently found in extracts of the suprarenal gland by Holtz et al. 7 (1944/1947). Systematic studies soon revealed that it was present in almost all organs and tissues, with the notable exception of the placenta, which is nerve-free. This suggested that its occurrence in tissues and organs depends on the presence of nerves. Section of the adrenergic nerves to the heart and some other organs and subsequent degeneration caused the noradrenaline content to fall to very low values, or to disappear, which also indicated that it was normally bound to the nerves in the organs. This concept was further supported by the finding that on regeneration of the previously sectioned nerves to the heart the nor-adrenaline content again rose to approximately normal values (Goodall 8). From these observations it became apparent that the noradrenaline content of an organ or a tissue might afford an estimate of its adrenergic nerve supply. This contribution of physiology to anatomy was not entirely of a confirma-tory character, since the methods available in the early fifties hardly allowed a reliable measure of the extent of sympathetic innervation to an organ or part