The action of local hormones
In order to account for the resemblance between the actions of sympathetic nerves and those of adrenaline, Elliott (1904) suggested that sympathetic nerves might act by liberating adrenaline. Discussing this theory Barger & Dale (1910) came to the conclusion that the actions of sympathetic nerves did not resemble those of adrenaline so closely as they did those of the corresponding primary amine now known as noradrenaline. Loewi’s demonstration that some sympathetic nerves do actually liberate a substance like adrenaline was published in 1921. Cannon & Rosenblueth (1937) obtained evidence that stimulation of the sympathetic nerves in a cat led to the liberation into the blood stream of a variable mixture of two substances. They supposed that one of those substances had purely excitor effects and the other purely inhibitor effects, and they called them sympathin E and sympathin I. The discovery that two substances were involved was an important advance, but it now seems likely that the two substances are adrenaline and noradrenaline, and since neither of these has purely excitor or purely inhibitor effects the terms sympathin E and Sympathin I should be forgotten. The word sympathin is a convenient label for the substances specifically liberated by adrenergic nerves and may perhaps survive with this meaning. The reason for the slow advance of knowledge about these substances is that the quantities available for study are small. The evidence is still almost entirely pharmacological, since no other methods are sensitive enough. The distinction between adrenaline and noradrenaline has depended on the use of parallel quantitative tests using tissues with different values for the ratio of the activities of these two drugs. If the unknown substance is adrenaline it should match the same amount of adrenaline by any test. It was by using this criterion and studying the effect on distant organs of substances liberated into the general circulation that Cannon & Rosenblueth showed that adrenaline was not the only substance liberated. Their results were such as might be produced by the liberation of a mixture of adrenaline and noradrenaline, but they did not adopt this explanation which was first published by Bacq (1933).