ABSTRACT
In 1931 Cannon and Bacq reported an increase in the sympathin in the blood stream, as determined by its effects on the heart, following stimulation of the sympathetic nerves to the colon or to the hind quarters (Cannon & Bacq, 1931). Subsequently Jang showed that the responses of several organs to sympathetic nerve stimulation could be potentiated by appropriate concentrations of the adrenergic receptor blocking drugs 933F, yohimbine and ergotoxine (Jang, 1940). That such blocking drugs may enhance the effects of sympathetic nerve stimulation was further elaborated by Holzbauer and Vogt in 1954, who
showed that the responses of the dibenzyline pretreated uterus to exogenous adrenaline were greatly enhanced over control untreated preparations (Holzbauer & Vogt, 1956). However, it was not until 1957 that a thorough analysis was made of this phenomenon whereby alpha adrenergic blocking drugs potentiate the overflow of noradrenaline and the contractile response of organs to sympathetic nerve stimulation. Brown and Gillespie stimulated the sympathetic nerves to the spleen of the cat and determined the amount of noradrenaline in the venous blood during different frequencies of stimulation and in the presence of different alpha adrenergic blocking drugs (Brown & Gillespie, 1957). Following 200 impulses, noradrenaline output could just be detected at 10 Hz, with maximum output occurring at 30 Hz (Fig. 4.3A). They showed that the low level of output of noradrenaline at 10 Hz was not due to the breakdown of the catecholamine by monoamine oxidase. Furthermore the level at 10 Hz could be increased to the high level found at 30 Hz if adrenergic blocking drugs such as dibenamine were present in the perfusion fluid (Fig. 4.3A). This led them naturally to the conclusion that:
The constancy of the output at frequencies between 1 and 30/sec after dibenamine would be explicable on the ground that the dibenamine had prevented the destruction of the transmitter. The known effect of dibenamine is to block the tissue receptors for noradrenaline, and we must conclude therefore that combination with the receptors is a necessary prelude to the destruction and removal of liberated noradrenaline.
