QUANTITATIVE ASPECTS OF THE REPLACEMENT OF NOREPINEPHRINE BY DOPAMINE AS A SYMPATHETIC TRANSMITTER AFTER INHIBITION OF DOPAMINE--HYDROXYLASE BY DISULFIRAM

¹ Department of Experimental Medicine, F. Hoffmann-La Roche & Co. Ltd., Basle, Switzerland

Rats and cats were pretreated with disulfiram (four doses of 400 mg/kg) over a period of 44 hr. In one group of experiments, the norepinephrine and dopamine content of various sympathetically innervated organs was determined and compared with that of controls. In a second group, the amount of dopamine and norepinephrine appearing in the venous effluent of the isolated perfused spleen of the cat after sympathetic nerve stimulation was compared with the content of these amines in the corresponding spleens homogenized at the end of the stimulation period. In cats and rats disulfiram decreased the norepinephrine content and increased the dopamine content in all organs studied. Dopamine only incompletely replaced the missing norepinephrine. Together with data of other authors this suggests that the affinity of dopamine for storage sites is weaker than that of norepinephrine. In tile isolated perfused cat spleen dopamine and norepinephrine were liberated by sympathetic nerve stimulation in the same proportion in which they were stored in the sympathetic nerves of the spleen. These findings are discussed in the light of the hypothesis that transmitter liberation occurs by expulsion of the entire content of storage vesicles.

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