Abstract
The competitive α and β adrenoceptor antagonist labetalol, in concentrations up to 10 −4 M, produced a dose dependent increase in overflow of 3H and [ 3H]noradrenaline in the isolated blood perfused cat spleen following stimulation of the splenic nerves at a frequency of 10 Hz. Labetalol had no effect on the pattern of overflow of label following stimulation. In experiments in which the metabolism of [ 3H]noradrenaline released on nerve stimulation was examined, labetalol produced a concentration dependent increase in the percentage of [ 3H]noradrenaline and a decrease in the percentage of [ 3H]DOPEG in the venous blood following nerve stimulation. Production of [ 3H]COMT metabolites and [ 3H]DOMA was not affected. It is suggested that in the isolated blood perfused cat spleen labetalol produces the elevation of overflow and effects on noradrenaline metabolism by inhibition of neuronal uptake of noradrenaline. The drug has no detectable effects on the enzymes MAO or COMT or on extraneuronal uptake.
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