Effects of phenoxybenzamine on the uptake and metabolism of noradrenaline in the rat heart and vas deferens.

1. In the isolated rat heart perfused with various concentrations of (+/-)-(3)H-noradrenaline ((3)H-NA) the addition of phenoxybenzamine, cocaine or desipramine to the perfusion medium resulted in an inhibition of (3)H-NA uptake which appeared on kinetic analysis to be of a competitive nature.2. Phenoxybenzamine also blocked the formation of labelled metabolites of (3)H-NA in the heart at all perfusion concentrations of (3)H-NA; this effect appeared to be unrelated to the inhibition of the neuronal uptake of NA produced by phenoxybenzamine, since no blockade of (3)H-NA metabolism was produced by cocaine in similar experiments.3. In slices of rat vas deferens incubated with various concentrations of (3)H-NA, cocaine and desipramine and phenoxybenzamine were also shown to act as competitive inhibitors of NA uptake. Cocaine and phenoxybenzamine were less potent inhibitors of uptake in the vas deferens than they were in the heart; desipramine was equally potent in both tissues.4. When vas deferens slices were incubated in a medium containing phenoxybenzamine for 30 min before the addition of (3)H-NA, the resulting inhibition of (3)H-NA uptake was increased and changed to a non-competitive type of interaction.5. In hearts or vasa deferentia taken from animals pretreated in vivo with phenoxybenzamine (20 mg/kg), a significant inhibition of (3)H-NA uptake was found when the tissues were exposed to low concentrations of (3)H-NA but not when higher concentrations of (3)H-NA were used.