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The fate of [14C] l -3,4-dihydroxyphenylalanine (14C-levodopa) in isolated perfused rat hearts has been studied. Seventy per cent of the perfused [14C]levodopa was recovered intact, while 15 per cent was recovered as dopa metabolites. Only 2 per cent of the perfused radioactivity was retained by the heart tissue. Deaminated derivatives accounted for the majority of the metabolites (7.2 per cent of perfused dose) although 3-O-methyl dopa was found in substantial quantities (1.6 per cent). The absence of significant tissue accumulation of norepinephrine-14C leads to the speculation that amine synthesis from perfused dopa occurs at an extraneuronal site.

The influence of serotonin on the accumulation and metabolism of [3H]norepinephrine by isolated perfused rat hearts has been investigated. Serotonin, at a concentration of 10−6 M, inhibits the uptake of [3H]norepinephrine. A serotonin concentration of 10−4 M appears to reduce the neuronal norepinephrine storage capacity as well as the neuronal membrane amine transport system. Serotonin (10−5 M) also inhibits the extraneuronal metabolism of [3H]norepinephrine in cocainized hearts similar to adrenergic receptor blockers. It is concluded that serotonin at low concentrations would enhance adrenergic responses by blocking the uptake of norepinephrine, while high concentrations of serotonin would block adrenergic receptors and tissue response to norepinephrine. Diminished neuronal amine storage in the presence of serotonin may lead to a prolonged decrease in response to adrenergic nerve stimulation due to a diminished release of authentic transmitter.