3,4-dihydroxyphenylalanine (dopa), dopamine and norepinephrine storage in the rat heart after L-dopa-further evidence for norepinephrine release

The storage of 3,4-dihydroxyphenylalanine (dopa), dopamine (DA) and norepinephrine (NE) in the rat heart was studied after the administration of a single dose of L-dopa (100 mg/kg). Endogenous NE concentration was significantly reduced 45 min after L-dopa despite high levels of dopa and DA. Synthesis blockade with disulfiram did not prevent the decline in [³H]NE or endogenous NE induced by DA. Therefore, acceleration of NE synthesis by precursor substrate loading distal to the rate-limiting step in the biosynthetic pathway cannot explain the increased cardiac NE turnover that occurs after L-dopa. Administration of L-dopa resulted in a significant decrease in the retention of tracer [³H]NE in both the particulate and soluble cell fractions without changing the subcellular distribution of [³H]NE. Dopa and DA were recovered from only the soluble fraction of tissue homogenates. The storage of dopa and DA in the heart was unaffected by reserpine pretreatment. The results are consistent with dopa-induced NE release of the type that occurs with indirect acting sympathomimetic amines. The relationship of these findings to autonomic dysfunction in humans after L-dopa is discussed.