Transmitter-like release and pharmacological activities of levodopa

Abstract

Levodopa was released by depolarizing stimuli from rat striata in a transmitter-like manner in vitro and in vivo. Exogenous nanomolar levodopa stereoselectively facilitated the release of dopamine and noradrenaline via presynaptic beta-adrenoceptors in brain slices even under inhibition of aromatic L-amino acid decarboxylase. This facilitation was competitively antagonized by levodopa methyl ester, whereas it was non-competitively antagonized by propranolol. Furthermore, picomolar levodopa stereoselectively potentiated the isoproterenol-induced facilitation of the noradrenaline release. Levodopa methyl ester selectively antagonized this potentiation, while propranolol antagonized both the facilitation by isoproterenol alone and its potentiation by levodopa. The recognition site for levodopa could be differentiated from the carrier proteins for levodopa transport, because nanomolar levodopa methyl ester abolished the levodopa-induced facilitation of the noradrenaline release, whereas a 30 times higher concentration of L-phenylalanine or L-leucine produced no antagonism. Microinjection of levodopa into the nucleus tractus solitarii led to dose-dependent decreases in arterial blood pressure and heart rate in rats in a levodopa methyl ester-sensitive manner. Based on these findings, we propose that levodopa itself is an endogenous neurotransmitter in the CNS.