L-3,4-dihydroxyphenyalanine (L-DOPA) has been believed as merely a precursor of dopamine (DA), and its therapeutic and/or untoward effects mainly occur through its conversion to dopamine. In 1986, we proposed that L-DOPA by itself acts as a neuroactive substance or neurotransmitter. L-DOPA produced pre- and postsynaptic actions even under the inhibition of aromatic L-amino acid decarboxylase (AADC). L-DOPA was released in a transmitter-like manner, in vitro and in vivo from the striatum, the nucleus accumbens and the lower brain stem nuclei such as the nucleus tractus solitarii (NTS). In the NTS, there were tyrosine hydroxylase (TH)-positive, AADC-negative; L-DOPA-positive and DA-negative-neurons i.e. neurons that may contain L-DOPA as an end product. Recently, GPR143, a gene product of ocular albinism 1, was identified as an L-DOPA receptor. Surprisingly, in Gpr-143 gene-deficient (GPR143-KO) mice, responsiveness to phenylephrine (iv), an a1-adrenoceptor (AR) agonist, was attenuated when compared to wild type (wt) mice. We found that GPR143 expressed in vascular smooth muscle cells coupled with a1-AR and enhanced pressor response to sympathetic nerve activities. We also found GPR143-immunoreactivities in Levy's body in the brains of Parkinson's disease (PD) patients, although further studies are needed to elucidate the significance of L-DOPA and its receptor GPR143 in L-DOPA therapy and in pathogenesis of PD.