Some interactions of L-DOPA and its related compounds with glutamate receptors

L-DOPA is probably a transmitter and/or modulator in the central nervous sy stem (1). L-DOPA methyl ester (DOPA ME) is a competitive L-DOPA antagonist. However, it remains to be clarified whether there exist L-DOPAergic recept ors. In Xenopus laevis oocytes injected with rat brain poly(A)(+) RNA, L-DO PA induced small inward currents with ED50 of 2.2 mM at a holding potential of -70 mV. The currents were abolished by kynurenic acid or CNQX. Similar L-DOPA-currents were seen in oocytes co-injected with AMPA receptors, GluRs 1,2,3 and 4. In brain membrane preparations, L-DOPA inhibited specific bind ing of [H-3]-AMPA with IC50 Of 260 mu M This inhibition was not modified by 200 mu M ascorbic acid, an antioxidant. L-DOPA did not inhibit binding of [H-3]-ligands of MK-801, kainate, DCKA and CGP39653. DOPA ME and L-DOPA cyc lohexyl ester, a novel, potent and competitive antagonist(2), inhibited spe cific binding of [H-3]-MK-801 with respective IC50 Of 1 and 0.68 mM, but el icited no effect on that of the other [H-3]-ligands. With low affinities, L -DOPA acts on AMPA receptors, while competitive antagonists act on NMDA ion channel domain. L-DOPAergic agonist and antagonist may not interact on ion otropic glutamate receptors. DOPA ME-sensitive L-DOPA recognition sites (1) seem to differ from glutamate receptors.