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

Abstract

L-DOPA is probably a transmitter and/or modulator in the central nervous system (1). L-DOPA methyl ester (DOPA ME) is a competitive L-DOPA antagonist. However, it remains to be clarified whether there exist L-DOPAergic receptors. In X enopus laevis oocytes injected with rat brain poly(A) + RNA, L-DOPA induced small inward currents with ED 50 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 AMP A receptors, GluRs1,2,3 and 4. In brain membrane preparations, L-DOPA inhibited specific binding of [ 3H]-AMPA with IC 50 of 260 μM. This inhibition was not modified by 200 μM ascorbic acid, an antioxidant. L-DOPA did not inhibit binding of [ 3H]-ligands of MK-801, kainate, DCKA and CGP39653. DOPA ME and L-DOPA cyclohexyl ester, a novel, potent and competitive antagonist (2), inhibited specific binding of [ 3H]-MK-801 with respective IC 50 of 1 and 0.68 mM, but elicited no effect on that of the other [ 3H]-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 ionotropic glutamate receptors. DOPA ME-sensitive L-DOPA recognition sites (1) seem to differ from glutamate receptors.