The L-amino acid carrier inhibitor 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (BCH) reduces L-dopa-elicited responses in dopaminergic neurons of the substantia nigra pars compacta

It is not yet clear how L-dopa, that is the most effective drug for the treatment of Parkinson's disease, enters into the dopaminergic neurons to be transformed into dopamine. It is suggested that L-dopa is mainly transported into cells by a group Of L-amino acid carriers named System L. Since these carriers are selectively inhibited by 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (BCH), we have applied this compound to electrophysiologically recorded dopaminergic neurons of the rat substantia nigra pars compacta to examine the possible modulation of the effects Of L-dopa by System L. We have observed that BCH reduced, in a concentration-dependent manner, the membrane hyperpolarization/outward current caused by L-dopa. Interestingly, the actions of dopamine were not changed by this System L inhibitor, suggesting that the reducing effects on L-dopa are not due to a BCH-induced unspecific block of dopamine-mediated events. Therefore, our electrophysiological data that an L-type amino acid carrier, possibly System L, is involved in the transport Of L-dopa into dopaminergic neurons. (C) 2008 Elsevier Inc. All rights reserved.