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

Abstract

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.