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 |
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Authors: | Sebastianelli Luca Ledonne Ada Marrone Maria Cristina Bernardi Giorgio Mercuri Nicola B |
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Affiliation: | a Clinica Neurologica, Università degli Studi di Roma “Tor Vergata”, Viale Oxford 81, 00133, Roma, Italy b Experimental Neurology Lab, IRCCS “Fondazione S. Lucia”, Via del Fosso di Fiorano 64, 00143, Roma, Italy |
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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. |
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Keywords: | Dopamine smallcaps" >l-dopa Parkinson's disease smallcaps" >l-type amino acid transporters System L BCH Electrophysiology |
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