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.
Sebastianelli
Luca
L
Clinica Neurologica, Università Degli Studi di Roma, Tor Vergata, Roma, Italy.
Ledonne
Ada
A
Marrone
Maria Cristina
MC
Bernardi
Giorgio
G
Mercuri
Nicola B
NB
D027062:Amino Acid Transport System L / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000598:Amino Acids, Cyclic / Q000494:pharmacology*; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D007980:Levodopa / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism
D027062:Amino Acid Transport System L; D000596:Amino Acids; D000598:Amino Acids, Cyclic; D002352:Carrier Proteins; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; D007980:Levodopa; D004298:Dopamine