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

Exp Neurol. 2008 Jul;212(1):230-3. doi: 10.1016/j.expneurol.2008.04.005. Epub 2008 Apr 15.

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.

MeSH terms

  • Amino Acid Transport System L / antagonists & inhibitors*
  • Amino Acid Transport System L / metabolism
  • Amino Acids / metabolism
  • Amino Acids, Cyclic / pharmacology*
  • Animals
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / metabolism
  • Dopamine / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Interactions / physiology
  • Female
  • Levodopa / antagonists & inhibitors*
  • Levodopa / metabolism
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Rats
  • Rats, Wistar
  • Substantia Nigra / drug effects*
  • Substantia Nigra / metabolism

Substances

  • Amino Acid Transport System L
  • Amino Acids
  • Amino Acids, Cyclic
  • Carrier Proteins
  • 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid
  • Levodopa
  • Dopamine