Transport of L-carnitine in isolated cerebral cortex neurons.
The accumulation of carnitine was measured in cerebral cortex neurons isolated from adult rat brain. This process was found to be lowered by 40% after preincubation with ouabain and with SH-group reagents (N-ethylmaleimide and mersalyl). The initial velocity of carnitine transport was found to be inhibited by 4-aminobutyrate (GABA) in a competitive way (Ki = 20.9 +/- 2.4 mM). However, of various inhibitors of GABA transporters, only nipecotic acid and very high concentrations of 1-[2-([(diphenylmethylene)amino]oxy)ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride (NO-711) acid decreased carnitine accumulation while betaine, taurine and beta-alanine had no effect. The GABA transporters expressed in Xenopus laevis oocytes did not transport carnitine. Moreover, carnitine was not observed to diminish the accumulation of GABA in cerebral cortex neurons, which further excluded a possible involvement of the GABA transporter GAT1 in the process of carnitine accumulation, despite the expression of this protein in the cells under study. The absence of carnitine transporter OCTN2 in rat cerebral cortex neurons (K. A. Nałecz, D. Dymna, J. E. Mroczkowska, A. Broër, S. Broër, M. J. Nałecz and R. Cecchelli, unpublished results), together with the insensitivity of carnitine accumulation towards betaines, implies that a novel transporting protein is present in these cells.
Nencki Institute of Experimental Biology, Department of Molecular and Cellular Neurobiology, Warsaw, Poland.
A
A
Wawrzeńczyk
A
A
Sacher
M
M
Mac
M J
MJ
Nałecz
K A
KA
Nałecz
D000818:Animals; D001622:Betaine / Q000494:pharmacology; D001667:Binding, Competitive; D001693:Biological Transport, Active; D002331:Carnitine / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D005260:Female; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D009474:Neurons / Q000378:metabolism*; D009557:Nipecotic Acids / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D010091:Oximes / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000074058:Solute Carrier Family 22 Member 5; D013654:Taurine / Q000494:pharmacology; D014982:Xenopus laevis; D015091:beta-Alanine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009557:Nipecotic Acids; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D010091:Oximes; C492020:SLC22A5 protein, human; C493413:SLC6A1 protein, human; C493415:Slc6a1 protein, rat; D000074058:Solute Carrier Family 22 Member 5; D015091:beta-Alanine; C078793:NNC 711; D013654:Taurine; C030278:nipecotic acid; D001622:Betaine; D005680:gamma-Aminobutyric Acid; D002331:Carnitine