Transport of L‐carnitine in isolated cerebral cortex neurons

Abstract

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 (K i 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 b-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cortex neurons (K. A. Naøe Îcz, D. Dymna, J. E. Mroczkowska, A. Broe Èr, S. Broe Èr, M. J. Naøe Îcz and R. Cecchelli, unpublished results), together with the insensitivity of carnitine accumulation towards betaines, implies that a novel transporting protein is present in these cells.

Metabolic approach of absence seizures in a genetic model of absence epilepsy, the GAERS: Study of the leucine‐glutamate cycle

“…The integrity of the cells was controlled by means of the trypan blue test (0.5% in saline). This neuronal preparation contains mostly neurons, as verified by the presence of gammaenolase and GABA transporter GAT1 (Wawrzenczyk et al, 2001), whereas no astroglial markers, such as glial fibrillary acidic protein (GFAP; Wawrzenczyk et al, 2001) and carbonic anhydrase (Wawrzenczyk et al, 1995), were detected.…”

l-Carnitine protects mammalian cells from chromosome aberrations but not from inhibition of cell proliferation induced by hydrogen peroxide

“…Recent reports have also suggested that carnitine has additional pleiotropic functions in tissues that are not considered lipogenic, such as brain. Indeed, in isolated neuronal cells it has been reported that carnitine administration affects differentiation and prevents glutamate neurotoxicity [18,19]. The neuroprotective role of carnitine has also been shown in the rat model of 3-nitropropionic acid-induced mitochondrial dysfunction, which shows a decrease in neuronal ATP levels [20] and in NGF-differentiated pheochromocytoma cells treated with methamphetamine [21].…”

High Affinity Carnitine Transporters from OCTN Family in Neural Cells

“…Carnitine was shown to accumulate in cultured [4] and isolated neurons [5,6], a process reported to be inhibited by a structurally similar compound-a neurotransmitter c-aminobutyric acid (GABA). Although presence of GABA caused an almost twofold increase of K m for carnitine accumulation, this observation reflected rather an effect on carnitine metabolism, in particular on carnitine acetyltransferase [5], especially that GABA transporters expressed in Xenopus laevis oocytes did not transport carnitine [6].…”