Inhibition of L-carnitine uptake into primary rat cortical cell cultures by GABA and GABA uptake blockers.

L-carnitine plays a central role in mitochondrial function and is found to be differentially distributed in the brain. We have shown before that the uptake of L-carnitine into cultured rat cortical neurones was temperature-dependent, as well as potently inhibited by factors affecting the sodium gradient as well as by molecules resembling its structure, e.g. D-carnitine, acetyl-L-carnitine and gamma-aminobutyric acid (GABA). GABA was the most potent inhibitor of L-carnitine uptake. In the present study we have found that specific GABA uptake blockers, nipecotic acid, cis-4-hydroxynipecotic (HNA), guvacine, 2,4-diaminobutyric acid (DABA) and NO 711 inhibit L-carnitine uptake even more potently than GABA. However, apart from NO 711, they caused about the same maximal inhibition, 67.4% at 50 microM for guvacine, compared to 60.5% by GABA. NO 711 was extremely potent and blocked 80.5% of the L-carnitine uptake. In contrast, the GABAA receptor agonists, isonipecotic acid and isoguvacine, or the antagonist bicuculline, at similar concentrations (50 microM), did not significantly inhibit the uptake of the L-carnitine. However, bicuculline at relatively high concentration (500 microM) was inhibitory (38%). The GABAB receptor agonist, baclofen, or antagonist, phaclofen, were ineffective, although 5-aminovaleric acid did significantly inhibit uptake at both 50 and 500 microM, causing 22 and 48% inhibition respectively. Like bicuculline, it was not as effective as GABA or the specific GABA uptake blockers. The results indicate that the uptake of L-carnitine by rat cortical neurones occurs in part by a process that can be potently inhibited by GABA and GABA uptake blockers.