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Transport of valproate and its effects on GABA uptake in astroglial primary culture
M Nilsson1, E Hansson, L Rönnbäck
1Institute of Neurobiology, University of Göteborg, Sweden.
Abstract:
The antiepileptic drug Na(+)-valproate (VPA) is a broadspectrum anticonvulsant. It has been proposed to be involved in the inhibitory mechanisms of GABA-ergic systems. In this study, transport of the drug and possible influence on the GABA uptake were investigated in primary astroglial cell cultures from newborn rat cerebral cortex. The results show a Na+ and K+ independent high affinity uptake for VPA, with km and Vmax not significantly different from those observed for the GABA uptake. In the presence of the drug, the Km-value of the GABA uptake increased. The GABA uptake inhibitors guvacine, (RS)-Cis-4-OH-nipecotic acid and 4,5,6,7-tetrahydroisoxazolo (4,5- c) pyridin-3-ol (THPO) did not influence upon the uptake of VPA, suggesting a transport mechanism for the drug, separated from the GABA uptake carrier.