ZAPA, a substrate for the neuronal high affinity GABA uptake system in rat brain slices

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The GABA analogue ZAPA, a potent GABA A receptor agonist, is a substrate for the GABA high affinity neuronal uptake system. ZAPA was labelled with 14C at a specific activity of 53 mCi/mmol by synthesis from [ 14C]thiourea. [ 14C]ZAPA was taken up into rat cortical slices having an affinity for the carrier about one third that of GABA (ZAPA K m 89 μM; GABA K m 26 μM). ZAPA uptake could be inhibited by the relatively selective GABA neuronal uptake inhibitor, nipecotic acid, but not by the relatively selective glial uptake inhibitor, β-alanine. Specific binding of [ 14C]ZAPA (0.3 μM) to GABA receptor sites was observed only under GABA A conditions with 23% of the total binding being displaced by 1 mM GABA. ZAPA would need to be labelled to higher specific activity to enable a more extensive study of its binding interactions with GABA A receptors.