Na+-dependent γ-aminobutyric acid (GABA) transport in the choroid plexus of rabbit

AbstractThe goal of this study was to examine the mechanisms of transport of γ-aminobutyric acid (GABA) in the choroid plexus. Choroid plexus slices from the rabbit were depleted of ATP with 2,4-dinitrophenol. GABA accumulated in the choroid plexus slices in a concentrative manner in the presence of an inwardly-directed Na+ gradient. Uptake occurred in the presence of Cl−; replacement of Cl− with gluconate abolished uptake. SCN−, NO3− or Br− were able to support uptake in the absence of Cl− to a significant extent (80, 68 and 61% of control, respectively). GABA uptake was saturable (Km of 37±8.5 μM, Vmax of 409±43 nmol/g/min). Na+-driven GABA uptake was inhibited by β-alanine (IC50=22.9 μM) and hypotaurine (IC50=21.9 μM) but less potently by nipecotic acid (IC50=244 μM) and hydroxy-nipecotic acid (IC50=284 μM). Betaine, l-(2,4)-diaminobutyric acid, guvacine and 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol were weak inhibitors (IC50>500 μM). GABA inhibited Na+-driven uptake of taurine (IC50=230 μM); taurine, however, did not inhibit GABA uptake (IC50>1 mM). RT–PCR, using degenerate primers for cloned GABA transporters, did not result in the amplification of a band from rat choroid plexus RNA. The location of the choroid plexus in the ventricles of the brain, and its role in the secretion of the cerebrospinal fluid, suggest a role for the choroid plexus Na+-GABA transporter in the disposition of GABA in the brain