NA-DEPENDENT GAMMA-AMINOBUTYRIC-ACID (GABA) TRANSPORT IN THE CHOROID-PLEXUS OF RABBIT()

The goal of this study was to examine the mechanisms of transport of g amma-aminobutyric acid (GABA) in the choroid plexus, Choroid plexus sl ices 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 upta ke. 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). G ABA uptake was saturable (K-m of 37 +/- 8.5 mu M, V-max of 409 +/- 43 nmol/g/min). Na+ -driven GABA uptake was inhibited by beta-alanine (IC 50 = 22.9 mu M) and hypotaurine (IC50 = 21.9 mu M) but less potently b y nipecotic acid (IC50 = 244 mu M) and hydroxy-nipecotic acid (IC50 = 284 mu M). Betaine, L-(2,4)-diaminobutyric acid, guvacine and 4,5,6,7- tetrahydroisoxazolo[4,5-c]pyridin-3-ol were weak inhibitors (IC50 > 50 0 mu M). GABA inhibited Na+ -driven uptake of taurine (IC50 = 230 mu M ); taurine, however, did not inhibit GABA uptake (IC50 > 1 mM). RT-PCR , using degenerate primers for cloned GABA transporters, did not resul t in the amplification of a band from rat choroid plexus RNA, The loca tion of the choroid plexus in the ventricles of the brain, and its rol e 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. (C) 1997 Elsevier Science B.V.