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Ramanathan, V.K. et al.

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 gamma-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 microM, Vmax of 409 +/- 43 nmol/g/min). Na+-driven GABA uptake was inhibited by beta-alanine (IC50 = 22.9 microM) and hypotaurine (IC50 = 21.9 microM) but less potently by nipecotic acid (IC50 = 244 microM) and hydroxy-nipecotic acid (IC50 = 284 microM). Betaine, L-(2,4)-diaminobutyric acid, guvacine and 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol were weak inhibitors (IC50 > 500 microM). GABA inhibited Na+-driven uptake of taurine (IC50 = 230 microM); 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.[1]

References

Na+-dependent gamma-aminobutyric acid (GABA) transport in the choroid plexus of rabbit. Ramanathan, V.K., Brett, C.M., Giacomini, K.M. Biochim. Biophys. Acta (1997) [Pubmed]

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