Abstract
Choline, a precursor of the neurotransmitter acetylcholine, is synthesized in only small amounts in the brain, so the choline concentration in the brain may vary depending on the plasma concentration and the transport rate across the blood-brain barrier. To elucidate the transport mechanism of choline, we carried out uptake experiments with mouse brain capillary endothelial cells in culture (MBEC4). [3H]Choline uptake was linear for up to 5 min. An examination of the concentration dependence of [3H]choline uptake revealed the operation of both saturable (Jmax = 423+/-27 pmol min(-1) (mg protein)(-1) and Kt = 20.0+/-3.1 microM) and non-saturable (kd = 1.23+/-0.045 microL min(-1)(mgprotein)-1) processes. The saturable process was independent of Na+ and pH, but was dependent on membrane potential as a driving force. Various basic drugs and endogenous substances, including substrates and inhibitors of the organic cation transporter, significantly inhibited the [3H]choline uptake. These data suggest that choline was taken up into the endothelial cells via two routes and that a membrane potential-dependent carrier-mediated transport system may participate in choline transport across the blood-brain barrier.
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