Chung S J, Ramanathan V, Giacomini K M, Brett C M
Department of Pharmacy, University of California, San Francisco 94143.
Biochim Biophys Acta. 1994 Jul 13;1193(1):10-6. doi: 10.1016/0005-2736(94)90326-3.
Taurine, a beta-amino acid, plays an important role as a neuromodulator and is necessary for the normal development of the brain. Since de novo synthesis of taurine in the brain is minimal and in vivo studies suggest that taurine does not cross the blood-brain barrier, we examined whether the choroid plexus, the blood-cerebrospinal fluid barrier, plays a role in taurine transport in the central nervous system. The uptake of [3H]taurine into ATP-depleted choroid plexus from rabbit was substantially greater in the presence of an inwardly directed Na+ gradient, whereas in the absence of a Na+ gradient taurine accumulation was negligible. A transient inside-negative potential gradient enhanced the Na(+)-driven uptake of taurine into the tissue slices, suggesting that the transport process is electrogenic. Na(+)-driven taurine uptake was saturable with an estimated Vmax of 111 +/- 20.2 nmol/g per 15 min and a Km of 99.8 +/- 29.9 microM. The estimated coupling ratio of Na+ and taurine was 1.80 +/- 0.122. Na(+)-dependent taurine uptake was significantly inhibited by beta-amino acids, but not by alpha-amino acids, indicating that the transporter is selective for beta-amino acids. Na(+)-dependent taurine uptake showed some selectivity for anions: the accumulation was comparable in the presence of Cl-, Br- and thiocyanate whereas I-, SO4(2-) and gluconate did not stimulate the uptake significantly. Collectively, our results demonstrate that taurine is transported in the choroid plexus via a Na(+)-dependent, saturable and apparently beta-amino acid selective mechanism. This process may be functionally relevant to taurine homeostasis in the brain.
牛磺酸是一种β-氨基酸,作为神经调质发挥着重要作用,对大脑的正常发育至关重要。由于大脑中牛磺酸的从头合成极少,且体内研究表明牛磺酸无法穿过血脑屏障,我们研究了脉络丛(血脑脊液屏障)在中枢神经系统中牛磺酸转运过程中是否发挥作用。在存在内向性Na⁺梯度的情况下,从兔ATP耗尽的脉络丛中摄取[³H]牛磺酸的量显著增加,而在没有Na⁺梯度的情况下,牛磺酸的积累可忽略不计。短暂的内向负电位梯度增强了Na⁺驱动的牛磺酸向组织切片的摄取,这表明转运过程是电生的。Na⁺驱动的牛磺酸摄取具有饱和性,估计最大摄取速率(Vmax)为每15分钟111±20.2 nmol/g,米氏常数(Km)为99.8±29.9 μM。估计的Na⁺与牛磺酸的偶联比为1.80±0.122。Na⁺依赖性牛磺酸摄取受到β-氨基酸的显著抑制,但不受α-氨基酸的抑制,这表明该转运体对β-氨基酸具有选择性。Na⁺依赖性牛磺酸摄取对阴离子表现出一定的选择性:在Cl⁻、Br⁻和硫氰酸盐存在时积累相当,而I⁻、SO₄²⁻和葡萄糖酸盐不会显著刺激摄取。总的来说,我们的结果表明牛磺酸通过一种Na⁺依赖性、饱和且明显对β-氨基酸有选择性的机制在脉络丛中进行转运。这一过程可能在功能上与大脑中牛磺酸的稳态相关。