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大鼠脑脊液中牛磺酸的饱和性处置

Saturable disposition of taurine in the rat cerebrospinal fluid.

作者信息

Chung S J, Ramanathan V K, Brett C M, Giacomini K M

机构信息

Department of Pharmacy, University of California at San Francisco, USA.

出版信息

J Pharmacol Exp Ther. 1996 Feb;276(2):676-82.

PMID:8632336
Abstract

Recently, we described a saturable Na(+)-dependent taurine transporter in the choroid plexus, the blood-CSF barrier (Chung et al., 1994). The goal of this study was to determine whether this transporter plays a role in the in vivo elimination of taurine from the CSF. 3H-taurine and 14C-inulin were injected into the lateral ventricle of anesthetized rats, and the concentrations of the radiolabeled compounds in the CSF were determined. The apparent clearance of taurine from the CSF was greater than the estimated CSF bulk flow (P < .005), which indicates that there is a clearance process in addition to the CSF bulk flow. Taurine distribution into the choroid plexus was at least 10-fold higher than that found in other brain areas. The apparent clearance of 3H-taurine and the distribution of taurine into the choroid plexus and cerebral cortex were dose-dependent. The Michaelis-Menten rate constant estimated from the in vivo elimination study (40 +/- 25 microM) is in the range of that obtained for taurine uptake in isolated choroid plexus tissue slices (137 +/- 67 microM). Both alpha- and beta-alanine decreased the clearance of taurine from the CSF as well as the distribution of taurine into the choroid plexus via inhibitory effects (either direct or indirect) on the Na(+)-taurine transporter in the choroid plexus. These data suggest that the previously characterized taurine transporter in the choroid plexus plays a role in the in vivo saturable disposition of taurine in the CSF.

摘要

最近,我们描述了脉络丛(血脑屏障)中一种可饱和的、依赖钠离子的牛磺酸转运体(Chung等人,1994年)。本研究的目的是确定该转运体是否在脑脊液中牛磺酸的体内清除过程中发挥作用。将³H-牛磺酸和¹⁴C-菊粉注入麻醉大鼠的侧脑室,并测定脑脊液中放射性标记化合物的浓度。牛磺酸从脑脊液中的表观清除率大于估计的脑脊液总体流量(P < 0.005),这表明除了脑脊液总体流量外,还存在一个清除过程。牛磺酸在脉络丛中的分布比在其他脑区至少高10倍。³H-牛磺酸的表观清除率以及牛磺酸在脉络丛和大脑皮层中的分布呈剂量依赖性。从体内清除研究估计的米氏速率常数(40 ± 25 μM)与在分离的脉络丛组织切片中牛磺酸摄取所获得的常数(137 ± 67 μM)范围一致。α-丙氨酸和β-丙氨酸均通过对脉络丛中Na⁺-牛磺酸转运体的抑制作用(直接或间接)降低了牛磺酸从脑脊液中的清除率以及牛磺酸在脉络丛中的分布。这些数据表明,先前在脉络丛中鉴定的牛磺酸转运体在脑脊液中牛磺酸的体内可饱和处置中发挥作用。

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