Saturable disposition of taurine in the rat cerebrospinal fluid.
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.
Chung
S J
SJ
Department of Pharmacy, University of California at San Francisco, USA.
Ramanathan
V K
VK
Brett
C M
CM
Giacomini
K M
KM
D000409:Alanine / Q000494:pharmacology; D000818:Animals; D002831:Choroid Plexus / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D013654:Taurine / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics
D013654:Taurine; D000409:Alanine