The clearances of twelve amino acids from the ventricles during ventriculo-cisternal perfusion in the rabbit have been measured; uptake by the brain was also measured and this permitted the separate computation of loss to brain and loss to blood during the perfusion. Clearance under carrier-free conditions was greater than when a concentration of 5mM unlabeled amino acid was present in the perfusion fluid. Brain uptake was also usually reduced by the presence of unlabeled amino acid due presumably to suppression of accumulation by brain cells. Reduction of transport across the blood-brain barrier would tend to increase brain uptake, and there was some evidence for a balance between the two opposing tendencies. Inhibition of clearance of a given labeled amino acid could be brought about by unlabeled amino acids of different molecular species. In general, the amino acids fell into three categories: neutral, acidic, and basic, and there was some overlap between them; of the neutral amino acids the A- and L-classification of Christensen was valid, although once again there was some overlap. If, during ventriculo-cisternal perfusion of a labeled amino acid, the activity of this labeled amino acid in the blood was raised well above that in the inflowing perfusion fluid, the labeled amino acid continued to be cleared from the perfusion fluid, suggesting uphill transport. On this basis it was suggested that the normally low concentrations of amino acids in the cerebrospinal fluid (CSF), by comparison with those in plasma, were due to an active transport from the CSF to the blood. Substrate-facilitated transport, whereby the penetration of labeled amino acid into the perfusion fluid from blood could be accelerated by adding unlabeled amino acid to the perfusion fluid, or vice versa, was demonstrated.
SUMMARYThe possibility that, in the rabbit, sulfate is actively transported across the choroid plexuses was investigated by ventriculo-cisternal perfusion in the absence and presence of carrier. No evidence for this could be found.Penetration of sulfate from blood to brain and CSF was measured in the intact animal; equilibration was very slow, indicating the presence of high barriers for this solute, but the low steady-state level in the brain, approached in these experiments, was quite consistent with slow passive permeability across the barriers, with free exchange between extracellular fluid and CSF. The clearance of another slowly penetrating solute, creatinine, from the perfusion fluid during ventriculo-cisternal perfusion was comparable with that of sulfate.
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