Uptake of [14C]urea by the in vivo choroid plexus--cerebrospinal fluid--brain system: identification of sites of molecular sieving.

1. The time course of the uptake of [(14)C]urea by the lateral ventricular choroid plexus of the adult rat in vivo was analysed to delineate further the permeability characteristics of the epithelial membrane of this secretory tissue.2. Eight hours after I.P. injection, [(14)C]urea attained a steady-state distribution in 78% of the tissue water of lateral ventricular choroid plexus; similarly, approximately 8 hr was required for radiourea to reach a steady-state concentration in both the cerebral cortex and cerebrospinal fluid (c.s.f.).3. Results obtained for compartment analysis were used to calculate the concentration of [(14)C]urea in the epithelium of the lateral ventricular plexus during the approach to and at steady-state distribution. Even after 1 hr of distribution, the [(14)C]urea concentration in choroid cell water was less than 15% of that in plasma water.4. Although the concentration of radiourea in choroid cell water continually increased after 3 hr, it remained in equilibrium with the concentration of [(14)C]urea in c.s.f. water. At the steady state (i.e., 8 hr), the distribution of [(14)C]urea between the water of plasma and that of the choroidal epithelium was considerably away from equilibrium (i.e., by 25-30%).5. An analysis of the concentration gradients for [(14)C]urea across both the apical (c.s.f.-facing) and basolateral (plasma-facing) membranes of the epithelium of the lateral ventricular plexus suggests that the movement of urea is hindered to a greater extent by the basolateral membrane than by the apical membrane.6. Only a single half-time component (1.3 hr) can be resolved from analysis of the curve describing the time course of uptake of radiourea by the choroid epithelial cell compartment.7. The concentration gradient data suggest that urea penetrates from blood to c.s.f. via the choroid plexus by a transcellular pathway; however, it is not possible to rule out a paracellular pathway for urea movement.8. At the steady state, radiourea distributes into 88% of the water of cerebral cortex. This observation, together with the finding of a steady-state concentration gradient for [(14)C]urea from cortical tissue to c.s.f., constitutes evidence that urea movement is hindered at the blood-brain barrier as well as at the blood-c.s.f. barrier.