Carrier Mediated Blood‐brain Barrier Transport of Choline and Certain Choline Analogs

Abstract— Blood‐brain barrier (BBB) transport of choline and certain choline analogs was studied in adult and suckling rats, and additionally compared in the paleocortex and neocortex of adult rats. Saturable uptake was characterized by a single kinetic system in all cases examined, and in adult rat forebrains we determined a K m = 442 ± 60 μM and V max = 10.0 ± 0.6 nmol min ‐1 g ‐1 . In 14–15‐day‐old suckling forebrains a similar K m (= 404 ± 88 μM) but higher V max (= 12.5 ± 1.5 nmol min ‐1 g ‐1 ) was determined. When choline uptake was compared in two regions of the forebrain, similar Michaelis‐Menten constants were determined but a higher uptake velocity was found in the neocortex (i.e. neocortex K m = 310 ± 103 μM and V max = 12.6 ± 2.8 nmol min ‐1 g ‐1 ; paleocortex K m = 217 ± 76 μM and V max = 7.2 ± 1.5 nmol min ‐1 g ‐1 ). Administration of radiolabelled choline at low (5 μM) and high (100 μM) concentrations, followed by microwave fixation 60 s later and chloroform‐methanol‐water separations of the homogenized brain did not suggest a relationship between concentration and the appearance of label in lipid or aqueous fractions as observed in another in‐vitro study elaborating two‐component kinetics of choline uptake. It was observed that 60s after carotid injection 12–14% of the radiolabel in the ipsilateral cortex was found in the chloroform‐soluble fraction. Hemicholinium‐3 ( K i = 111 μM), dimethylaminoethanol ( K i = 42 μM), tetraethyl ammonium chloride, tetramethyl ammonium chloride, 2‐hydroxyethyl triethylammonium iodide, carnitine, normal rat serum, and to a lesser extent lithium and spermidine all inhibited choline uptake in the BBB. Unsubstituted ammonium chloride and imipramine did not inhibit choline uptake. No difference was observed in blood‐brain barrier choline uptake of unanesthetised, carotid artery‐catheterized animals, and comparable sodium pentobarbital‐anesthetized controls.