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Blood‐Brain Barrier Transport of Basic Amino Acids Is Selectively Inhibited at Low pH

Abstract: The transport of amino acids across the blood‐brain barrier was measured with the single‐pass carotid injection method. The pH of the injected bolus varied between 4.5 and 8.5. Arginine and lysine uptakes were inhibited 24% at pH 5.5 and 59% at pH 4.5. The uptakes of 2‐aminobicyclo (2,2,1) heptane‐2‐carboxylic acid and phenylalanine were unaffected at this pH. There were also no changes observed in choline, glucose, or butanol transport. The Ki of arginine transport inhibition by H+ was 2.4 ± 0.5 μM; i.e., pH 5.6 ± 0.1. No change with pH occurred in the Km of arginine transport, while a significant decrease (p < 0.01) was observed in the Vmax (10.2 ± 2.3 nmol min−1 and 5.6 ± 2.3 nmol min−1 g−1 at pH 7.5 and pH 5.5, respectively). This noncompetitive inhibition was found to be transient as arginine uptake at pH 7.5; it was measured by carotid injection 30 sec following a previous bolus which was buffered to pH 4.5, and was not significantly different from the control. This selective inhibition of the blood‐brain barrier basic amino acid carrier demonstrates the advantage of the carotid injection approach in exposing the capillary exchange site to extreme alterations in chemical composition which could not be tolerated systemically.