PMC

Tritiated (³H) materials were placed in the luminal chamber and influx into the abluminal chamber measured. A Mean permeability (μl/min/cm²) (± SEM) of tritiated leucine across brain microvascular endothelial cells (BMECs) from the luminal-to-abluminal chamber of a transwell. Unlabelled (cold) leucine (10 mg/ml), BCH (1 mM) and kynurenine (1 mM) inhibited leucine permeability. B Mean permeability (μl/min/cm²) (± SEM) of tritiated (³H) kynurenine across BMECs from the luminal-to-abluminal chamber of a transwell, which indicated the predominance of an efflux system that was unmasked by self-inhibition (C) and by unlabelled (cold) tryptophan (1 mM) but not unlabelled (cold) Leucine or BCH. D Efflux of kynurenine is mainly independent of LAT1. Tritiated (3H) kynurenine was placed in the abluminal chamber and efflux into the luminal chamber measured. Efflux was easily measured for tritiated (3H) kynurenine with modest inhibition by leucine or BCH. Enhanced efflux by unlabeled (cold) Kynurenine is consistent with an influx arm, but one more easily inhibited even by abluminal kynurenine than the efflux arm. E Diagrammatic summary of the findings of , showing that leucine is able to inhibit transport of leucine, kynurenine and tryptophan into the brain via LAT1 but does not interfere with transport of tryptophan or excess kynurenine from leaving the brain. 3H = tritiated; UL = unlabelled. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.0001

(A) Exposure to kynurenine (100 mg/day; EKyn) from ED 15 to ED 22 raised kynurenine levels in the serum of fetuses on ED 22. Data are the mean ± SEM (ECon: n = 5 litters; EKyn: n = 6 litters). * P < 0.05 vs. control (ECon). (B) Exposure to kynurenine (300 mg/kg/day; AdKyn) from PD 42 to PD 49 raised kynurenine levels in the serum of treated animals on PD 49. Data are the mean ± SEM (n = 7 per group). *** P < 0.001 vs. control (AdCon).

Effect of the admixture of kynurenine and α-BGT on the frequency of PSCs. A, mean frequency of PSCs recorded 1) after 1-h incubation with α-BGT (100 nM), 2) after 1-h incubation with ACSF containing α-BGT (100 nM) followed by 2- to 5-h incubation with α-BGT (100 nM) plus kynurenine (20 μM), or 3) after 1-h incubation with ACSF containing α-BGT (100 nM) followed by 2- to 5-h incubation with α-BGT (100 nM) + kynurenine (200 μM). In each experimental group, the ACSF used to superfuse the slices was the same as that used during the incubation time. Graph and error bars represent mean and S.E.M., respectively, of data obtained from 10 neurons from six rats in α-BGT, six neurons from four rats in α-BGT + 20 μM kynurenine, and six neurons from four rats in α-BGT + 200 μM kynurenine. The effect of admixture of α-BGT (100 nM) + kynurenine (200 μM) is significantly higher than that of α-BGT alone (**, p < 0.01 according to one-way ANOVA followed by Tukey post hoc test). B, graph shows the percentage reduction of PSC frequency in the continuous presence of α-BGT (100 nM), kynurenine (20 μM), α-BGT (100 nM) + kynurenine (20 μM), kynurenine (200 μM), or α-BGT (100 nM) + kynurenine (200 μM). The magnitude of effect of admixture of α-BGT (100 nM) + kynurenine (20 μM) was significantly larger than kynurenine (20 μM) alone and not different from that of α-BGT (100 nM). The effect of α-BGT (100 nM) + kynurenine (200 μM) was significantly larger than that of kynurenine (200 μM) or α-BGT (100 nM) alone. ** and ##, p < 0.01 according to one-way ANOVA followed by Tukey post hoc test.