Distinct patterns of entry of two non-metabolizable amino acids into brain and other organs of infant guinea pigs

Abstract— Entry of 3-¹⁴C] α-aminoisobutyric acid (AIB) and 1-¹⁴C] 1-aminocyclopentanecarboxylic acid (cycloleucine) into the brain and other organs of the infant guinea pig has been investigated in vivo. The entry of ¹⁴C]AIB into brain was markedly restricted in comparison to its entry into other organs. The mean distribution ratio (¹⁴C in tissue water/¹⁴C in plasma water) achieved in brain at 45 min after administration of a pulse of ¹⁴C]AIB was 0.3. All other organs studied concentrated ¹⁴C]AIB from the blood stream, with the greatest uptake occurring in liver and kidney, in which distribution ratios reached values of 5–10. In contrast to AIB, ¹⁴C]cycloleucine entered the brain at a rate approximately the same as that into other organs. Distribution ratios for ¹⁴C]cycloleucine ranged between 0.5 and 2.0 for all organs. During the first few days of postnatal life, there was a sharp increase of concentrative uptake of ¹⁴C]AIB into liver and kidney. The entry of ¹⁴C]AIB into brain remained unchanged during this period. There was a small (35 percent) decrease in the rate of entry of ¹⁴C]cycloleucine into brain during the first 3 days of postnatal life. Since ¹⁴C]AIB is known to be concentrated from the surrounding medium by brain slices in vitro, we concluded that the locus of restriction of the entry of ¹⁴C]AIB into the brain in vivo is at the blood-brain barrier. We hypothesize that this property of the barrier is important in preventing concentrative uptake of pharmacologically active and potentially harmful amino acids by brain tissue.