TRANSPORT OF ALPHA-AMINOISOBUTYRIC-ACID ACROSS THE BLOOD-BRAIN-BARRIER STUDIED WITH IN-SITU PERFUSION OF RAT-BRAIN

Transport of alpha-aminoisobutyric acid (AIB) from blood to brain in p entobarbital-anesthetized rats was examined using in situ perfusion. I n situ perfusion with washed sheep red blood cells allowed the precise control of the composition of the perfusate that was necessary for a detailed examination of the transport of AIB. Retrograde perfusion at 4 ml/min through the left external carotid arter with oxygenated, arti ficial blood (hematocrit = 0.3) maintained a normal electroencephelogr am during a 10 min experiment. The perfusate cerebral blood flow, at a value of 1.2 +/- 0.1 ml/g/min, and the perfusate cerebral plasma volu me, at a value of 5.4 +/- 1.9 mu l/g, in the left frontal cortex were within the range of reported in vivo values. The in situe PS product f or AIB (3.8 +/- 0.4 mu l/g/min) was higher than the value observed in vivo. AIB uptake was reduced to the in vivo value by 2 mM phenylalanin e (1.3 +/- 0.3 mu l/g/min) and equally well by a mixture of neutral am ino acids at their normal plasma concentrations but was unaffected by 2 mM methyl-AIB or removal of sodium from the perfusate. A kinetic ana lysis showed that the apparent K-i for pheylalanine inhibition of AIB transport was 19.8 +/- 4.9 mu M. Thus, although AIB has affinity for t he large neutral amino acid carrier in the blood-brain barrier, uptake by this mechanism in vivo is negligible due to competition by other a mino acids in the plasma.