Blood-brain barrier to H3-γ-aminobutyric acid in normal and amino oxyacetic acid-treated animals

Distribution of radioactivity was examined in various tissues following the administration of H3-γ-aminobutyric acid, injected intraperitoneally to adult mice and intraventriculariy to adult rabbits. In mice treated with amino oxyacetic acid, a potent inhibitor of γ-aminobutyrate-a-ketoglutarate transaminase, no significant amount of radioactivity was found in brain after intraperitoneal injection of labeled γ-aminobutyric acid. After intraventricular injection of labeled γ-aminobutyric acid to rabbits similarly treated, small amounts of radio activity did appear in liver and blood, but electrophoretic characterization showed that the label was not in γ-aminobutyric acid itself but in other metabolites. In untreated mice and rabbits, in which metabolism of γ-aminobutyric acid occurred normally, the label from injected H3-γ-aminobutyric acid was found by electrophoresis to be distributed over several major metabolites. The radioactivity that seemed to move into or from brain in these untreated animals was largely attributable to these labeled metabolites. These labeled derivatives of γ-aminobutyric acid, at present unidentified except glutamine, were discussed. The present results demonstrate that the blood-brain barrier in adult animals is impermeable to both blood-borne γ-aminobutyric acid and endogenous cerebral γ-aminobutyric acid.