A comparison of GABA and beta-alanine transport and GABA membrane binding in the rat brain

It was found that rat brain nerve endings contain a high affinity and Na^- dependent transport system for ³H]β-alanine (³H]β-ala). As determined from Michaelis-Menten plots, the ³H]β-ala K_m was 2.8 × 10^-5 M and the V_max was 0.29 nmol/mg protein/5 min. Under similar incubation conditions the ³H]GABA K_m was 3.8 x 10^-6M and the V_max was 6.3 nmol/mg protein/5 min. The ³H]β-ala and ³H]GABA transport systems were further characterized by determining the IC₅₀ values for a number of compounds. The compounds tested were GABA, β-ala, l -2,4-diaminobutyric acid. DL-3-hyd-roxy-GABA, β-guanidopropionic acid, strychnine, γ-guanidobutyric acid, imidazole-4-acetic acid, DL-proline, bicuculline, L-serine, glycine, l -α-ala and taurine. DABA, dl -3-hydroxy-GABA, β-guanidopro-pionic acid and γ-guanidobutyric acid were more potent inhibitors of ³H]GABA than ³H]β-ala transport. Strychnine, imidazole-4-acetic acid, proline and glycine were between 2 and 6 times more potent inhibitors of ³H]β-ala than ³H]GABA transport. β-Ala, bicuculline, serine, α-alanine and taurine were all markedly more potent (12–150 times) inhibitors of ³H]β-ala than ³H]GABA transport. IC₅₀ values were also determined for the above compounds for the sodium-dependent and the sodium-independent binding of ³H]GABA to both fresh and frozen brain membranes. In general, the potency of these compounds to inhibit either sodium-independent or sodium-dependent binding was greater in fresh tissue. It was also observed that the neurophysiologically‘glycine-like’amino acids were more potent inhibitors in the presence of NaCl. No significant correlations were found between ³H]GABA binding under any condition and ³H]GABA or ³H]β-ala transport into nerve endings.