Abstract-Reuptake of neuroactive amino acids by high affinity transport systems in the CNS is thought to terminate the neurotransmitter activity of these substances. This notion has been challenged since the homoexchange of synaptosomal and exogenous glutam am ate and the corresponding homoexchange of synaptosomal and exogenous GABA has been demonstrated. We reported that depolarizing media (56 mM-KCI, 1 m~-CaCl,) lowers the GABA content of synaptosomes. In such synaptosomes, net and apparent (radioactive) GABA uptake are similar. When rat cortical synaptosomes (1 mg protein/ml) are incubated with 10 p~-['~C]~-glutamate, net and apparent (radioactive) uptake are similar. When the synaptosome levels are decreased to 0.5 mg protein/ml or less, then net uptake becomes a fraction of radioactive uptake (exchange ensues). Net glutam am ate uptake is Na+-dependent and temperaturedependent. Furthermore, a 1 mM concentration of KCI or RbCl supports net L-glutamate and GABA uptake. LiCl, NH,Cl, CsCl and choline chloride are ineffective. In addition. diaminobutyric acid (but not fi-alanine) inhibits net and apparent GABA uptake. The demonstration of net uptake of L-glutamate and GABA by their respective high affinity systems is consonant with the idea that these systems may play a role in neurotransmitter inactivation in the synaptic region
