Gamma‐aminobutyric Acid Binding in Mammalian Brain: Receptor‐like Specificity of Sodium‐independent Sites

The binding of radioactive gamma‐aminobutyric acid to particulate fractions of mammalian brain was measured by a centrifugation assay, using repeatedly washed and frozen and thawed membranes and sodium‐free assay conditions. Studies of over 30 structural analogues indicated an excellent correlation between inhibition of gamma‐aminobutyric acid binding and activity as agonists or antagonists on gamma‐aminobutyric acid synapses as reported in the neurophysiology literature. In particular, binding was inhibited by low concentrations of the gamma‐aminobutyric acid receptor‐specific drugs muscimol, homotaurine, and isoguvacine, but very poorly by analogues such as 2,4‐diaminobutyric acid and nipecotic acid which specifically inhibit gamma‐aminobutyric acid transport but are inactive on synaptic receptors. Binding was inhibited by the synaptic antagonist bicuculline but not by picro‐toxinin. Thus, these binding sites show the chemical specificity required of physiological receptors for the neurotransmitter gamma‐aminobutyric acid.