Gamma-Aminobutyric Acid Binding to Receptor Sites in the Rat Central Nervous System

[(3)H]Gamma-aminobutyric acid (GABA) binds to synaptic membrane fractions of rat brain in a selective fashion representing an interaction with postsynaptic GABA receptors. Inhibition of [(3)H]GABA binding by a variety of amino acids closely parallels their ability to mimic the synaptic inhibitory actions of GABA and does not correlate with their relative affinity for the presynaptic synaptosomal GABA uptake system. [(3)H]GABA binding is saturable with an affinity constant of about 0.1 muM. The GABA antagonist bicuculline inhibits [(3)H]GABA binding with half maximal effects at 5 muM, whereas it requires a concentration of 0.5 mM to reduce synaptosomal GABA uptake by 50%. In subcellular fractionation experiments [(3)H]GABA binding is most enriched in crude synaptic membranes. [(3)H]GABA binding is greatest in the cerebellum, least in the spinal cord and medulla oblongatapons, with intermediate values in the thalamus, hippocampus, hypothalamus, cerebral cortex, midbrain, and corpus striatum.