Pipecolic acid antagonizes barbiturate-enhanced GABA binding to bovine brain membranes.

L-Pipecolic acid, a brain L-lysine metabolite, is found to inhibit GABA binding to bovine synaptic membranes strongly in the presence of hexobarbital (IC50 = 2 X 10(-10)M) or pentobarbital (IC50 = 2 X 10(-9)M), but only slightly (less than 10%) by itself. Longer dialysis increases this binding inhibition. Hill plots indicate heterogeneity of L-pipecolic acid displaceable GABA binding sites. L-Pipecolic acid may be an endogenous ligand acting as a neuromodulator on the GABA receptor ionophore complex, or it may act on its own membrane binding sites exerting an allosteric effect on the GABA receptor complex. This discovery may be useful for further defining pharmacological and biochemical differences between the GABA receptors in the brain.