Taurine modulation of the benzodiazepine-gamma-aminobutyric acid receptor complex in brain membranes.

In unwashed brain membranes taurine produced an inhibition of [3H]flunitrazepam [( 3H]FNZ) binding with IC50 ranging between 31.5 and 11.9 microM; the IC20 varied between 18 and 26 nM. This inhibitory effect was of a mixed type, with a reduction in Bmax and an increase in KD. Various precursors and metabolites of taurine have a less inhibitory effect. Taurine also has little inhibitory effect (IC50 above 500 microM) on the binding of [3H]ethyl-beta-carboline-3-carboxylate. In extensively washed membranes, 10(-5) M taurine produces a 16-21% increase in the binding of [3H]FNZ while 10(-5) M gamma-aminobutyric acid (GABA) increases it between 31 and 42%. However, if 10(-5) M GABA plus 10(-5) M taurine is included in the assay there is a dramatic inhibitory effect. Taurine causes an inhibition of the GABAergic enhancement of [3H]FNZ binding with an IC50 between 7.3 and 7.8 microM. Binding experiments with [3H]taurine done under different conditions failed to detect a Na+-independent and specific [3H]taurine receptor. These results suggest that endogenous taurine, the second most abundant free amino acid in brain, may play an important modulatory role in the GABA-benzodiazepine receptor complex.