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.
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D007700:Kinetics; D046911:Macromolecular Substances; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D011963:Receptors, GABA-A; D013654:Taurine / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000596:Amino Acids; D046911:Macromolecular Substances; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D013654:Taurine; D005680:gamma-Aminobutyric Acid