Interactions of taurine and structurally related analogues with the GABAergic system and taurine binding sites of rabbit brain

1 The aim of this study was to find taurinergic compounds that do not interact with brain GABA ergic systems. 2 Washed synaptic membranes (SM) from whole rabbit brain were able to bind [H-3]muscimol. Saturation experiments of the binding of [H-3]GABA to GABA(B) receptors showed that SM possess two binding components; twice Triton X-100-treated SM contained 0.048mmol endogenous taurine/ kg protein and bound [H-3]taurine in a saturable manner (K-d = 249.0+/-6.3 nm and B-max = 3.4+/-1.0 pmol mg(-1) prot). 3 Among the 19 structural analogues of taurine, 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide (TAG), 2-aminoethylarsonic (AEA), 2-hydroxyethanesulfonic (ISE) and (+/-)cis-2-aminocyclohexane sulfonic acids (CAHS) displaced [H-3]taurine binding (K-i=0.13, 0.13, 13.5 and 4.0 mum, respectively). These analogues did not interact with GABA(A) and GABA(B) receptors and did not affect taurine- and GABA-uptake systems and GABA-transaminase activity. 4 3-Aminopropanesulfonic acid (OMO), beta-alanine, pyridine-3-sulfonic acid, N,N,N-trimethyltaurine (TMT), 2-(guanidino)ethanesulfonic acid (GES), ethanolamine-O-sulphate, N,N-dimethyltaurine (DMT), taurine and (+/-)piperidine-3-sulfonic acid (PSA) inhibited [H-3]muscimol binding to GABA(A) receptors with different affinities (K-i=0.013, 7.9, 24.6, 47.5, 52.0, 91.0, 47.5, 118.1 and 166.3 muM, respectively). Taurine, 2-aminoethylphosphonic acid, DMT, TMT and OMO inhibited the binding of [H-3]GABA to GABA(B) receptors with K-i's in the muM range (0.8, 3.5, 4.4, 11.3 and 5.0, respectively). GES inhibited taurine uptake (IC50 = 3.72 muM) and PSA GABA transaminase activity (IC50 = 103.0 muM). 5 In conclusion, AEA, TAG, ISE and CAHS fulfill the criteria for taurinergic agents. British Journal of Pharmacology (2003) 138, 1163-1171. doi:10.1038/sj.bjp.705134.