ISOLATION OF ENDOGENOUS MODULATORS FOR THE GABA(A) AND TAURINE RECEPTORS

Several endogenous brain substances which inhibit [H-3]muscimol binding were isolated, and one of them has been purified to apparent homogeneity. The purification involved the extraction of brain tissue with water, followed by several steps of gel filtration column chromatography and high performance liquid chromatography (HPLC). The muscimol binding inhibitor (MBI) thus obtained appeared to be homogeneous as judged from the elution profile of an HPLC column, in which a symmetrical peak was obtained when the eluate was monitored at either 220 or 280 nm. Furthermore, the MBI activity coincided with the absorption peak. The purified MBI is not 7-amino butyric acid (GABA), beta-alanine or taurine since these amino acids are clearly separated from the MBI in the purification procedures. The MBI has no effect on benzodiazepine (BZ) binding or glutamate binding to their respective receptors. However, the MBI is a more potent inhibitor for [H-3]taurine binding than that of [H-3]muscimol binding. The MBI appears to be a small molecule (<2000 Da) that is heat and acid/base stable. The chemical nature of the MBI is currently under investigation.