Proc. West. Pharmacol. Soc 50: 95-97 (2007) Effect of Taurine on the Concentrations of Glutamate, GABA, Glutamine and Alanine in the Rat Striatum and Hippocampus Svetlana M. Molchanova 1 , Simos S. Oja 2 and Pirjo Saransaari 1 * 1 University of Tampere, Medical School, Brain Research Center, FI-33014 University of Tampere, Finland; 2 Tampere University Hospital, The Centre for Laboratory Medicine and Department of Clinical Physiology and Nuclear Medicine, Tampere, Finland *E-mail: pirjo.saransaari@uta.fi ABSTRACT Taurine, a non-protein amino acid, acts as an osmoregulator and inhibitory neuromodulator in the brain. Here we studied the effects of intraperitoneal injections of taurine on the concentrations of glutamate and GABA, and their precursors, glutamine and alanine, in the rat striatum and hippocampus. Injections of 0.25, 0.5 and 1 g/kg taurine led to a gradual increase in taurine tissue concentrations in both hippocampus and striatum. Glutamate and GABA also increased in the hippocampus, but not in the striatum. Glutamine increased and alanine decreased markedly in both brain structures. The results corroborate the neuromodulatory role of taurine in the brain. Taurine administration results in an imbalance in inhibitory and excitatory neurotransmission in the glutamatergic (hippo- campus) and GABAergic (striatum) brain structures, affecting more markedly the neurotransmitter precursors. INTRODUCTION Taurine (2-aminoethanesulphonic acid) is a conditionally essential non-protein amino acid abundant in the central nervous system [1]. It acts as an inhibitory neuromodulator and osmoregulator [2-4]. In vitro, taurine increases neuronal survival under excitotoxic conditions [5-10], and has therefore been considered useful in the treatment of a number of neurodegenerative disorders, including ischemia, epileptic seizures, energy metabolism perturbation and oxidative stress [11-16]. In vivo studies confirming the protective properties of taurine are lacking. As a highly polar and hydrophilic compound, taurine does not readily cross cell membranes. High concentrations of taurine (in the range of grams per kg) may be needed to achieve biologically active concentrations in the brain [17]. Taurine crosses the blood-brain barrier and is taken up into neural cells by means of active carrier- mediated transport systems, which require Na + and Cl - [18-19]. Acute application of taurine attenuates glutamate-evoked depolarization and reduces intracellular Ca 2+ [6,10]. On the other hand, chronic application leads to an imbalance in glutamatergic and GABAergic neurotransmission [20]. The aim of the present study was to monitor the effects of intraperitoneal injections of taurine on the concentrations of the main excitatory and inhibitory neurotransmitters glutamate and γ-aminobutyric acid (GABA), as well as their precursors, glutamine and alanine, in the rat striatum and hippocampus. METHODS The studies were carried out on Sprague-Dawley male adult rats in accordance with the European Community Directive for the ethical use of experimental animals. All efforts were made to minimize both the suffering and the number of animals used. The rats were anesthetized with 1% halothane in air and received intraperitoneal injections of taurine (0.25, 0.5 and 1 g/kg). Control animals received saline injections. Two hr later rats were sacrificed with an overdose of halothane and the striata and hippocampi dissected out. Tissue samples were weighed and homogenized in artificial cerebrospinal fluid containing (mM): 120 NaCl, 2.8 KCl, 25 NaHCO 3 , 1.2 CaCl 2 , and 1.0 MgCl 2 , at pH 7.2, adjusted by bubbling of the solution with 5% CO 2 . Aliquots of the homogenate were mixed with sulfosalicylic acid (final concentration 5%) and centrifuged. The supernatants were removed and stored at –20 o C until analyzed. Prior to amino acid detection the supernatant samples were diluted in 0.29 M borate buffer, pH 10.4. The concentrations of taurine, glutamate, GABA, glutamine and alanine were measured by HPLC with fluorescent detection after precolumn-derivatization with o-phtaldialdehyde and low-pressure gradient elution, as described in Molchanova et al. [21]. RESULTS In control rats, the taurine concentration in the hippocampus was significantly lower than that of glutamate, while the striatum contained equal amounts of both (Table 1). The injections of 0.25, 0.5 and 1 g/kg taurine increased the taurine Table I. Concentrations of taurine, glutamate, GABA, glutamine and alanine in the striatum and hippocampus of control rats. Amino acid Striatum mmol/kg wet weight Hippocampus mmol/kg wet weight Taurine 8.96±0.41 6.66±0.26 Glutamate 8.72±0.49 9.44±0.79 GABA 2.56±0.19 1.88±0.11 Glutamine 3.01±0.18 2.29±0.24 Alanine 2.76±0.41 2.52±0.52 Data are given as mean values ± S.E.M from twelve experiments. 95