[Effects of excitatory sulfur amino acids on glutamate transport in synaptosomes isolated from the rat cerebral cortex].
Transport of glutamate, the disturbance of which has been implicated in amyotrophic lateral sclerosis (ALS), may be influenced by various substances. Excitatory sulfur amino acids (SAAs) could be increased in ALS, because the elevation of taurine, the final product of the metabolic pathway of SAAs, has been reported in this intractable disease. I examined effects of excitatory SAAs on the transport of glutamate in synaptosomes. Synaptosome fractions were prepared by discontinuous density-gradient centrifugation from the rat cerebral cortex, and were incubated at 35 degrees C with varying concentrations of L-[3H] glutamate in the absence or presence of excitatory SAAs; cysteine sulfinic acid (CSA), cysteic acid (CA), homocysteine sulfinic acid (HCSA), homocysteic acid (HCA) and S-sulfocysteine (SC). Kinetic characterization of uptake confirmed the high-affinity nature of the transport system, the Michaelis constant (Km) for glutamate uptake being 10 microM. The nature of inhibition was competitive. Potent inhibition of transport was exhibited by CSA and CA, whereas substantially weaker inhibitory effects were exhibited by HCSA, and almost no effects by HCA or SC. Inhibition by excitatory SAAs, especially CSA and CA of the high-affinity glutamate transporter may be involved in the pathogenesis of ALS.
Kuroda
K
K
First Department of Internal Medicine, Kyorin University School of Medicine.
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D027322:Amino Acid Transport System X-AG; D000690:Amyotrophic Lateral Sclerosis / Q000209:etiology; D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D018846:Excitatory Amino Acids / Q000378:metabolism / Q000494:pharmacology*; D005971:Glutamates / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000378:metabolism*; D013654:Taurine / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D018846:Excitatory Amino Acids; D005971:Glutamates; D013654:Taurine