[Glutamate transporter and neuronal cell death].
Glutamate transporters play an important role in keeping extracellular glutamate concentrations below the neurotoxic levels. We cloned a human glutamate transporter hGluT-1. In ischemic states, glutamate efflux via glutamate transporters and the extracellular glutamate concentrations are rapidly increased. These phenomenon enlarges the area of neuronal cell death. We showed that L-CCG-III, IV and glutamate block the reverse uptake (efflux) of glutamate in the hGluT-1 expressing HeLa cells. In amyotrophic lateral sclerosis, a glutamate transporter GLT1 was decreased. Decrease of the glutamate transporter will cause the elevation of extracellular glutamate concentrations and will lead to the neuronal injury. Bromocriptine enhances glutamate uptake 1.5 times than in its absence in the hGluT-1 expressing HeLa cells. Enhancing the removal of extracellular glutamate may produce similar effect as those achieved by glutamate-receptor antagonists. At two neuronal death conditions, we showed new possibilities of preventing neuronal cell death by the glutamate transporter regulators.
Kawakami
H
H
Third Department of Internal Medicine, Hiroshima University.
Yamashita
H
H
Nakayama
T
T
Nakamura
S
S
D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D027322:Amino Acid Transport System X-AG; D001692:Biological Transport; D016923:Cell Death; D006801:Humans; D009474:Neurons / Q000502:physiology*
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG