Suppressive effect of Saiko-ka-ryukotsu-borei-to, a herbal medicine, on excessive release of glutamate in the hippocampus.
Glutamate is the major excitatory neurotransmitter in the brain, and the excess of glutamate concentration in the synaptic cleft is a cause of neuronal injury or death. To find out a drug suppressing the excess of extracellular glutamate concentration, the effect of Saiko-ka-ryukotsu-borei-to, a herbal medicine, was examined in the control and zinc-deficient rats, a neurological disease model, by using in vivo microdialysis. The excessive increase in extracellular glutamate in the hippocampus was induced by perfusion with 100 mM KCl for 40 min. Administration of Saiko-ka-ryukotsu-borei-to did not appreciably influence the increase in body weight of the control rats and the retarded increase in body weight of zinc-deficient rats. However, administration of Saiko-ka-ryukotsu-borei-to to the control rats completely suppressed the increase in glutamate concentration in the hippocampal extracellular fluid during stimulation with high K+. The suppressive effect of Saiko-ka-ryukotsu-borei-to was also observed in zinc-deficient rats, in which extracellular glutamate concentration was markedly increased during stimulation with high K+. These results suggest that Saiko-ka-ryukotsu-borei-to is a useful drug for prevention or cure of excitotoxicity of glutamate.
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
Haruna
H
Tamano
Atsushi
A
Takeda
D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D005526:Food, Formulated; D018698:Glutamic Acid / Q000378:metabolism* / Q000633:toxicity; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D017551:Microdialysis; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015032:Zinc / Q000172:deficiency*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D004365:Drugs, Chinese Herbal; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; C095444:saiko-ka-ryukotsu-borei-to; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D011189:Potassium Chloride; D015032:Zinc