1995 Fiscal Year Final Research Report Summary
Involvement of Enhanced Glutamate Release in Halogenated volatile Anesthetic-induced Central Nervous System Excitation
Project/Area Number |
06671556
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
Anesthesiology/Resuscitation studies
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Research Institution | Kansai Medical University |
Principal Investigator |
HIROSE Takuji Kansai Medical University, The Department of Medicine, Assistant, 医学部, 助手 (30189881)
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Project Period (FY) |
1994 – 1995
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Keywords | Halogenated Anesthetics / Volatile Anesthetics / Halogenated Ethane / Convulsion / CNS Excitation / Glutamate / Excitatory Amino Acid / Microdialysis |
Research Abstract |
(1)The present experiments aimed to elucidate the mechanisms of excitatory effects of volatile anesthetics and convulsant. In ddN mice, enflurane (2% in air), sevoflurane (2%) or isoflurane (1.2%) induced opisthotonus. In ddY mice, a halogenated ethane, tetrachlorodifluoroethane (CC12FCC12F : DF-112, 2%) induced tonic-clonic convulsion. These CNS excitatory effects were suppressed by pretreatment with an N-methyl-D-aspartate antagonist, MK-801 (0.5mg/kg). Halogenated volatile anesthetics (enflurane, sevoflurane, isoflurane and halothane) increased glutamate release from synaptosomes of the mouse cerebral cortex at concentrations corresponding to those used clinically. By contrast, diethyl ether which has no halogen atoms did not affect glutamate release over a wide range of concentrations. The convulsive gas, DF-112, released glutamate more potently than anesthetics. (2)We have applied brain microdialysis-HPLC procedure to estimate amino acids release in rat hippocampus during the inhalation of halogenated volatile agents. Volatile anesthetics did not affect amino acids levels in dialysates, while volatile convulsant, DF-112 slightly but not significantly increased glutamate level in the dialysate. (3)These data suggest the involment of enhanced glutamate release in the mechanisms of excitatory effects of halogenated volatile anesthetics and convulsants. The CNS excitations must occur when excitatory stimuli resulting from excessive release of excitatory amino acid may overcome postsynaptic inhibition.
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Research Products
(2 results)