Involvement of Enhanced Glutamate Release in Halogenated volatile Anesthetic-induced Central Nervous System Excitation

Research Project

Project/Area Number	06671556
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Anesthesiology/Resuscitation studies
Research Institution	Kansai Medical University
Principal Investigator	HIROSE Takuji Kansai Medical University, The Department of Medicine, Assistant, 医学部, 助手 (30189881)
Project Period (FY)	1994 – 1995
Project Status	Completed (Fiscal Year 1995)
Budget Amount *help	¥2,100,000 (Direct Cost: ¥2,100,000) Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000) Fiscal Year 1994: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywords	Halogenated Anesthetics / Volatile Anesthetics / Halogenated Ethane / Convulsion / CNS Excitation / Glutamate / Excitatory Amino Acid / Microdialysis / ハロゲン化揮発性麻酔薬 / マイクロダイアリシス法 / ハロゲン化揮発性吸入麻酔薬
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.