| Project/Area Number |
62570713
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
麻酔学
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| Research Institution | University of Occupational and Environmental Health, School of Medicine. |
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Principal Investigator |
SHIGEMATSU Akio (1988) University of Occupational and Environmental Health, School of Medicine, Department of Anesthesiology, Professor., 医学部・麻酔科, 教授 (30037428)
高良 裕 (1987) 産業医科大学, 麻酔科学教室, 講師 (30148952)
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| Co-Investigator(Kenkyū-buntansha) |
WADA Akihiko University of Occupational and Environmental Health, School of Medicine, Departm, 医学部・薬理学, 助教授 (30131949)
TAKARA Hiroshi University of Occupational and Environmental Health, School of Medicine, Departm (30148952)
重松 昭生 産業医科大学, 麻酔科学教室, 教授 (30037428)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1988: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1987: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Anesthetics / Ion channel / Sodium / Calcium / Binding site / Catecholamine secretion / Anesthetics / Anesthetics. / 副腎髄質 / アセチルコリン受容体 / イオンチャンネル / カテコールアミン分泌 / 麻酔薬 |
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| Research Abstract |
The effects of general anesthetics on several distinct types of ion channels were investigated in cultured bovine adrenal medullary cells. In these cells, our previous studies suggest that carbachol-induced Na influx via nicotinic receptor-ion channel complex or veratridine-induced na influx via voltage-dependent Na channel causes ca influx via voltage-dependeut Ca channel and triggers catecholamine secretion, whereas high concentration of extracellular potassium directly activates voltage-dependent Ca channel without increasing Na influx.
1. Phencyclidine inhibited influx of ^<22>Na, ^<45>Ca and secretion of catecholamines caused by carbachol (IC_<50> 7.0 muM) or by veratridine (IC_<50> 60.0 muM). Clinical concentrations of ketamine suppressed carbachol-induced events (IC_<50> 40.0 muM) with less inhibiting veratridine-induced events (IC_<50> 260 muM). droperidol suppressed veratridine-induced events (IC_<50> 34 muM), but less affected carbachol-induced events (IC_<50> >100 muM).
2. Phencyclidine, ketamine and droperidol did not alter high concentration of extracellular potassium-induced ^<45>Ca influx and catecholamine secretion.
3. Scatchard analysis of [^3H]-phencyclidine specific binding revealed two different equilibrium dissociation constants (4.3 and 77.4 muM). [^3H]-Phencyclidine binding was not inhibited by carbachol, muscarine, d-tubocurarine, hexamethonium, tetrodotoxin, veratridine and -scorpion venom. Droperidol (100 muM) and ketamine (100 muM) reduced [^3H]-phencyclidine binding to 40.3 and 80.1% of control.
4.These results indicate that general anesthetics used bind to two distinct classes of sites, each of which is functionally associated with nicotinic receptor-ion channel complex and with voltage-dependent Na channel and inhibit Na influx. Anesthetics do not interfere with voltage-dependent Ca channel, but inhibition of Na influx leads to the reduction of Ca influx and catecholamine secretion caused by carbachol and by veratridine.
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