1988 Fiscal Year Final Research Report Summary
Action of anesthetics on acetylcholine receptor and voltage-dependent Na channel in cultured adrenal medullary cells.
| 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 University of Occupational and Environmental Health, School of Medicine, Department of Anesthesiology, Professor., 医学部・麻酔科, 教授 (30037428)
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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)
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| Project Period (FY) |
1987 – 1988
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| Keywords | Anesthetics / Ion channel / Sodium / Calcium / Binding site / Catecholamine secretion / Anesthetics |
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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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