| Project/Area Number |
62570099
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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 |
General pharmacology
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| Research Institution | University of Occupational and Environmental Health, School of Medicine |
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Principal Investigator |
WADA Akihiko University of Occupational and Environmental Health, School of Medicine, Department of Pharmacology, Associate Professor, 医学部・薬理学, 助教授 (30131949)
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| Co-Investigator(Kenkyū-buntansha) |
TAKARA Hiroshi University of Occupational and Environmental Health, School of Medicine, Departm, 医学部・麻酔科学, 講師 (30148952)
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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 |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1988: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1987: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | Adrenal medulla / Ion channel / Catecholamine secretion / Sodium / Calcium / Potassium / Phencyclidine / 抗うつ薬 / 電位依存性Naチャンネル / ブレベトキシン / ベラトリジン / ネオスルガトキシン / ヒストリオニコトキシン / Na^+ / Ca^2+ / K^+ / μ-コノトキシン / カテコ-ルアミン分泌 |
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| Research Abstract |
1. [3H]Saxitoxin bound specifically to bovine adrenal medullary cells with equilibrium dissociation constant (Kd) of 5.8 nM and maximum binding capacity (Bmax) of 427.2 fmols/107 cells (124.2 fmols/ mg cell protein).
2. In bovine adrenal medullary cells, tricyclic (imipramine, amitriptyline and nortriptyline) and tetracyclic (maprotiline and mianserin) antidepressants inhibited influx of ^<22>Na, ^<45>Ca and secretion of catecholamines caused by carbachol (IC_<50> 14-96 muM) and by veratridine (IC_<50> 10-17 muM). Antidepressants did not suppress high K-induced 45Ca influx and catecholamine secretion. Specific binding of [^3H]imipramine had two different K_d values (13.3 and 165.0 muM). Tricyclic and tetracyclic antidepressants (but not cholinergic drugs and neurotoxins) competed for [^3H]imipramine binding. These results suggest that tricyclic and tetracyclic antidepressants bind to two populations of sites which are functionally associated with nicotinic receptor-associated ionic chan
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nels and with voltage-dependent Na channels, and inhibit Na influx. Inhibi on of Na influx leads to the reduction of Ca influx and catecholamine secretion due to carbachol and veratridine.
3. In bovine adrenal medullary cells, phencyclidine inhibited influx of ^<22>Na, ^<45>Ca, efflux of ^<86>Rb and secretion of catecholamines caused by carbachol (IC_<50> 7.0-10.0 muM) and by veratridine (IC_<50> 56.0-60.0 muM), but had to effect on high K-induced ^<45>Ca influx and catecholamine secretion. Scatchard analysis of [^3H]phencyclidine binding showed two different K_2 values (4.3 and 77.4 muM). [^3H]phencycliding binding was not inhibited by cholinergic drugs and neurotoxins. The results suggest that (1) phencyclidine does not inhibit voltage-dependent Ca channels and Ca-dependent K channels; (2) phencyclodine binds to two populations of sites, each of which is linked to nicotinic receptor-ion channel complex and to voltage-dependent Na channels, and inhibits Na influx. Inhibition of Na influx by phencyclodine leads to the redution of Ca influx, K efflux and catecholamine secretion caused by carbachol and by veratridine. Less
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