| Project/Area Number |
05454145
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
ABIKO Yasushi Asahikawa Medical College, School of Medicine, Professor, 医学部・薬理学講座, 教授 (90041821)
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| Co-Investigator(Kenkyū-buntansha) |
HARA Akiyoshi Asahikawa Medical College, School of Medicine, Assistant, 医学部・薬理学講座, 助手 (90164988)
YAZAWA Kazuto Asahikawa Medical College, School of Medicine, Assistant, 医学部・薬理学講座, 助手 (90212274)
HASHIZUME Hiroko Asahikawa Medical College, School of Medicine, Associate Professor, 医学部・薬理学講座, 助教授 (00154021)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1993: ¥6,300,000 (Direct Cost: ¥6,300,000)
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| Keywords | OXYGEN RADICAL / HYDROGEN PEROXIDE / INTRACELLULAR CALCIUM / LYSOPHOPHATIDYLCHOLINE / d-PROPRANOLOL / DILAZEP / 虚血・再潅流障害 / ラット心室筋細胞 / [Ca^<2+>]_<in> / veratridine / Na^+チャネル / propranolol / 心筋 / リドカイン |
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| Research Abstract |
We found that H_2O_2 produces ischemia/reperfusion-like changes on the isolated rat heart in both mechanical and metabolic functions and lipid peroxidation, and that lidocain decreases the H_2O_2-induced damage. These results support our hypothesis that oxygen radicals produce ischemia/reperfusion damage, and that the anti-ischemic drug protects the myocardial damage induced by oxygen radicals. We also found that H_2O_2 produces cell damage in the presence of Fe^<2+> in the isolated cardiac cells. The H_2O_2-induced damage to the myocyte was protected by d-propranolol and K-7259, a novel derivative of dilazep. Next, we found that LPC produced ischemia/reperfusion-like damage to the isolated heart, and that d-propranolol and K-7259 attenuated the LPC-induced damage to the isolated haert. In the next experiments, we measured intraceullar Ca^<2+> concentration ([Ca^<2+>]_i) in the cardiac myocyte. LPC increased ([Ca^<2+>]_i) markedly and dilazep and d-propranolol attenuated the LPC-induced increase in ([Ca^<2+>]_i). Next, we examined the effect of beta-adrenoceptor antagonists on the LPC-induced increase in ([Ca^<2+>]_i), and found that l- and d-propranolol, and l- and dpenbutolol were effective in attenuating the LPC-induced increased in ([Ca^<2+>]_i). Lastly, we examined the effect of LPC on the ion channel in the cardiac myocyte, and found that LPC increases the non-selective cation channel current through which Ca^<2+> can pass.
These results suggst that oxygen radicals like hydrogen peroxide produces peroxidation of the phospholipids of the cardiac cell membrane, releasing LPC.LPC then increases ([Ca^<2+>]_i) through non-selective cation channel. d-Propranolol and K-7259, a derivative of dilazep, attenuated both H_2O_2-induced and LPC-induced damage to the cardiac myocyte.
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