2001 Fiscal Year Final Research Report Summary
Effects of anesthetics on volume-sensitive chloride channels
| Project/Area Number |
12671476
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | The University of Tokushima |
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Principal Investigator |
TOMIYAMA Yoshinobu School of Medicine, The University of Tokushima, Assistant Professor, 医学部, 講師 (30243702)
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| Co-Investigator(Kenkyū-buntansha) |
KURODA Yasuhiro University Hospital, The University of Tokushima, Associate Professor, 医学部・附属病院, 助教授 (80234615)
OSHITA Syuzo School of Medicine, The University of Tokushima, Professor, 医学部, 教授 (60144945)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Volume-sensitive chloride channel / propofol / coronary artery smooth muscle cell / organ protection / organ toxicity / anesthetics |
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| Research Abstract |
Background: Inhibition of volume-sensitive chloride channels (VSCC) could produce both cardioprotection and cardiotoxicity. Propofol provides cardioprotection against ischemia-reperfusion injury, although cardiotoxicity is also reported. In this study, we investigated the effects of propofol on VSCC in cultured human coronary artery smooth muscle cells using fluorescence measurement. Methods: The chloride-sensitive dye, 6-methoxy-N-ethylquinolinium (MEQ), was loaded into cultured human coronary artery smooth muscle cells. To activate VSCC, hypotonic challenge was performed in the presence of gluconate- for 2 min. The percent reduction in MEQ fluorescence during a following period of 60 sec in the presence of SCN- was measured and used as an index of VSCC activity. Fivenitro-2- (3-phenylpropylamino) benzoic acid (NPPB), a well-characterized chloride channel blocker, and propofol were dissolved in hypotonic gluconate solution to test their effect on VSCC activity. Results: The reduction in fluorescence was inversely related to osmolality, indicating that activation of VSCC is osmolality-dependent. Hypotonic gluconate solution (210 mOsm/kg H2O) reduced fluorescence by 38.4 ± 2.6 %. The reduction in fluorescence due to hypotonic gluconate solution was dose-dependently inhibited by NPPB. Propofol at 0.3, 1, 3, 10, 30 and 100 ug/ml also significantly inhibited the reduction in fluorescence in hypotonic gluconate solution (210 mOsm/kg H2O) to 23.6 ±4.8 %, 19.7±7.4 %, 18.2±3.5 %, 17.6±5.0 %, 15.8±3.1 % and 10.3±3.9 %, respectively. Conclusions: Our results indicate that propofol inhibits VSCC in dose-dependent manner in cultured human coronary artery smooth muscle cells. This may explain in part both cardioprotective and cardiotoxic effects of propofol.
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