Evaluation of the Protective Effects of Cyclosporin A and FK506 on Abnormal Cytosolic and Mitochondrial Ca<SUP>2+</SUP> Dynamics During Ischemia and Exposure to High Glutamate Concentration in Mouse Brain Slice Preparations
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概要
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We examined the protective effects of the immunosuppressants cyclosporin A (CsA) and FK506 on abnormal cytosolic Ca<SUP>2+</SUP> ([Ca<SUP>2+</SUP>]c) and mitochondrial Ca<SUP>2+</SUP> concentration ([Ca<SUP>2+</SUP>]m) dynamics induced by ischemia or high L-glutamate concentration in mouse brain slice preparations. We used fura-4F and rhod-2 as indicators for [Ca<SUP>2+</SUP>]c and [Ca<SUP>2+</SUP>]m, respectively, in their acetoxymethylester form. Slice preparations loaded with either of these two indicators were exposed to ischemic artificial cerebrospinal fluid (oxygen- and glucose-deprived medium) for 12 min or to aerobic medium with high L-glutamate concentration (isotonic 20 mM L-glutamate) for 5 min. CsA (1 – 10 <I>μ</I>M) showed significant protective effects on the maximum increase in ischemia-induced [Ca<SUP>2+</SUP>]c and [Ca<SUP>2+</SUP>]m. FK506 (10 <I>μ</I>M) showed significant protective effects on the [Ca<SUP>2+</SUP>]m increase, but not on the ischemia-induced [Ca<SUP>2+</SUP>]c increase. Both immunosuppressants showed almost equal protective effects on the [Ca<SUP>2+</SUP>]c and [Ca<SUP>2+</SUP>]m increases induced by high L-glutamate concentration. These results suggest that the protective effects of CsA and FK506 on Ca<SUP>2+</SUP> overloading may be dependent upon the common pharmacological sites of actions relating to their effects as immunosuppressants. The small, but significant depressant effects of these drugs could give us important clues for rescuing critical brain damage induced by Ca<SUP>2+</SUP> overloading.
著者
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Omi Akibumi
Department Of Anesthesia Kosei Chuo General Hospital
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Uchino Hiroyuki
Department Of Anesthesiology Hachioji Medical Center Tokyo Medical University
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Kudo Yoshihisa
School Of Life Science Tokyo University Of Pharmacy And Life Science
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Ikeda Yukio
Department Of Earth Science Faculty Of Science Ibaraki University
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Kudo Yoshihisa
School of Life Science, Tokyo University of Pharmacy and Life Sciences, Japan
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Yokoyama Tomoharu
Department of Emergency and Critical Care Medicine and Neurosurgery, Tokyo Medical University Hachioji Medical Center, Japan
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Tanoue Tadashi
Department of Anesthesiology, Kumamoto Regional Medical Center, Japan
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Hasegawa Erika
School of Life Science, Tokyo University of Pharmacy and Life Sciences, Japan
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Ohta Shouichi
Department of Emergency and Critical Care Medicine and Neurosurgery, Tokyo Medical University Hachioji Medical Center, Japan
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Uchino Hiroyuki
Department of Anesthesiology, Tokyo Medical University, Japan
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Omi Akibumi
Department of Anesthesiology, Tokyo Medical University, Japan
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