Neuropharmacological Characterization of Voltage-Sensitive Calcium Channels: Possible Existence of Neomycin-Sensitive, .OMEGA.-Conotoxin GVIA- and Dihydropyridines-Resistant Calcium Channels in the Rat Brain.
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概要
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We attemped to characterize the functional roles of subtypes of voltage-sensitive calcium channels in the brain. The maximal number of [<SUP>125</SUP>I]ω-conotoxin GVIA (ω-CTX) binding sites in rat brain associated with N-type calcium channels (N-channels) was approximately 10 times more than that of [<SUP>3</SUP>H]-PN200-110 associated with L-type calcium channels (L-channels). [<SUP>125</SUP>I]ω-CTX binding was inhibited by aminoglycoside antibiotics, neomycin and dynorphin A(1-13), but not by various classes of L-channel antagonists. A 6-hydroxydopamine-induced lesion of the striatum resulted in a marked reduction of both [<SUP>125</SUP>I]-ω-CTX and [<SUP>3</SUP>H]PN200-110 binding. Kainic acid-induced lesion of the striatum reduced [<SUP>3</SUP>H]PN200-110 binding by 57%, but did not reduce [<SUP>125</SUP>I]ω-CTX binding. ω-CTX produced a small (18%) but significant reduction of potassium-stimulated Ca<SUP>2+</SUP> influx into rat brain synaptosomes, although it produced a concentration-dependent inhibition in chick brain synaptosomes. Neomycin inhibited Ca<SUP>2+</SUP> influx in both preparations in a concentration-dependent manner. Both ω-CTX and neomycin inhibited potassium-stimulated [<SUP>3</SUP>H]dopamine (DA) release from rat striatal slices. The L-channel antagonists had no effect on either Ca<SUP>2+</SUP> influx or [<SUP>3</SUP>H]DA release. These results suggest that DA release in the striatum is regulated by Ca<SUP>2+</SUP> influx through N-channels located in presynaptic nerve terminals, and that the most of the Ca<SUP>2+</SUP> influx in rat brain appears to be governed by neomycin-sensitive, ω-CTX and DHP-resistant calcium channels.
- 公益社団法人 日本薬理学会の論文
著者
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Yamada Kiyofumi
Department Of Hospital Pharmacy Nagoya University School Of Medicine
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Nabeshima Toshitaka
Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences Meijo University
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Hasegawa Takaaki
Department Of Hospital Pharmacy Nagoya University School Of Medicine
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Morita Seiji
Third Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Co., Ltd.
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Teraoka Tomomi
Third Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Co., Ltd.
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HASEGAWA Takaaki
Department of Bacteriology, Nagoya University School of Medicine
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