ELIMINATION OF GTP BIPHASIC REGULATION OF SYNAPTOSOMAL ADENYLATE CYCLASE BY MANGANESE AND SOLUBILIZATION
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概要
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Effects of divalent cations and solubilization with Lubrol-PX were studied on guanine nucleotide regulation of synaptosomal adenylate cyclase activity of the rat caudate nucleus. In the presence of Mg<SUP>2+</SUP>, both GTP and Gpp(NH)p exerted biphasic actions on the membrane-bound adenylate cyclase activity. The K<SUB>0.5</SUB> value for the GTP stimulation of the cyclase was 47 nM, and the value for the GTP inhibition was 4.5 μM. One hundred μM dopamine selectively enhanced the stimulatory phase of the GTP action, whereas 10μM morphine selectively enhanced the inhibitory phase of the GTP action. When Mg<SUP>2+</SUP> was replaced by Mn<SUP>2+</SUP>, the inhibition of the membrane-bound adenylate cyclase by these nucleotides and morphine was completely abolished; but the catalytic activity of adenylate cyclase was not impaired. These results suggest that the inhibitory action of GTP is responsible for the morphine inhibition of synaptosomal adenylate cyclase. Lubrol-solubilized adenylate cyclase prefered Mn<SUP>2+</SUP> to Mg<SUP>2+</SUP> for its activity. The stimulation of adenylate cyciase by either GTP or Gpp (NH)p was eliminated in the Sepharose 6B-fractionated solubilized preparation in the presence of either Mg<SUP>2+</SUP> or Mn<SUP>2+</SUP>. Ten mM NaF also failed to activate the fractionated adenylate cyclase. In the fractionated solubilized preparation, GTP and Gpp(NH)p failed to inhibit adenylate cyclase. These results indicate that GTP and Gpp(NH)p are unable to inhibit the resolved catalytic unit of the synaptosomal adenylate cyclase.
- 社団法人 日本薬理学会の論文
著者
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Miura Kiyoshi
Department Of Physics Kyushu University:atsugi Plant Sony Corp.
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Fujimura Hajime
Department Of Pharmacology Gifu University School Of Medicine
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KAMIKUBO Keita
Department of Internal Medicine and Pharmacology, Gifu University School of Medicine
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Miura Kiyoshi
Department Of Geology Faculty Of Education Shimane University
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MIURA Kiyoshi
Department of Internal Medicine and Pharmacology, Gifu University School of Medicine
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FUJIMURA Hajime
Department of Internal Medicine and Pharmacology, Gifu University School of Medicine
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