| Project/Area Number |
62480128
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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 medical chemistry
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| Research Institution | Ehime University |
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Principal Investigator |
SHIMAZU Takashi Ehime University, School of Medicine, Professor, 医学部 (30090400)
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| Co-Investigator(Kenkyū-buntansha) |
MINOKOSHI Yasuhiko Ehime University, School of Medicine, Assistant Professor, 医学部, 助手 (10200099)
TAKAHASHI Akira Ehime University, School of Medicine, Assistant Professor, 医学部, 助手 (40171467)
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| Project Period (FY) |
1987 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1989: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1988: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1987: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | Sympathetic nerve / Non-adrenergic sympathetic regulation / Liver phosphorylase / alpha-and beta-Adrenergic blockers / Brown adipocytes / Fatty acid synthesis / 神経ペプチド / α,βブロッカー / グアネチジン / 代謝調節 / 肝ホスホリラーゼ |
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| Research Abstract |
Although sympathetic neural regulation of metabolism is considered to be mediated by the sympathetic neurotransmitter noradrenaline, recent evidence has suggested that a non-adrenergic transmission is also involved in this metabolic regulation. With the use of hepatic nerve-liver preparation perfused in situ, for instance, electrical stimulation of the post-ganglionic sympathetic nerve fibers results in rapid increases in phosphorylase a activity and glucose output from the liver, and this effect of sympathetic nerve stimulation on hepatic glycogenolysis can be only partially prevented by the presence of both the alpha-adrenergic blocking agent phenoxybenzamine and tile beta-antagonist propranblol. In an attempt to isolate a factor that may mediate the non-adrenergic sympathetic activation of liver phosphorylase, we purified this factor from the celiac ganglia and identified it as adenosine. In addition, it was found that prostaglandins are also involved in the neural activation of hep
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atic glycogenolysis.
The second approach of this research project is to establish the mechanism of nonadrenergic mediation of sympathetic nerve effect on brown adipose tissue (BAT) lipogenesis. It was shown that electrical stimulation, in bursts, of the sympathetic nerves entering the interscapular BAT caused a marked increase in the rate of fatty acid synthesis. However, this effect of sympathetic nerve stimulation in bursts could not be prevented at all by alpha- and beta- adrenergic blockade. Infusion of noradrenaline could also not mimic the sympathetic nerve effect on fatty acid synthesis. Moreover, intermittent electrical stimulation of tile sympathetic nerves could not increase the rate of glyceride glycerol synthesis, but it induced a paradoxical increase in the rate of fatty acid; synthesis after combined alpha-and beta-adrenergic blockade. These results indicate that noradrenaline seem not to mediate the lipogenic action of sympathetic nerve. In a search for identifying a factor responsible for the non-adrenergic sympathetic activation of BAT lipogenesis, we developed an assay system with a suspension of brown adipocytes and tested a variety of neuropeptides and other substances for their activity in stimulating fatty acid synthesis; none of these substances were effective for fatty acid synthesis. However, a partially purified extract from the rat hypothalamus was found to contain a neural factor that stimulates fatty acid synthesis of brown adipocytes. Less
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