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Mechanisms of non-adrenergic sympathetic regulation of peripheral metabolism.

外周代谢的非肾上腺素交感神经调节机制。

基本信息

批准号：
62480128
负责人：
SHIMAZU Takashi
金额：
$ 4.35万
依托单位：
Ehime University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1989
项目状态：
已结题

项目摘要

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 … More 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

虽然交感神经的代谢调节被认为是由交感神经递质去甲肾上腺素介导的，但最近的证据表明，非肾上腺素能传递也参与了这种代谢调节。例如，使用原位灌注的肝神经-肝脏制备物，电刺激节后交感神经纤维导致磷酸化酶α活性和肝脏葡萄糖输出的快速增加，并且交感神经刺激对肝糖原分解的这种作用只能通过α-肾上腺素能阻断剂酚苄明和β-拮抗剂普萘洛尔的存在而部分防止。为了分离一种可能介导非肾上腺素能交感神经激活肝磷酸化酶的因子，我们从腹腔神经节中纯化了该因子，并将其鉴定为腺苷。此外，研究发现，三尖杉酯碱还参与了hep的神经激活过程 ...更多信息本研究项目的第二个方法是建立交感神经对棕色脂肪组织（BAT）脂肪生成的非肾上腺素能介导作用机制。结果表明，电刺激，在突发，进入肩胛间BAT的交感神经引起脂肪酸合成率的显着增加。然而，这种作用的交感神经刺激的爆发不能防止在所有的α和β肾上腺素能阻滞。输注去甲肾上腺素也不能模拟交感神经对脂肪酸合成的影响。此外，间歇性电刺激的瓷砖交感神经不能增加甘油合成的速率，但它诱导的脂肪酸合成率的矛盾增加后，结合α-和β-肾上腺素能阻滞。这些结果表明去甲肾上腺素似乎不介导交感神经的脂肪生成作用。在寻找确定一个负责BAT脂肪生成的非肾上腺素能交感神经激活的因素，我们开发了一个测定系统与棕色脂肪细胞的悬浮液，并测试了各种神经肽和其他物质在刺激脂肪酸合成的活性，这些物质都是有效的脂肪酸合成。然而，从大鼠下丘脑部分纯化的提取物被发现含有刺激棕色脂肪细胞的脂肪酸合成的神经因子。少