Mechanisms of non-adrenergic sympathetic regulation of peripheral metabolism.

虽然交感神经对代谢的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，使用原位灌流的肝神经-肝制剂，电刺激节后交感神经纤维可导致肝脏磷酸化酶a活性和葡萄糖产量的迅速增加，而交感神经刺激对肝糖原分解的这种影响仅可被α-肾上腺素能阻滞剂苯氧苯甲胺和β-受体拮抗剂普萘布洛尔部分阻止。为了分离一个可能介导肝脏磷酸化酶非肾上腺素交感激活的因子，我们从腹腔神经节中纯化了这个因子，并将其鉴定为腺苷。此外，还发现前列腺素也参与了hep…的神经激活。本研究项目的第二个途径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中介作用的机制。结果表明，突发性电刺激进入肩周肌的交感神经可显著增加脂肪酸合成速率。然而，突发性交感神经刺激的这种效应根本不能被α和β肾上腺素能阻断所阻止。注射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，间歇性电刺激交感神经不能增加甘油三酯合成率，但在α-和β-肾上腺素能阻滞剂联合阻断后，却引起脂肪酸合成率的反常增加。这些结果表明，去甲肾上腺素似乎不能介导交感神经的生脂作用。为了确定蝙蝠脂肪生成的非肾上腺素交感激活的因素，我们开发了一个棕色脂肪细胞悬浮液的测定系统，并测试了各种神经肽和其他物质刺激脂肪酸合成的活性；这些物质都不能有效地促进脂肪酸合成。然而，从大鼠下丘脑提取的部分纯化的提取物被发现含有一种神经因子，可以刺激棕色脂肪细胞的脂肪酸合成。较少

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