ACTIVATION OF 2 SIGNAL-TRANSDUCTION SYSTEMS IN HEPATOCYTES BY GLUCAGON
ACTIVATION OF 2 SIGNAL-TRANSDUCTION SYSTEMS IN HEPATOCYTES BY GLUCAGON
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DOI：
10.1038/323068a0
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发表时间：
1986-09-04
期刊：
影响因子：
64.8
通讯作者：
HOUSLAY, MD
中科院分区：
文献类型：
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作者：
WAKELAM, MJO;MURPHY, GJ;HOUSLAY, MD
胰高血糖素刺激肝脏糖原分解的能力在环AMP和激素刺激的腺苷酸环化酶的经典鉴定中发挥了关键作用。但一些观察表明，胰高血糖素可以发挥作用独立于提高细胞内cAMP浓度[2 - 7]。这些影响可能是由细胞内游离Ca2+浓度的升高介导的，尽管其发生的机制尚不清楚。我们在这里表明，在生理上发现的低浓度胰高血糖素，会导致肌醇磷脂的分解和肌醇磷酸的产生。事实上，我们发现胰高血糖素类似物（1-N-α-三硝基苯基组氨酸，12-同型精氨酸）胰高血糖素（th -胰高血糖素）不会激活腺苷酸环化酶或引起肝细胞中cAMP的任何增加，但可以充分刺激糖原分解、糖异生和尿素合成10，刺激肌醇磷酸的产生。低浓度胰高血糖素对肌醇磷脂代谢的刺激提供了一种机制11,12，胰高血糖素可以在靶细胞上发挥与camp无关的作用。我们认为肝细胞具有两种不同的胰高血糖素受体，一种GR-1受体偶联刺激肌醇磷脂分解，另一种GR-2受体偶联刺激腺苷酸环化酶活性。
The ability of glucagon to stimulate glycogen breakdown in liver played a key part in the classic identification of cyclic AMP and hormonally stimulated adenylate cyclase1. But several observations indicate that glucagon can exert effects independent of elevating intracellular cAMP concentrations2–7. These effects are probably mediated by an elevation8,9of the intracellular concentration of free Ca2+although the mechanism by which this occurs is unknown. We show here that glucagon, at the low concentrations found physiologically, causes both a breakdown of inositol phospholipids and the production of inositol phosphates. Indeed, we show that the glucagon analogue, (1-N-α-trinitrophenylhistidine,12-homo-arginine)glucagon (TH-glucagon), which does not activate adenylate cyclase or cause any increase in cAMP in hepatocytes yet can fully stimulate glycogenolysis, gluconeogenesis and urea synthesis10, stimulates the production of inositol phosphates. This stimulation of inositol phospholipid metabolism by low concentrations of glucagon provides a mechanism11,12whereby glucagon can exert cAMP-independent actions on target cells. We suggest that hepatocytes possess two distinct receptors for glucagon, a GR-1 receptor coupled to stimulate inositol phospholipid breakdown and a GR-2 receptor coupled to stimulate adenylate cyclase activity.