Age-related changes in the control of hepatic cyclic AMP levels by alpha 1- and beta 2-adrenergic receptors in male rats.
Age-related changes in the control of hepatic cyclic AMP levels by alpha 1- and beta 2-adrenergic receptors in male rats.
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DOI：
10.1016/s0021-9258(18)32544-4
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发表时间：
1983-04
期刊：
影响因子：
--
通讯作者：
N. Morgan;P. Blackmore;J. Exton
中科院分区：
文献类型：
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作者：
N. Morgan;P. Blackmore;J. Exton
幼年雄性大鼠肝细胞(80-110g)对肾上腺素的反应使cAMP升高12倍，这是由β2-肾上腺素能受体介导的。在这些细胞中，α1或β2肾上腺素能单独刺激都能激活磷酸化酶和葡萄糖的释放，尽管α1磷酸化酶对肾上腺素的反应是肾上腺素的10倍，并导致该酶的激活更快(约S 10-20倍)。这表明，β2-肾上腺素能反应对于糖原分解在功能上并不重要，即使在幼年大鼠中也是如此。然而，β2-肾上腺素能刺激确实增加了这些细胞中[U-14C]乳酸的糖异生速率。雄性大鼠的衰老与β2肾上腺素能cAMP反应的减弱以及α1受体介导的cAMP积聚的出现有关。α1-肾上腺素能/cAMP系统对肾上腺素能激动剂和拮抗剂的作用顺序与α1-肾上腺素能/钙离子系统相同。这些数据表明，在成熟时，肝脏α1受体与两种不同的转导机制有关，即钙动员和cAMP生成。成年雄性大鼠肝细胞缺钙，但幼年雄性大鼠肝细胞对肾上腺素的cAMP反应的α1组分增加，但在这种情况下，磷酸化酶的α1激活发生得比钙充足的细胞慢。阻断α2-肾上腺素能受体并不能显著改变儿茶酚胺对任何年龄雄性大鼠肝细胞cAMP或磷酸化酶a水平的影响，这表明这些受体在调节糖原分解方面缺乏功能意义。
Hepatocytes from juvenile male rats (80-110 g) showed a 12-fold elevation of cAMP in response to epinephrine, which was mediated by beta 2-adrenergic receptors. In these cells, either alpha 1- or beta 2-adrenergic stimulation alone activated phosphorylase and glucose release although the alpha 1-phosphorylase response was 10-fold more sensitive to epinephrine and resulted in more rapid (by 10-20 s) activation of the enzyme. This suggests that the beta 2-adrenergic response is functionally unimportant for glycogenolysis, even in juvenile rats. beta 2-Adrenergic stimulation did, however, produce an increase in the rate of gluconeogenesis from [U-14C] lactate in these cells. Aging in the male rat was associated with attenuation of the beta 2-adrenergic cAMP response coupled with the emergence of an alpha 1-receptor-mediated accumulation of cAMP. The order of potency displayed by the alpha 1-adrenergic/cAMP system to adrenergic agonists and antagonists was identical with that of the alpha 1-adrenergic/Ca2+ system. These data suggest that, in maturity, hepatic alpha 1-receptors become linked to 2 separate transduction mechanisms, namely Ca2+ mobilization and cAMP generation. Calcium depletion of hepatocytes from adult, but not juvenile, male rats increased the alpha 1-component of the cAMP response to epinephrine, but under these conditions, alpha 1-activation of phosphorylase occurred more slowly than in calcium-replete cells. Blockade of alpha 2-adrenergic receptors did not significantly modify catecholamine effects on hepatocyte cAMP or phosphorylase a levels in male rats at any age studied, suggesting a lack of functional significance for these receptors in the regulation of glycogenolysis.