INCREASE OF THE 40,000-MOL WT PERTUSSIS TOXIN SUBSTRATE (G-PROTEIN) IN THE FAILING HUMAN-HEART
INCREASE OF THE 40,000-MOL WT PERTUSSIS TOXIN SUBSTRATE (G-PROTEIN) IN THE FAILING HUMAN-HEART
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DOI：
10.1172/jci113569
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发表时间：
1988-07-01
影响因子：
15.9
通讯作者：
VANDOP, C
中科院分区：
文献类型：
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作者：
FELDMAN, AM;CATES, AE;VANDOP, C
人心力衰竭与对β-受体拮抗剂的收缩反应减弱有关。肾上腺素能激动剂我们推测鸟嘌呤核苷酸结合调节蛋白（G蛋白）活性的改变可能是导致这种异常的部分原因。因此，我们利用细菌毒素催化的ADP核糖基化来测量G蛋白在衰竭的人类心肌中的活性。当与非衰竭对照相比时，40，000-mol wt百日咳毒素底物（α G40）的活性在衰竭的人心脏中增加了36%。相反，刺激调节亚基（Gs）的水平没有变化。α G40中活性的增加与基础以及5“-鸟苷酰亚氨基二磷酸刺激的腺苷酸环化酶活性的30%降低有关。这些数据表明，α G40活性的增加是衰竭心肌的新标记，并且可以至少部分地解释衰竭人心脏中对β 1-肾上腺素能激动剂的反应性降低。
Human heart failure is associated with a diminished contractile response to .beta.-adrenergic agonists. We hypothesized that alterations in the activity of a guanine nucleotide-binding regulatory protein (G protein) might be partially responsible for this abnormality. We therefore measured the activity of G proteins in failing human myocardium utilizing bacterial toxin-catalyzed ADP ribosylation. The activity of a 40,000-mol wt pertussis toxin substrate (.alpha.G40) was increased by 36% in failing human hearts when compared with nonfailing controls. In contrast, there was no change in the level of the stimulatory regulatory subunit (Gs). The increased activity in .alpha.G40 was associated with a 30% decrease in basal as well as 5''-guanylyl imidodiphosphate-stimulated adenylate cyclase activity. These data suggest that increased .alpha.G40 activity is a new marker for failing myocardium and may account at least in part for the diminished responsiveness to .beta.1-adrenergic agonists in the failing human heart.