Feldman A M, Cates A E, Veazey W B, Hershberger R E, Bristow M R, Baughman K L, Baumgartner W A, Van Dop C
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
J Clin Invest. 1988 Jul;82(1):189-97. doi: 10.1172/JCI113569.
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.
人类心力衰竭与对β-肾上腺素能激动剂的收缩反应减弱有关。我们推测鸟嘌呤核苷酸结合调节蛋白（G蛋白）活性的改变可能部分导致了这种异常。因此，我们利用细菌毒素催化的ADP核糖基化来测量衰竭人类心肌中G蛋白的活性。与非衰竭对照组相比，衰竭人类心脏中40,000摩尔质量百日咳毒素底物（αG40）的活性增加了36%。相比之下，刺激性调节亚基（Gs）的水平没有变化。αG40活性的增加与基础以及5'-鸟苷酰亚胺二磷酸刺激的腺苷酸环化酶活性降低30%有关。这些数据表明，αG40活性增加是衰竭心肌的一个新标志，并且可能至少部分解释了衰竭人类心脏对β1-肾上腺素能激动剂反应性降低的原因。
