Böhm M, Gierschik P, Erdmann E
Medizinische Klinik I der Universität München, FRG.
Basic Res Cardiol. 1992;87 Suppl 1:37-50. doi: 10.1007/978-3-642-72474-9_3.
Heterotrimeric Gi-proteins play an important role in the regulation of cardiac adenylate cyclase. Besides a downregulation of beta-adrenoceptors with an accompanying reduction of the positive inotropic effects of cAMP-dependent positive inotropic agents, an increase of pertussis toxin substrates (Gi alpha-proteins) has been observed. The increase of Gi alpha has been reported to be associated with a reduced adenylate cyclase activity in dilated cardiomyopathy from hearts with heart failure class NYHA IV. Since the quantification of Gi alpha-proteins with the pertussis toxin labeling method is hampered by a number of biological and technical factors, Gi alpha-proteins were quantified radioimmunologically using the iodinated C-terminus 125I-KENLKDCGLF as tracer, purified retinal transducin alpha as standard, and an antiserum (DS 4) raised against the same peptide. With this technique Gi alpha-proteins were increased by 118% in dilated cardiomyopathy and 48% in ischemic cardiomyopathy, although pertussis toxin substrates were only increased by 40% in dilated cardiomyopathy and no change was observed in ischemic cardiomyopathy. In cardiomyopathic tissue, an inverse relationship was observed between the increase of Gi alpha and the positive inotropic effects of isoprenaline or milrinone. These data provide evidence for a functional role of Gi alpha in the reduced positive inotropic effects of cAMP-dependent positive inotropic agents. In addition, results obtained with pertussis toxin labeling for quantification of Gi alpha-proteins do not necessarily reflect the expression of Gi alpha-proteins in the human myocardium.
异三聚体Gi蛋白在心脏腺苷酸环化酶的调节中起重要作用。除了β-肾上腺素能受体下调并伴随cAMP依赖性正性肌力药物的正性肌力作用减弱外，还观察到百日咳毒素底物（Giα蛋白）增加。据报道，在纽约心脏协会（NYHA）心功能IV级心力衰竭患者的扩张型心肌病中，Giα增加与腺苷酸环化酶活性降低有关。由于用百日咳毒素标记法对Giα蛋白进行定量受到许多生物学和技术因素的阻碍，因此采用碘化C末端125I-KENLKDCGLF作为示踪剂、纯化的视网膜转导蛋白α作为标准品以及针对同一肽段产生的抗血清（DS 4），通过放射免疫法对Giα蛋白进行定量。用这种技术，在扩张型心肌病中Giα蛋白增加了118%，在缺血性心肌病中增加了48%，尽管在扩张型心肌病中百日咳毒素底物仅增加了40%，而在缺血性心肌病中未观察到变化。在心肌病组织中，观察到Giα增加与异丙肾上腺素或米力农的正性肌力作用呈负相关。这些数据为Giα在cAMP依赖性正性肌力药物正性肌力作用减弱中的功能作用提供了证据。此外，用百日咳毒素标记法对Giα蛋白进行定量所得到的结果不一定反映人心肌中Giα蛋白 的表达情况。
