Böhm M
Klinik III für Innere Medizin, Universität zu Köln, Germany.
Mol Cell Biochem. 1995;147(1-2):147-60.
Alterations of receptor-G-protein-regulated adenylyl cyclase activity have been suggested to represent an important alteration leading to contractile dysfunction in the failing human heart. Recent experiments suggest that the beta 1-adrenoceptor (beta 1 AR) density and mRNA levels are reduced, while beta 2-adrenoceptors and stimulatory G-proteins are unchanged (mRNA and protein level). Functional assays demonstrated that the catalyst of the adenylyl cyclase is not different between failing and nonfailing myocardium. Inhibitory G-proteins are increased (pertussis toxin substrates, protein and mRNA) and correlate to the reduced inotropic effects of beta-adrenoceptor agonists and of cAMP-PDE inhibitors. Gi alpha-coupled m-cholinoceptors and A1-adrenergic receptors are unchanged in density and affinity. Stimulation of these receptors resulted in an unchanged antiadrenergic effect on force of contraction. In conclusion, a downregulation of beta 1 AR and an increase of Gi alpha have been observed as signal transduction alteration in failing human myocardium. These alterations are due to alterations of gene expression in the failing heart and are related to a defective regulation of force of contraction in heart failure.
受体 - G蛋白调节的腺苷酸环化酶活性改变被认为是导致衰竭的人类心脏收缩功能障碍的重要改变。最近的实验表明，β1 - 肾上腺素能受体（β1AR）密度和mRNA水平降低，而β2 - 肾上腺素能受体和刺激性G蛋白未发生变化（mRNA和蛋白水平）。功能测定表明，腺苷酸环化酶的催化作用在衰竭心肌和非衰竭心肌之间并无差异。抑制性G蛋白增加（百日咳毒素底物、蛋白和mRNA），且与β - 肾上腺素能受体激动剂和cAMP - PDE抑制剂的变力作用降低相关。Giα偶联的M胆碱能受体和A1 - 肾上腺素能受体的密度和亲和力未发生变化。刺激这些受体对收缩力产生的抗肾上腺素能作用未改变。总之，在衰竭的人类心肌中观察到β1AR下调和Giα增加，作为信号转导改变。这些改变是由于衰竭心脏中基因表达的改变，并且与心力衰竭中收缩力的调节缺陷有关。
