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Alterations of β-adrenoceptor-G-protein-regulated adenylyl cyclase in heart failure

  • Part III: Signal Transduction
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Abstract

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 β1-adrenoceptor(α1AR) density and mRNA levels are reduced, while β2-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 β-adrenoceptor agonists and of CAMP-PDE inhibitors. Giα-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 β1-AR and an increase of Giα 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.

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    Michael Böhm

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Böhm, M. Alterations of β-adrenoceptor-G-protein-regulated adenylyl cyclase in heart failure. Mol Cell Biochem 147, 147–160 (1995). https://doi.org/10.1007/BF00944795

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