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ALTERATIONS OF BETA-ADRENOCEPTOR-G-PROTEIN-REGULATED ADENYLYL-CYCLASE IN HEART-FAILURE

被引：75
作者：
BOHM, M
机构：
[1] Klinik III für Innere Medizin der Universität zu Köln, Köln, 50924
来源：
MOLECULAR AND CELLULAR BIOCHEMISTRY | 1995年 / 147卷 / 1-2期
关键词：
ADENYLYL CYCLASE; BETA-ADRENOCEPTORS; G-PROTEINS; HEART FAILURE; CARDIOMYOPATHY;
D O I：
10.1007/BF00944795
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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 A(1)-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.
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页码：147 / 160
页数：14
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