Signalling pathways in cardiac failure

Clinical and Experimental Pharmacology & Physiology
R J SummersP Molenaar

Abstract

1. Cardiac failure in humans and in animal models is associated with a marked desensitization of the catecholamine signalling pathway. 2. Beta 1- and beta 2- and possibly beta 3-adrenoceptors (beta-AR) are found in the hearts of humans and common laboratory animals such as rats and guinea-pigs. In rats and guinea-pigs chronic stimulation of cardiac beta-AR leads to a rapid loss of beta 2-AR whereas heart failure in humans is associated with a loss of beta 1-AR or beta 1-AR and beta 2-AR. 3. Desensitization is also associated with phosphorylation of beta-AR by beta-AR kinase (beta-ARK) and uncoupling of receptors from the signalling pathway. Beta-ARK but not beta-arrestin activity and mRNA are markedly increased in heart failure. 4. Chronic beta-AR stimulation and heart failure are associated with increases in Gi alpha but little if any change in Gs alpha. 5. The roles of beta gamma subunits of G-proteins, adenylate cyclase subtypes and cAMP dependent protein kinase A in heart failure are unclear at present. beta-ARK - beta-adrenoceptor kinase AR - adrenoceptor G-protein - GTP binding protein

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Citations

Oct 12, 2000·Cellular Signalling·S ChakrabortiG Shaw
May 5, 1998·Fundamental & Clinical Pharmacology·A ChahdiY Landry
Jul 14, 2016·Expert Opinion on Therapeutic Targets·Antonino TuttolomondoAntonio Pinto
Feb 27, 2003·The Journal of Pharmacology and Experimental Therapeutics·Imène Tabbi-AnneniAlain Grynberg

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