Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, 1994: SIGNALLING PATHWAYS IN CARDIAC FAILURE

1. Cardiac failure in humans and in animal models is associated with a marked desensitization of the catecholamine signalling pathway. 2. β₁‐ and β₂‐ and possibly β₃‐adrenoceptors (β‐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 β‐AR leads to a rapid loss of β₂‐AR whereas heart failure in humans is associated with a loss of β₁‐AR or β₁‐AR and β₂AR. 3. Desensitization is also associated with phosphorylation of β‐AR by β‐AR kinase β‐ARK) and uncoupling of receptors from the signalling pathway. β‐ARK but not β‐arrestin activity and mRNA are markedly increased in heart failure. 4. Chronic β‐AR stimulation and heart failure are associated with increases in Giα but little if any change in Gsα. 5. The roles of βm̀ subunits of G‐proteins, adenylate cyclase subtypes and cAMP dependent protein kinase A in heart failure are unclear at present.