The negative inotropic action of catecholamines: Role of β3-adrenoceptors

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Abstract
There is now evidence for the involvement of four β-adrenoceptor populations in the regulation of cardiac function by catecholamines. β1- and β2-adrenoceptor stimulation classically produces an increase in contractility. A fourth β-adrenoceptor, as yet uncloned and designated provisionally as a β4-adrenoceptor, also mediates a positive inotropic effect. β3-adrenoceptors, which had been cloned at the end of the eighties, has been extensively studied as a potential target for antiobesity and antidiabetic drugs. Its characterization in the heart has opened new fields of investigations for the understanding of the cardiac adrenergic regulation. This review describes the cardiac electrical and mechanical effects induced by β3-adrenoceptor stimulation in different species (including human), as well as the signaling pathway. It also analyzes the role of these receptors in the abnormal responsiveness of catecholamines in heart failure.Key words: beta-adrenoceptor, heart, contractility, signaling pathway, heart failure.