The negative inotropic action of catecholamines: Role of beta(3)-adrenoceptors

There is now evidence for the involvement of four beta-adrenoceptor populat ions in the regulation of cardiac function by catecholamines. beta(1)- and beta(2)-adrenoceptor stimulation classically produces an increase in contra ctility. A fourth beta-adrenoceptor, as yet uncloned and designated provisi onally as a beta(4)-adrenoceptor, also mediates a positive inotropic effect . beta(3)-adrenoceptors, which had been cloned at the end of the eighties, has been extensively studied as a potential target for antiobesity and anti diabetic 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 beta(3)-adrenoceptor stimulation in different species (including human) , as well as the signaling pathway. It also analyzes the role of these rece ptors in the abnormal responsiveness of catecholamines in heart failure.