Cardiac β₃ -adrenoceptors-A role in human pathophysiology?

As β₃ -adrenoceptors were first demonstrated to be expressed in adipose tissue they have received much attention for their metabolic effects in obesity and diabetes. After the existence of this subtype had been suggested to be present in the heart, studies focused on its role in cardiac function. While the presence and functional role of β₃ -adrenoceptors in the heart has not uniformly been detected, there is a broad consensus that they become up-regulated in pathological conditions associated with increased sympathetic activity such as heart failure and diabetes. When detected, the β₃ -adrenceptor has been demonstrated to mediate negative inotropic effects in an inhibitory G protein-dependent manner through the NO-cGMP-PKG signalling pathway. Whether these negative inotropic effects provide protection from the adverse effects induced by overstimulation of β₁ /β₂ -adrenoceptors or in themselves are potentially harmful is controversial, but ongoing clinical studies in patients with congestive heart failure are testing the hypothesis that β₃ -adrenceptor agonism has a beneficial effect. LINKED ARTICLES: This article is part of a themed section on Adrenoceptors-New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc.