β₃‐AR and the vertebrate heart: a comparative view

Abstract

Recent cardiovascular research showed that, together with β1- and β2-adrenergic receptors (ARs), β3-ARs contribute to the catecholamine (CA)-dependent control of the heart. β3-ARs structure, function and ligands were investigated in mammals because of their applicative potential in human cardiovascular diseases. Only recently, the concept of a β3-AR-dependent cardiac modulation was extended to non-mammalian vertebrates, although information is still scarce and fragmentary. β3-ARs were structurally described in fish, showing a closer relationship to mammalian β1-AR than β2-AR. Functional β3-ARs are present in the cardiac tissue of teleosts and amphibians. As in mammals, activation of these receptors elicits a negative modulation of the inotropic performance through the involvement of the endothelium endocardium (EE), Gi/0 proteins and the nitric oxide (NO) signalling. This review aims to comparatively analyse data from literature on β3-ARs in mammals, with those on teleosts and amphibians. The purpose is to highlight aspects of uniformity and diversity of β3-ARs structure, ligands activity, function and signalling cascades throughout vertebrates. This may provide new perspectives aimed to clarify the biological relevance of β3-ARs in the context of the nervous and humoral control of the heart and its functional plasticity.

Targeting β3-Adrenergic Receptors in the Heart: Selective Agonism and β-Blockade

“…Moreover, all the studies concerning β 3 AR function have not been focused on similar cell types, and the agonist and the doses used are significantly different between most studies. 14 , 15 Another important difference is represented by the experimental model used in key studies. 15 In fact, it is known that in the mouse, the gene encoding for the β 3 AR undergoes alternative splicing and gives rise to β 3 aAR and β 3 bAR variants.…”

“… 14 , 15 Another important difference is represented by the experimental model used in key studies. 15 In fact, it is known that in the mouse, the gene encoding for the β 3 AR undergoes alternative splicing and gives rise to β 3 aAR and β 3 bAR variants. 16 , 17 These 2 β 3 AR isoforms are coupled to adenylyl cyclase stimulatory Gα (Gαs) or to the inhibitory Gα (Gαi) protein subunits (β 3 bAR), or exclusively to the Gαs protein (β 3 aAR).…”

How palmitoylation affects trafficking and signaling of membrane receptors

“…These three receptor subtypes are GPCR and interact with different subunits of Gα via the third inner loop of every β-AR (Baker, 2014). The three β-AR are expressed in the heart (Imbrogno et al, 2015), and in the lung (Nilsson et al, 2020), but the β1 subtype is the prominent one (Lohse et al, 2003).…”

NO, CO and H2S: What about gasotransmitters in fish and amphibian heart?

“…In the in vitro perfused R. esculenta heart , both positive and negative effects elicited by ACh on contractility are mediated by NO and involve the EE . Also the cardiodepression induced by BRL 37344 ‐dependent β 3 ‐AR activation and by low concentrations (0.01 nmol/L) of endothelin‐1 (ET‐1) requires the recruitment of the EE/NOS/NO pathway . In the second case, this occurs via activation of endothelial ETB receptors .…”