Gi-protein-coupled β 1-adrenergic receptor: re-understanding the selectivity of β 1-adrenergic receptor to G protein

Abstract

β ₁-adrenergic receptor (β ₁-AR), a member in the family of G-protein-coupled receptors, is a transmembrane receptor of great significance in the heart. Physiologically, catecholamines activate β ₁-AR to initiate a positive chronotropic, inotropic, and dromotropic change. It is believed that β ₁-AR couples to Gs protein and transmits the signal through second messenger cAMP. However, increasing research shows that β ₁-AR can also bind with Gi protein in addition to Gs. When β ₁-AR-Gi is biasedly activated, cardioprotective effects are introduced by the activated cGMP-protein kinase G (PKG) pathway and the transactivation of epidermal growth factor receptor (EGFR) pathway. The discovery of β ₁-AR-Gi signaling makes us reconsider the selectivity of G protein with regard to β ₁-AR, which also provides new ideas for the treatment of heart diseases. This review summarizes the discovery of β ₁-AR-Gi pathway, including the evidence that supports β ₁-AR's capability to couple Gi, details of the transduction process and functions of the β ₁-AR-Gi signaling pathway.

Keywords: G protein switch; Gi protein; cardioprotective effect; signal transduction; β-adrenergic receptor.

Figure 1

Different signaling pathways, same cardioprotective effects EGFR-ERK pathway and NOS3-cGMP-PKG signaling can be activated by biased activation of β 1-AR-Gi pathway. Both signaling pathways play a role in cardiac protection.