Adenosine A2B Receptor: From Cell Biology to Human Diseases

Abstract

Extracellular adenosine is a ubiquitous signaling molecule that modulates a wide array of biological processes. Recently, significant advances have been made in our understanding of A2B adenosine receptor (A2BAR). In this review, we first summarize some of the general characteristics of A2BAR, and then we describe the multiple binding partners of the receptor, such as newly identified α-actinin-1 and p105, and discuss how these associated proteins could modulate A2BAR's functions, including certain seemingly paradoxical functions of the receptor. Growing evidence indicates a critical role of A2BAR in cancer, renal disease, and diabetes, in addition to its importance in the regulation of vascular diseases, and lung disease. Here, we also discuss the role of A2BAR in cancer, renal disease, and diabetes and the potential of the receptor as a target for treating these three diseases.

Focusing on Adenosine Receptors as a Potential Targeted Therapy in Human Diseases

“…A 2B AR is highly expressed in tumor cells and promotes tumor cell proliferation; hence, it might serve as a target for novel therapies or combination therapies for cancer [249]. A 2B AR promoted tumor-inducing M2 macrophages (tumor-associated macrophages); however, it had less effect on decreasing cancer cell proliferation and metastasis and inducing proapoptotic effects [250].…”

Guanosine-Based Nucleotides, the Sons of a Lesser God in the Purinergic Signal Scenario of Excitable Tissues

“…Then, firstly the extracellular pool of adenosine is reduced mainly through nucleoside transporters that transport it back into the cell; secondly, adenosine is deaminated to inosine through the action of adenosine deaminase. Finally, adenosine could be deactivated by its phosphorylation in AMP through the action of adenosine kinase [6]. Adenosine acts via specific receptors that are divided into at least four categories: A(1), A(2A), A(2B) and A(3) [7].…”

Targeting A2 adenosine receptors in cancer

“…A2b receptor can be expressed in a variety of tissue such as vasculature, brain, intestines and on many cell types including mostly immune cells such as mast cells, neutrophils, dendritic cells, macrophages and lymphocytes, but also other cells like endothelial cells, astrocytes and neurons 46 . Its widespread expression as well as its diversity in signaling places A2b as an important player in numerous diseases such as vascular diseases, chronic and acute lung disease, renal disease and diabetes and cancer 46 . Many studies have demonstrated A2b receptor to be pro‐tumorigenic.…”