Introduction of ADORA3

Adenosine receptor A₃ (ADORA3) is a protein that in humans is encoded by the ADORA3 gene. The gene contains 2 exons separated by a single intron of about 2.2 kb. The A₃ adenosine receptor is found to be expressed in Chinese hamster ovary cells and the agonist binds to membrane preparations inhibited cAMP accumulation. Pharmacologic characterization with several adenosine receptor agonists and xanthine antagonists showed that the human receptor is more similar to the sheep A₃ adenosine receptor than to the rat A₃ adenosine receptor. Adenosine released during cardiac ischemia exerts an effective, protective effect in the heart.

Function of ADORA3 Membrane Protein

The adenosine A₃ receptor is expressed on cardiac ventricular cells, and its activation protects the ventricular heart cell against injury during a subsequent exposure to ischemia. The cardiac adenosine A₃ receptor mediates a sustained cardioprotective function and it represents a new target for cardiac therapeutic. Cardiac atrial cells lack native A₃ receptors and exhibited a shorter duration of cardioprotection than did ventricular cells. Transfection of atrial cells with cDNA encoding the human ADORA3 results in a sustained A₃ agonist-mediated cardioprotection. Numerous studies have demonstrated the role of A₃ adenosine receptor and signaling pathways in the multiple aspects of the tumor. There is also research about the function of ADORA3 in the biological processes of cancer stem cells (CSCs).

Fig.1 Schematic representation of second messengers and intracellular signaling pathways, downstream targets, mediated by A3ARs stimulation. (Borea, 2015)

Application of ADORA3 Membrane Protein in Literature

1. Cao H. L., et al. Cordycepin induces apoptosis in human bladder cancer cells via activation of A3 adenosine receptors. Tumour Biol. 2017, 39(7): 1010428317706915. PubMed ID: 28714368

This article reports that Cordyceps militaris hot water extracts containing cordycepin decreased T24 cell survival in a dose-dependent manner, which was seemingly mediated by activation of A3 adenosine receptor and the subsequent inactivation of Akt pathways, resulting in increases in cleaved Caspase-3 and apoptosis. Cordyceps militaris hot water extracts containing cordycepin may be a promising treatment for bladder cancer via A3 adenosine receptor activation.

2. Jafari SM., et al. A3 Adenosine Receptor Agonist Inhibited Survival of Breast Cancer Stem Cells via GLI-1 and ERK1/2 Pathway. J Cell Biochem. 2017, 118(9): 2909-2920. PubMed ID: 28230290

Authors in this group investigate the effect of A3AR agonist on breast cancer stem cells (BCSCs). The results show that A₃ adenosine receptor agonist inhibited survival of breast cancer stem cells via GLI-1 and ERK1/2.

3. Joós G., et al. Involvement of adenosine A3 receptors in the chemotactic navigation of macrophages towards apoptotic cells. Immunol Lett. 2017, 183: 62-72. PubMed ID: 28188820

This article reports that adenosine A₃ receptors are involved in the chemotactic navigation of macrophages towards apoptotic cells. Loss of A3Rs did not affect the in vivo clearance of apoptotic thymocytes in the dexamethasone-treated thymus.

4. Yang T., et al. Genetic Abrogation of Adenosine A3 Receptor Prevents Uninephrectomy and High Salt-Induced Hypertension. J Am Heart Assoc. 2016, 5(7). PubMed ID: 27431647

Authors in this group investigate the specific role of the A₃ receptor in cardiovascular diseases. It shows that loss of ADORA3 signaling is strongly protective in this novel mouse model of renal and cardiovascular disease.

5. Wu W., et al. MicroRNA-206 is involved in the pathogenesis of ulcerative colitis via regulation of adenosine A3 receptor. Oncotarget. 2017, 8(1): 705-721. PubMed ID: 27893428

This article demonstrated that miR-206 has a proinflammatory role in UC by downregulating A3AR expression and activating NF-κB signaling.

ADORA3 Preparation Options

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Reference

1. Borea PA, et al. (2015). The A3 adenosine receptor: history and perspectives. Pharmacol Rev. 67(1), 74-102.

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