Is the adenosine A2B ‘biased’ receptor a valuable target for the treatment of pulmonary arterial hypertension?

• Published in: Drug discovery today 2018-06, Vol.23 (6), p.1285-1292
• Main Authors: Bessa-Gonçalves, Mafalda, Bragança, Bruno, Martins-Dias, Eduardo, Correia-de-Sá, Paulo, Fontes-Sousa, Ana Patrícia
• Format: Article
• Language: English
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/j.drudis.2018.05.005

•Life-threatening pulmonary arterial hypertension (PAH) has an unmet clinical need.•Adenosine has pleiotropic effects in PAH affected organs, like heart and lungs.•Pathological conditions change coupling of biased-GPCRs to intracellular pathways.•Novel A2B receptor “biased” agonists may be useful in the treatment of PAH. Pulmonary arterial hypertension (PAH) is a maladaptive disorder characterized by increased pulmonary vascular resistance leading to right ventricular failure and death. Adenosine released by injured tissues, such as the lung and heart, influences tissue remodeling through the activation of adenosine receptors. Evidence regarding activation of the low-affinity A2BAR by adenosine points towards pivotal roles of this receptor in processes associated with both acute and chronic lung diseases. Conflicting results exist concerning the beneficial or detrimental roles of the A2B ‘biased’ receptor in right ventricular failure secondary to PAH. In this review, we discuss the pros and cons of manipulating A2BARs as a putative therapeutic target in PAH.