Adenosine A_2B receptor (A_2BR)

Adenosine A_2B receptor (A_2BR) is a low-affinity adenosine receptor that becomes functionally important when extracellular adenosine rises during inflammation, ischemia, or tissue injury^[1][2]. Mechanistically, A_2BR couples mainly to G_αs, elevates cAMP, and can also engage G_αq and MAPK pathways that regulate cytokine production, barrier responses, fibrosis, and cell metabolism^[3][4]. In acute inflammatory models, A_2BR signaling limits vascular adhesion, leukocyte recruitment, pulmonary neutrophilia, cytokine release, and ventilator-induced lung injury^[2][5]. In chronic lung injury models, selective A_2BR antagonism with CVT-6883 reduced pulmonary inflammation, fibrosis, and alveolar airspace enlargement, indicating context-dependent disease relevance^[3]. Compared with A_2AR, A_2BR has lower adenosine affinity, and extracellular loop 2 contributes to this A_2A/A_2B affinity distinction^[1][6]. For experimental applications, BAY 60-6583 activates A_2BR-dependent epithelial barrier repair and astrocyte glycolytic signaling, whereas PSB-603 and related xanthines provide selective antagonist tools for receptor labeling and functional blockade^[4][7][8].