Adenosine modulates different functional activities in many cells of the gastrointestinal tract; some of them are believed to be mediated by interaction with its four
G protein-coupled receptors. The renewed interest in the
adenosine A2B receptor (A2BR) subtype can be traced by studies in which the introduction of new genetic and chemical tools has widened the pharmacological and structural knowledge of this receptor as well as its potential
therapeutic use in
cancer and
inflammation- or
hypoxia-related pathologies. In the
acid-secreting parietal cells of the gastric mucosa, the use of various radioligands for
adenosine receptors suggested the presence of the A2
adenosine receptor subtype(s) on the cell surface. Recently, we confirmed A2BR expression in native, nontransformed parietal cells at rest by using flow cytometry and confocal microscopy. In this study, we show that A2BR is functional in primary rabbit gastric parietal cells, as indicated by the fact that agonist binding to A2BR increased
adenylate cyclase activity and
acid production. In addition, both
acid production and radioligand binding of
adenosine analogs to isolated cell membranes were potently blocked by selective A2BR antagonists, whereas
ligands for A1, A2A, and A3
adenosine receptors failed to abolish activation. We conclude that rabbit gastric parietal cells possess functional A2BR
proteins that are coupled to Gs and stimulate HCl production upon activation. Whether
adenosine- and A2BR-mediated functional responses play a role in human gastric pathophysiology is yet to be elucidated.