title: Stimulation of gastric acid secretion by rabbit parietal cell A(2B) adenosine receptor activation.
abstract: 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.
authors.affiliation: Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU, Leioa, Spain rosamaria.arin@ehu.eus.
authors.forename: Rosa María
authors.initials: RM
authors.lastname: Arin
authors.affiliation: Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU, Leioa, Spain.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Vallejo
authors.affiliation: Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU, Leioa, Spain.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Rueda
authors.affiliation: Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU, Leioa, Spain.
authors.forename: Olatz
authors.initials: O
authors.lastname: Fresnedo
authors.affiliation: Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU, Leioa, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Ochoa
mesh_terms: D000818:Animals; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005744:Gastric Acid / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D010295:Parietal Cells, Gastric / Q000378:metabolism*; D011817:Rabbits; D043704:Receptor, Adenosine A2B / Q000378:metabolism*
chemical_list: D043704:Receptor, Adenosine A2B
keywords: Gs protein-coupled A2B adenosine receptor; gastric acid secretion; parietal cell