Cagnina RE, Ramos SI, Marshall MA, Wang G, Frazier CR, Linden J
Adenosine A2B receptors are highly expressed on murine type II alveolar epithelial cells. [JOURNAL ARTICLE]
Am J Physiol Lung Cell Mol Physiol 2009 Jul 2.
The adenosine A2B receptor (A2BR) has a wide tissue distribution that includes fibroblasts, endothelial and epithelial cells. The recent generation of an A2BR(-/-) mouse constructed with a beta-galactosidase (beta-gal) reporter gene under control of the endogenous promoter has provided a valuable tool to quantify A2BR promoter activity (29). To determine the sites of expression of the A2B receptor in the mouse lung, histologic and flow-cytometric analysis of beta-galactosidase reporter gene expression in various lung cell populations was performed. The major site of A2BR promoter activity was found to be the type II alveolar epithelial cells (AECs), identified by co-expression of pro-surfactant protein C, with relatively less expression in alveolar macrophages, bronchial epithelial cells, and cells of the vasculature. Highly purified type II alveolar epithelial cells were prepared by fluorescence-activated sorting of eGFP-positive cells from transgenic mice expressing eGFP under control of the surfactant protein C promoter (21). The type II cells expressed 89-fold higher A2BR mRNA than pulmonary leukocytes, and the A2BR was shown to be functional, as treatment of purified type II AECs with the non-specific adenosine receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA) induced an increase in intracellular cAMP greater that the beta-adrenergic agonist, isoproterenol, that was inhibited completely following treatment by ATL-802, a novel, highly potent (Ki = 8.6 nM) and selective (>900 fold over other adenosine receptor subtypes) antagonist of the mouse A2BR. Key words: lung, beta-galactosidase, G-protein coupled receptor, cAMP.
More from this journal |
