Alternative titles; symbols
HGNC Approved Gene Symbol: ADORA2B
Cytogenetic location: 17p12 Genomic coordinates (GRCh38): 17:15,850,362-15,975,746 (from NCBI)
Using degenerate primers to amplify cDNAs encoding G protein-coupled receptors from a human hippocampus cDNA library, Pierce et al. (1992) cloned full-length ADORA2B, which they called A2B. The deduced 328-amino acid protein contains 7 putative transmembrane domains, characteristic of G protein-coupled receptors, and 2 N-glycosylation sites in the second extracellular loop.
By Northern blot analysis, Strohmeier et al. (1995) detected wide expression of 2 A2B transcripts in the human alimentary tract, with highest expression throughout the colon and in gastric atrium, esophagus, and appendix. Much lower expression was detected in fundus and ileum.
Kataoka et al. (2012) found that mouse A2br mRNA and protein were expressed in a subset of taste bud cells of the posterior (circumvallate, foliate), but not anterior (fungiform, palate), taste fields. They noted that this pattern of expression is more restricted than that observed in macaque. Double-labeling revealed that A2b was coexpressed with the sweet-sensitive type II cell marker G-alpha-14 (GNA14; 604397).
Townsend-Nicholson et al. (1995) used PCR screening of somatic cell hybrids and fluorescence in situ hybridization to map the adenosine A2b receptor subtype to 17p12-p11.2. Since several reports had indicated the existence of novel adenosine receptor subtypes, they suggested that signals observed on chromosome 1 at position 1q21.3-q23 and a signal observed at 10q25.3-q26.3 (see HISTORY) may represent further A2 adenosine receptor subtypes. The signal at 1q21.3-q23 has been designated a pseudogene (ADORA2BP1).
Pierce et al. (1992) showed that human A2B expressed in Chinese hamster ovary cells stimulated cAMP accumulation in response to a low-affinity A2B-selective agonist, but not to A1 (ADORA1; 102775)- or A2A (ADORA2A; 102776)-selective agonists.
Strohmeier et al. (1995) found that endogenous A2B expressed in a human intestinal epithelial cell line responded to adenosine and increased intracellular cAMP levels via coupling to adenylate cyclase and protein kinase A (see 188830). Response to adenosine was greater on the basolateral surface than the apical surface.
Corset et al. (2000) showed that DCC (120470) interacts with the membrane-associated adenosine A2b receptor, a G protein-coupled receptor that induces cAMP accumulation on binding adenosine. They determined that adenosine A2b receptor is actually a netrin-1 (601614) receptor and induces cAMP accumulation on binding netrin-1 and that netrin-dependent outgrowth of dorsal spinal cord axons directly involves A2b. Corset et al. (2000) concluded that the growth-promoting function of netrin-1 may require a receptor complex containing DCC and A2b.
Stein et al. (2001) demonstrated that netrin-1 binds DCC and that the DCC cytoplasmic domain fused to a heterologous receptor ectodomain can mediate guidance through a mechanism involving derepression of cytoplasmic domain multimerization. Activation of the adenosine A2B receptor, proposed to contribute to netrin effects on axons, is not required for rat commissural axon outgrowth or Xenopus spinal axon attraction to netrin-1. Thus, Stein et al. (2001) concluded that DCC plays a central role in netrin signaling of axon growth and guidance independent of A2B receptor activation. Note that an expression of concern was published for the article by Stein et al. (2001).
Von Gall et al. (2002) demonstrated that cycling expression of the clock gene Period-1 (602260) in rodent pituitary cells depends on the heterologous sensitization of the adenosine A2B receptor, which occurs through the nocturnal activation of melatonin mt1 receptors (600665). Eliminating the impact of the neurohormone melatonin simultaneously suppresses the expression of Period-1 and evokes an increase in the release of pituitary prolactin. Von Gall et al. (2002) concluded that their observations expose a mechanism by which 2 convergent signals interact within a temporal dimension to establish high-amplitude, precise, and robust cycles of gene expression.
Mino et al. (2001) studied the efficacy of specific adenosine receptor antagonists in reducing retinal neovascularization in a mouse pup model of oxygen-induced retinopathy. They used a nonselective adenosine receptor antagonist as well as 3 classes of selective antagonists (A1, A2A, and A2B). They found that the 2 A2B-selective antagonists used inhibited oxygen-induced retinal neovascularization in vivo. Mino et al. (2001) concluded that these moieties might provide a basis for developing pharmacologic therapies for the treatment of proliferative retinopathies.
Kataoka et al. (2012) found that knockout of A2b in mice ablated responses of glossopharyngeal nerves to both sucrose and synthetic sweeteners, suggesting that A2br functions in transduction and transmission of sweet taste information.
Rivkees and Reppert (1992) characterized the pharmacologic properties of a cDNA clone for A2b adenosine receptor in stably transfected CHO cells by examining cAMP responses to drug treatments. Libert et al. (1991), who used the gene symbol ADORA2L, mapped the gene to 10q25.3-q26.3 by in situ hybridization.
Corset, V., Nguyen-Ba-Charvet, K. T., Forcet, C., Moyse, E., Chedotal, A., Mehlen, P. Netrin-1-mediated axon outgrowth and cAMP production requires interaction with adenosine A2b receptor. Nature 407: 747-750, 2000. [PubMed: 11048721] [Full Text: https://doi.org/10.1038/35037600]
Kataoka, S., Baquero, A., Yang, D., Shultz, N., Vandenbeuch, A., Ravid, K., Kinnamon, S. C., Finger, T. E. A2BR adenosine receptor modulates sweet taste in circumvallate taste buds. PLoS One 7: e30032, 2012. Note: Electronic Article. [PubMed: 22253866] [Full Text: https://doi.org/10.1371/journal.pone.0030032]
Libert, F., Passage, E., Parmentier, M., Simons, M.-J., Vassart, G., Mattei, M.-G. Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor. Genomics 11: 225-227, 1991. Note: Erratum: Genomics 23: 305 only, 1994. [PubMed: 1662665] [Full Text: https://doi.org/10.1016/0888-7543(91)90125-x]
Mino, R. P., Spoerri, P. E., Caballero, S., Player, D., Belardinelli, L., Biaggioni, I., Grant, M. B. Adenosine receptor antagonists and retinal neovascularization in vivo. Invest. Ophthal. Vis. Sci. 42: 3320-3324, 2001. [PubMed: 11726639]
Pierce, K. D., Furlong, T. J., Selbie, L. A., Shine, J. Molecular cloning and expression of an adenosine A2b receptor from human brain. Biochem. Biophys. Res. Commun. 187: 86-93, 1992. [PubMed: 1325798] [Full Text: https://doi.org/10.1016/s0006-291x(05)81462-7]
Rivkees, S. A., Reppert, S. M. RFL9 encodes an A2b adenosine receptor. Molec. Endocr. 6: 1598-1604, 1992. [PubMed: 1333049] [Full Text: https://doi.org/10.1210/mend.6.10.1333049]
Stein, E., Zou, Y., Poo, M., Tessier-Lavigne, M. Binding of DCC by netrin-1 to mediate axon guidance independent of adenosine A2B receptor activation. Science 291: 1976-1982, 2001. Note: Expression of Concern: Science 378: 1284 only, 2022. [PubMed: 11239160] [Full Text: https://doi.org/10.1126/science.1059391]
Strohmeier, G. R., Reppert, S. M., Lancer, W. I., Madara, J. L. The A2b adenosine receptor mediates cAMP responses to adenosine receptor agonists in human intestinal epithelia. J. Biol. Chem. 270: 2387-2394, 1995. [PubMed: 7836474] [Full Text: https://doi.org/10.1074/jbc.270.5.2387]
Townsend-Nicholson, A., Baker, E., Sutherland, G. R., Schofield, P. R. Localization of the adenosine A2b receptor subtype gene (ADORA2B) to chromosome 17p11.2-p12 by FISH and PCR screening of somatic cell hybrids. Genomics 25: 605-607, 1995. [PubMed: 7790006] [Full Text: https://doi.org/10.1016/0888-7543(95)80074-v]
von Gall, C., Garabette, M. L., Kell, C. A., Frenzel, S., Dehghani, F., Schumm-Draeger, P.-M., Weaver, D. R., Korf, H.-W., Hastings, M. H., Stehle, J. H. Rhythmic gene expression in pituitary depends on heterologous sensitization by the neurohormone melatonin. Nature Neurosci. 5: 234-238, 2002. [PubMed: 11836530] [Full Text: https://doi.org/10.1038/nn806]