Adenosine is an endogenous nucleoside that modulates many physiological processes. Its actions are mediated by interaction with specific cell membrane receptors. Four subtypes of adenosine receptors have been cloned: A1, A2A, A2B, and A3. Significant advancement has been made in the understanding of the molecular pharmacology and physiological relevance of adenosine receptors, but our knowledge of A2B receptors lags behind that of other receptor subtypes. The lack of selective pharmacological probes has hindered research in this area. Perhaps because of their lower affinity for adenosine compared with other receptors, it is often assumed that A2B receptors are a low-affinity version of the A2A receptor and are of lesser physiological relevance. It has been only recently that potentially important functions have been discovered for the A2B receptor, prompting a renewed interest in this receptor type. It is also recently recognized that A2B receptors are coupled to intracellular pathways different from those of A2A receptors, a finding that may provide the basis for their distinct physiological role. A2B receptors have been implicated in mast cell activation and asthma, vasodilation, regulation of cell growth, intestinal function, and modulation of neurosecretion. We try to review the recent advances made in the study of A2B receptors and a Address for correspondence: Italo Biaggioni, Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN 37232-2195. Dr. Feoktistov is the recipient of an American Lung Association Research Grant Award and an Asthma and Allergy Foundation of America Investigator Grant Award and is supported also by NIH grants RR00095 and R29HL55596.

Abbreviations: alloxazine, 2, 4-dioxobenzo [g] pteridine; ATP, adenosine 5c-triphosphate; cAMP, adenosine 3c, 5c-cyclic monophosphate; cDNA, complementary deoxyribonucleic acid; CGS 21680, 4-[(N-ethyl-5-carbamoyladenos-2-yl)-aminoethyl]-phenylpropionic acid; CHO, Chinese hamster ovary; CPA, N6-cyclopentyladenosine; DPCPX, 1, 3-dipropyl-8-cyclopentylxanthine; DPSPX, 1, 3-dipropyl-8-(p-sulfophenyl) xanthine; EC50, concentration that produces half-maximal effect; enprofylline, 3-n-propylxanthine; HEL, human erythroleukemia; IB-MECA, N6-(3-iodobenzyl)-N-methyl-5-carbamoyladenosine; IgE, immunoglobulin E; IL-8, interleukin-8; KB, dissociation constant of antagonist-receptor complex; L-249313, 6-carboxymethyl-5, 9-dihydro-9-methyl-2-phenyl-[1, 2, 4]-triazolo-{5, 1-a}-[2, 7]-naphthyridine; L-268605, 3-(4-methoxyphenyl)-5-amino-7-oxo-thiazolo-[3, 2]-pyrimidine; L-NAME, NG-nitro-L-arginine methyl ester; mRNA, messenger ribonucleic acid; MRS 1067, 3, 6-dichloro-2-isopropyloxy-4-methylflavone; MRS 1097, 3, 5-diethyl 2-methyl, 6-phenyl-4-[2-[phenyl-(trans)-vinyl]-1, 4 () dihydropyiridine-3, 5-dicarboxylate; MRS 1191, 3-ethyl 5-benzyl 2-methyl-phenylethynyl-6-phenyl-1, 4 () dihydropyridine-3, 5-dicarboxylate; MRS 1222, 3, 5-diethyl 2-methyl-4-[2-(4-nitrophenyl)-(E)-vinyl-6-phenyl-1, 4-()-dihydropyridine-3, 5-dicarboxylate; NECA, 5-N-ethylcarboxamidoadenosine; NO, nitric oxide; R-PIA,(R)-N6-phenylisopropyladenosine; S-PIA,(S)-N6-phenylisopropyladenosine; SCH 58261, 5-amino-7-(phenylethyl)-2-(1-furyl)-pyrazolo [4, 3-e]-1, 2, 4-triazolo [1, 5-c] pyrimidine; WRC-0571, C8-(N-methylisopropyl)-amino-N6-(5-endohydroxy)-endonorbornan-2-yl-9-methyladenin; XAC, xanthine amine congener; ZM 241385, 4-(2-[7-amino-2-) 2-furyl (triazolo {2, 3-a}-[1, 3, 5] triazin-5-ylamino] ethyl) phenol.