Ligands for A2B Adenosine Receptor Subtype

Pier      Giovanni Baraldi; Romeo      Romagnoli; Delia      Preti; Francesca      Fruttarolo; Maria      DoraCarrion; Mojgan      Aghazadeh Tabrizi

doi:10.2174/092986706779010306

Abstract

Adenosine is a naturally occurring nucleoside, which exerts its biological effects by interacting witha family of adenosine receptors known as A1, A2A, A2B, and A3. The A2B subtype is a low affinity receptor,which couples to stimulation of adenylyl cyclase and also leads to a rise in intracellular calcium modulatingimportant physiological processes. Adenosine exhibiting activity at this subtype is at concentrations greaterthan 10 μM. The A2B receptors show a ubiquitous distributions, the highest levels are present in cecum, colonand bladder, followed by blood vessels, mast cells and lung. Through A2B receptors, adenosine also regulatesthe growth of smooth muscle cell populations in blood vessels, cell growth, intestinal function, inhibition ofTumor Necrosis Factor (TNF-α), vascular tone, and inflammatory processes such as diarrhea and asthma. Potent and selective adenosine agonists are the result of modifications of the parent ligand adenosine bysubstitution, namely at N6 or C2 position of the purine heterocycle or at the 5 position of the ribose moiety.5-N-ethylcarboxamidoadenosina (NECA) is one of the most potent A2B adenosine receptor agonist. Classicalantagonists for A2B adenosine receptors are xanthine analogues obtained from multiple substitutions of theparent heterocycle by C8 substitution combined with N1 and N3 (and sometimes N7) substitutions.

Keywords: Adenosine, A2B receptors, A2B agonists, A2B antagonists, Xanthines, Inflammation, Asthma

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