Adenosine receptors (ARs) comprise a group of G protein-coupled receptors (GPCR) which mediate the physiological actions of adenosine. To date, there are four types of adenosine receptors in humans: A1, A2A, A2B and A3; each is encoded by a different gene. In addition, These receptors have distinct localization, signal transduction pathways and different means of regulation upon exposure to agonists. Among them, A2B receptors, which are coupled to stimulation of adenylyl cyclase and also lead to a rise in intracellular calcium. Moreover, A2B receptors play important roles in controlling vascular tone, cell growth, and gene expression. Xanthine derivatives such as Caffeine and Theophylline act as non-selective antagonists at A1 and A2A receptors and so have the opposite effect to adenosine. Furthermore, these compounds also act as phosphodiesterase inhibitors, which produces additional anti-inflammatory effects. Thus, the adenosine receptors antagonists has the potential for asthma research.

MRS 1754, a p-cyanoanilide Xanthine derivative, is a selective A2B adenosine receptor antagonist. However, MRS 1754 shows very low affinity for A1 and A3 receptors of both humans and rats. This compound binds to recombinant human A2B adenosine receptors in membranes of stably transfected HEK-293 cells. Meanwhile, MRS 1754 is 400-, 245-, and 123-fold more selective for human A2B receptors than human A1/A2A/A3 receptors. In addition, in cells expressing human A2A receptors, MRS 1754 displays low levels of binding to this receptor subtype. MRS 1754 has the potential as an antiasthmatic agent.

In conclusion, MRS 1754 is a potent and selective A2B adenosine receptor antagonist, with antiasthmatic effects.


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