Adenosine Receptor A2a

        The A2b adenosine receptor (A2aAR) has been cloned from a variety of species including canine, rat, and human (Olah and Stiles, 1995). A2aARs are typically larger than the A1ARs and range in size from 410- 412 amino acids corresponding to a protein of about 45, 000 daltons. The most  striking difference between A1 and A2a is in the size of the carboxyl tail; the A2a tail being much longer than the carboxyl terminal tail found in A1ARs. The presence in the tail of multiple serines and threonines suggests that this region may be important in the regulation of the receptor by phosphory;lation following agonist stimulation. The A2b adenosine receptor was cloned from a human hippocampal cDNA library in 1992 (Furlong et al., 1992). This receptor is positively coupled to adenylate cyclase and displays high affinity binding for the A_2a specific agonist CGS21680.

        This, however, seems unlikely, since mutated canine A2a in which stop codons were inserted at amino acids 309 or 316 lead to markedly truncated carboxyl terminal tails as defined by photoaffinity labeling. These mutations failed to alter either the binding of ligands to this receptor or the receptor's ability to stimulate adenylyl cyclase. Further studies will be needed to understand the importance of this unique structural feature of A2a receptors.

Site- directed mutagenesis studies

          Site- directed mutagenesis studies have now been undertaken with the human A2aAR. Kim et al. (1995) has studied a wide range of individual point mutations and their effect on agonist and antagonist binding. In order to document whether there were differences between actual loss in binding and expression of the receptor on the surface, they have incorporated a specific hemagglutinin epitope tag into their receptor. So they can identify the expressed protein immunologically in the cell membranes by the use of monoclonal antibodies. Following expression of the tagged receptors, they studied the functional properties of the mutant receptors by measuring stimulation of adenylyl cyclase amd also determined specific binding using ³H CGS21680 (agonist) and ³H XAC (antagoinst) radioligands. They explored a number of regions of the receptor and found that mutation of the histidines to alanine in transmembrane domain 6 and 7 led to loss of both agonist and antagonist binding. In addition mutation to alanine of Phe- 182 in transmembrane domain 5, Asp-253 in transmembramne domain 6, Ile- 274 and Ser- 281 in transmembrane 7, in each led to loss of both agonist and antagonist binding. Many of these same regions were found to be important for binding of agonists in the A1AR, thus highlighting the similarity of A1 and A2 receptors in terms of agonist and antagonist interactions. In addition, it was found that the hydroxyl group of Ser- 277 was required for high- affinity of agonist but was not important for antagonist binding. This was the  first detailed study of the A2a receptor and the authors have developed a model in which agonists and antagonists might dock into the receptor

Databases of A2a Adenosine Receptor

Phylogenetic Tree 

For up to 20 representative sequences for A2a and A2b adenosine receptors

Modelling of Adensoine A2 Receptor!!