Adenosine A(2a) receptors of human circulating blood elements

Recent studies have clearly shown that the adenosine A(2A) receptors are pr esent in a variety of peripheral tissues, including smooth muscle cells, he art muscle and coronary arteries, and human circulating blood elements. Thi s paper reviews the studies performed by our research group on the A(2A) re ceptors on human platelets, lymphocytes, and neutrophils. Affinity and pote ncy of typical adenosine receptor ligands were compared in binding and func tional studies as adenylyl cyclase, aggregation, and superoxide anion produ ction assays. Saturation experiments, performed by using the selective A(2A ) adenosine receptor antagonist [H-3]SCH 58261 (5-amino-7-(2-phenylethyl)-2 -(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5c] pyrimidine) revealed a si ngle class of binding sites in all different preparations examined with aff inity values in the nanomolar range (0.85-1.34 nM) and Bmax values ranging from 35 to 80 fmol/mg protein. Competition experiments showed that the pote ncy order of agonists and antagonists studied was similar in all human circ ulating blood elements. In the functional assays, the same compounds exhibi ted a rank order of potency identical to that observed in binding experimen ts. Moreover, an excellent rank order correlation was found between cAMP ac cumulation, aggregation, and superoxide anion production data by adenosine receptor agonists and antagonists examined. Thermodynamic data indicated th at [H-3]SCH 58261 binding to human lymphocytes and neutrophils is entropy a nd enthalpy driven, a finding in agreement with the thermodynamic behaviour of antagonists binding to rat striatal A(2A) adenosine receptors. Drug Dev . Res. 45:253-260, 1998. (C) 1998 Wiley-Liss, Inc.