Recent studies have clearly shown that the adenosine A(2A) receptors are present in a variety of peripheral tissues, including smooth muscle cells, heart muscle and coronary arteries, and human circulating blood elements. This paper reviews the studies performed by our research group on the A(2A) receptors on human platelets, lymphocytes, and neutrophils. Affinity and potency of typical adenosine receptor ligands were compared in binding and functional studies as adenylyl cyclase, aggregation, and superoxide anion production assays. Saturation experiments, performed by using the selective A(2A) adenosine receptor antagonist [3H]SCH 58261 (5-amino-7-(2- phenylethyl)-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5c]pyrimidine) revealed a single class of binding sites in all different preparations examined with affinity 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 potency order of agonists and antagonists studied was similar in all human circulating blood elements. In the functional assays, the same compounds exhibited a rank order of potency identical to that observed in binding experiments. Moreover, an excellent rank order correlation was found between cAMP accumulation, aggregation, and superoxide anion production data by adenosine receptor agonists and antagonists examined. Thermodynamic data indicated that [3H]SCH 58261 binding to human lymphocytes and neutrophils is entropy and enthalpy driven, a finding in agreement with the thermodynamic behaviour of antagonists binding to rat striatal A(2A) adenosine receptors.
Adenosine A2A receptors in human circulating blood elements
VARANI, Katia;GESSI, Stefania;MERIGHI, Stefania;BOREA, Pier Andrea
1998
Abstract
Recent studies have clearly shown that the adenosine A(2A) receptors are present in a variety of peripheral tissues, including smooth muscle cells, heart muscle and coronary arteries, and human circulating blood elements. This paper reviews the studies performed by our research group on the A(2A) receptors on human platelets, lymphocytes, and neutrophils. Affinity and potency of typical adenosine receptor ligands were compared in binding and functional studies as adenylyl cyclase, aggregation, and superoxide anion production assays. Saturation experiments, performed by using the selective A(2A) adenosine receptor antagonist [3H]SCH 58261 (5-amino-7-(2- phenylethyl)-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5c]pyrimidine) revealed a single class of binding sites in all different preparations examined with affinity 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 potency order of agonists and antagonists studied was similar in all human circulating blood elements. In the functional assays, the same compounds exhibited a rank order of potency identical to that observed in binding experiments. Moreover, an excellent rank order correlation was found between cAMP accumulation, aggregation, and superoxide anion production data by adenosine receptor agonists and antagonists examined. Thermodynamic data indicated that [3H]SCH 58261 binding to human lymphocytes and neutrophils is entropy and enthalpy driven, a finding in agreement with the thermodynamic behaviour of antagonists binding to rat striatal A(2A) adenosine receptors.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
