S. Dionisotti et al., LABELING OF A(2A) ADENOSINE RECEPTORS IN HUMAN PLATELETS BY USE OF THE NEW NONXANTHINE ANTAGONIST RADIOLIGAND [H-3] SCH-58261, The Journal of pharmacology and experimental therapeutics, 278(3), 1996, pp. 1209-1214
The present study describes the binding to human platelet A(2A) adenos
ine receptors of the new potent and selective antagonist radioligand -
2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c] pyrimidine ([H-3]SCH
58261). Saturation experiments revealed that [H-3]SCH 58261 labels a
single class of recognition sites with high affinity (K-d = 0.85 nM),
limited capacity (apparent B-max = 85 fmol/mg of protein) and good spe
cific binding (about 60%). [H-3]SCH 58261 binding was not modulated by
either the divalent cation Mg++ or guanine nucleotides. In competitio
n experiments, a series of both adenosine agonists and antagonists inh
ibited [H-3]SCH 58261 binding to A(2A) platelet receptors with rank or
der of potency and affinity similar to those observed in rat striatal
membranes with the same radioligand. This confirms that the platelet A
(2A) receptor is similar to that labeled in the brain striatum. Bindin
g data were also found to be in good agreement with the results from f
unctional studies such as A(2A) agonist-induced stimulation of adenyla
te cyclase or platelet aggregation inhibition. The present findings in
dicate that [H-3]SCH 58261 is the first radioligand available for the
characterization of the A(2A) receptor subtype in platelets.