1 The human P2Y(11) receptor is coupled to both the phosphoinositide and th
e cyclic AMP pathways. A pharmacological characterization of the recombinan
t human P2Y(11) receptor has been conducted following stable expression in
two different cell lines: the 1321N1 astrocytoma cells for inositol trispho
sphate measurements and the CHO-K1 cells for cyclic AMP assays. The rank or
der of potency of a series of nucleotides was almost identical for the two
pathways: ATP gamma S approximate to BzATP > dATP > ATP > ADP beta S > 2MeS
ATP.
2 ADP beta S, AMP alpha S and A3P5PS behaved as partial agonists of the hum
an P2Y(11) receptor. At high concentrations, these three nucleotides were a
ble to partially inhibit the ATP response.
3 Suramin was a more potent antagonist than reactive blue 2, whereas pyrido
xal-phosphate-6-azophenyl-2',4'-disulphonic acid was completely inactive. T
he P2Y(11) receptor proved to be sensitive to suramin in a competitive way
with an apparent K-i value of 0.82 +/- 0.07 mu M.
4 The ATP derivative AR-C67085 (2-propylthio-beta, gamma-dichloromethylene-
D-ATP), a potent inhibitor of ADP-induced platelet aggregation, was the mos
t potent agonist of the P2Y(11) receptor, among the various nucleotides tes
ted.
5 The pharmacological profile of the recombinant human P2Y(11) receptor is
closely similar to that of the cyclic AMP-coupled Pt receptor recently desc
ribed in HL-60 cells, suggesting that it is the same receptor.