Cloned and transfected P2Y(4) receptors: Characterization of a suramin and PPADS-insensitive response to UTP

The P2Y family of receptors are G protein-coupled receptors for ATP, ADP, UTP and UDP. Recently several members of this family have been cloned, including the P2Y(4), which is activated by UTP but not by ATP. In the present report, using receptors stably transfected into 1321N1 cells, we show that suramin acts as an antagonist at cloned P2Y(1) and (less potently) P2Y(2) receptors, but not at the cloned P2Y(4) receptor. Furthermore, PPADS (pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid), a potent antagonist at the P2Y(1) receptor, is a relatively inneffective antagonist at the cloned P2Y(4) receptor. This work moves us closer to the goal of classifying the native P2Y receptors on the basis of agonist and antagonist profiles.