A family of G protein-coupled P2Y receptors that are activated by adenine and uridine nucleotides has been identified recently, Degenerate primers based on conserved sequences in these P2Y receptors were used to amplify turkey DNA, which was used to isolate the complete coding sequence of a cDNA that encodes a novel G protein-coupled receptor, Stable expression of this avian cDNA in 1321N1 human astrocytoma cells resulted in the conveyance of marked inositol phosphate responses to various nucleotides. Although this cloned avian receptor exhibited its highest homology to the previously cloned mammalian P2Y(4) receptor, ifs pharmacological selectivity was not consistent with the avian receptor's being a species homologue of the P2Y(4) receptor, That is, whereas the P2Y(4) receptor is selectively activated by UTP and is not activated by ATP or A(P4)A, the novel avian receptor was potently activated by ATP and A(P4)A as well as by UTP. Taken together, these results describe the identification of an avian phospholipase C-coupled P2Y receptor that, like the mammalian P2Y(2) receptor, is activated by both adenine and uridine nucleotides.