EVIDENCE THAT THE P2Y3 RECEPTOR IS THE AVIAN HOMOLOG OF THE MAMMALIANP2Y(6) RECEPTOR

A P2Y receptor with 65% identity to mammalian P2Y(6) receptors, termed the p2y3 receptor, was recently cloned from a chick brain cDNA librar y and was proposed to represent a novel P2Y receptor subtype [Mol Phar macol 50:258-265 (1996)]. We cloned the turkey homologue of the chick p2y3 receptor, which shares hjgh sequence identity (97.6%) with the ch ick receptor, and we stably expressed this receptor and the rat P2Y, r eceptor in 1321N1 human astrocytoma cells. The capacities of uridine a nd adenine nucleotides to promote inositol phosphate accumulation and intracellular Ca2+ mobilization were determined for both receptors. UD P and 5-bromo-UDP were the most potent agonists and UTP was a less pot ent full agonist at both receptors. In contrast, adenine nucleotides a nd nucleotide derivatives were relatively more potent at the turkey p2 y3 receptor than at the rat P2Y(6) receptor. To determine whether the avian p2y3 receptor defined a new subtype of mammalian P2Y receptor or was a species homologue of the mammalian P2Y(6) receptor, we screened two different human genomic libraries and a Southern blot with a p2y3 receptor probe, under low-stringency conditions that allowed the clea r identification of the human P2Y(6) receptor gene. Our data indicated that the human genome does not contain a receptor that is more homolo gous to the avian p2y3 receptor than the P2Y(6) receptor. Taken togeth er, these data further define the pharmacological selectivities of the se UDP-selective receptors and strongly suggest that the avian p2y3 re ceptor is a species homologue of the mammalian P2Y(6) receptor.