RT Journal Article SR Electronic T1 Evidence that the p2y3 Receptor Is the Avian Homologue of the Mammalian P2Y6 Receptor JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 541 OP 546 DO 10.1124/mol.54.3.541 VO 54 IS 3 A1 Qing Li A1 Melanie Olesky A1 R. Kyle Palmer A1 T. Kendall Harden A1 Robert A. Nicholas YR 1998 UL http://molpharm.aspetjournals.org/content/54/3/541.abstract AB A P2Y receptor with 65% identity to mammalian P2Y6receptors, termed the p2y3 receptor, was recently cloned from a chick brain cDNA library and was proposed to represent a novel P2Y receptor subtype [Mol Pharmacol 50:258–265 (1996)]. We cloned the turkey homologue of the chick p2y3 receptor, which shares high sequence identity (97.6%) with the chick receptor, and we stably expressed this receptor and the rat P2Y6 receptor in 1321N1 human astrocytoma cells. The capacities of uridine and adenine nucleotides to promote inositol phosphate accumulation and intracellular Ca2+ mobilization were determined for both receptors. UDP and 5-bromo-UDP were the most potent agonists and UTP was a less potent full agonist at both receptors. In contrast, adenine nucleotides and nucleotide derivatives were relatively more potent at the turkey p2y3 receptor than at the rat P2Y6 receptor. To determine whether the avian p2y3 receptor defined a new subtype of mammalian P2Y receptor or was a species homologue of the mammalian P2Y6 receptor, we screened two different human genomic libraries and a Southern blot with a p2y3 receptor probe, under low-stringency conditions that allowed the clear identification of the human P2Y6 receptor gene. Our data indicated that the human genome does not contain a receptor that is more homologous to the avian p2y3 receptor than the P2Y6 receptor. Taken together, these data further define the pharmacological selectivities of these UDP-selective receptors and strongly suggest that the avian p2y3 receptor is a species homologue of the mammalian P2Y6receptor.