Abstract

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.